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Volume 1 Issue 2 www.ijrpb.com March-April 2013
Indian Journal of Research in Pharmacy and Biotechnology
ISSN: 2320-3471 (Online)
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Nimra College of Pharmacy
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Nimra College of Pharmacy
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Editorial Advisory Board
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Volume 1 Issue 2 www.ijrpb.com March-April 2013
ISSN: 2320-3471 (Online)
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ISSN: 2320 – 3471(Online)
Volume 1 Issue2 www.ijrpb.com March –April 2013
Contents Page
Nos.
Antidepressant activity of ethanolic extract of plant Kalanchoe pinnata (lam) pers in mice
Shashank Matthew, Ajay Kumar Jain, Cathrin Matthew, M.Kumar, Debjit Bhowmik
153-155
Antinociceptive and anti-inflammatory activity of Tecoma stans leaf extracts
V Lakshmi Prasanna, K Lakshman, Medha M Hegde and Vinutha Bhat
156-160
Recent trends in usage of polymers in the formulation of dermatological gels
Shaik Arif Bhasha, Syed Abdul Khalid, S.Duraivel, Debjit Bhowmik, K.P.Samapth Kumar
161-168
Recent trends of polymer usage in the formulation of orodispersible tablets
J.Preethi, MD Farhana, B.Chelli Babu, MD.Faizulla, Debjit Bhowmik, S.Duraivel
169-174
Design and development of amlodipine besylate fast dissolving tablets by using natural
superdisintegrants
N.Narasimha Rao, B.Radha Krishna Murthy, D.Rajasekhar, P. Suri Babu, K. Phaneendra Babu,
Srinivasa Babu. P
175-179
Formulation optimization and evaluation of liposomal gel of prednisolone by applying
statistical design
Varde Neha M, Thakor Namita M, C.Sini Srendran, Shah Viral H
180-187
ADR monitoring in hypertension outpatient department of hospital
Sreenu Thalla, K.Venkatta Ramana, Sk.Sheherbanu, Sk.Ashya, A.Manikanteswara Reddy,
B.Lakshmi
188-190
Evaluation of the antioxidant and hepatoprotective activity of Madhuca longifolia (koenig)
leaves
Arun Kumar, Kaushik Biswas, S Ramachandra Setty
191-196
Formulation and evaluation of sustained release matrix tablets of Metformin hydrhocloride
A Madhusudhan Reddy, Ayesha Siddika, P Surya Bhaskara Rao,
197-200
Herbal medicine
Atheeq-ur-Rahman, Ismail Shaik , K.P.Samapth Kumar
201-205
Microsponge drug delivery system
SK Shafi, S.Duraivel, Debjit Bhowmik, K.P.Sampath Kumar
206-209
Nanotherapeutics – an era of drug delivery system in nanoscience
Bhargavi, Ch.Anil, Debjit Bhowmik, Praneta Desale, K.P.Sampath Kumar
210-214
A validated RP-HPLC method for the estimation of Baclofen in bulk drug and pharmaceutical
formulations
Rajesh M, Manzoor Ahmed, Maanasa Rajan BN
215-218
A validated RP-HPLC method for the estimation of Cisapride in bulk drug and pharmaceutical
formulations
Maanasa Rajan.B.N, Manzoor Ahmd, Rajesh M
219-222
Review article on antimicrobial resistance
Maryam Bincy Thomas, Suruchi Singh
223-225
Urinary tract infection: causes, symptoms, diagnosis and it’s management
M. Komala, K.P.Sampath Kumar
226-233
Diabetes epidemic in India: risk factors, symptoms and treatment
Abhinov T, Md Aasif Siddique Ahmed Khan, Ashrafa, Shabana Parveen, K.P.Samapth Kumar
234-243
Simultaneous estimation of Olmesartan and Atorvastatin in bulk and fromulation by using UV
spectroscopy and RP-HPLC
Revanth Reddy B, Aravind G
244-254
Development and validation of RP-HPLC method for the determination of Cefdinir in bulk and
capsule dosage form
P.Ravisankar, G.DevalaRao, M.KrishnaChaitanya
255-263
Simultaneous separation of six Fluoroquinolones using an isocratic hplc system with uv
detection: application to analysis of levofloxacin in pharmaceutical formulations
Ravisankar Panchumarthy, Devala Rao Garikapati, Krishna Chaitanya Manukonda, Sandhya Rani
Nagabhairava
264-274

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Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April 2013 Page 153
ANTIDEPRESSANT ACTIVITY OF ETHANOLIC EXTRACT OF PLANT
KALANCHOE PINNATA (LAM) PERS IN MICE
Shashank Matthew1
*, Ajay Kumar Jain2
, Cathrin Matthew2
, M.Kumar3
, Debjit Bhowmik4
1. Department of Pharmaceutical Sciences, Sardar Patel College of technology, Balaghat
2. Government district hospital, Balaghat
3. Vinayaka missions college of Pharmacy, Salem
4. Karpagam University, Coimbatore
* Corresponding author: Email: sheak1980@gmail.com
ABSTRACT
The main objective of present work is to find out good pharmacological activities in herbal source
with their preliminary phytochemical study, and also it is aimed to investigate anti-diabetic activity of
ethenolic and aqueous extracts of dried stem of plant Kalanchoe pinnata (LAM)PERS against CNS-
Depressant activity in rats. Normally herbal products are free from side effects/adverse effects and they are
low cost medicines, which will be beneficial for human being. The main objective of this work is to develop
potent CNS-Depressant agent having no or minimum side effects from indigenous plants for the therapeutic
management.
KEYWORDS: Phytochemical study, Kalanchoe pinnata,
1. INTRODUCTION
The World Health Organization (WHO) defined health as “a complete state of physical, mental, and
social well-being and not merely the absence of disease or infirmity”. So during the past decade, traditional
systems of medicine have become a topic of global importance. Current estimate suggest that, in many developing
countries a large proportion of the population relies heavily on traditional practitioners and medicinal plants to
meet primary health care needs. Although modern medicine may be available in these countries, herbal medicines
(phytomedicines) have often maintained popularity for historical and cultural reasons. Concurrently, many people
in developed countries have begun to turn to alternative or complementary therapies, including medicinal herbs.
2. MATERIAL AND METHODS
2.1. Collection and authentication of plant material: The specimen copy (Herbarium) of selected plant
collected in month of july-2007 from ABS Botanical garden, Karripatty, Distt. - Salem, Tamil Nadu Mr.A.
Balsubramnian, (Consultant-central siddha research) Executive Director ABS botanical garden, Salem,
authenticated the plant as Kalanchoe Pinnata (LAM) PERS (Family- Crassulaceae).
2.2. Preparation of extract: The stem of Kalanchoe Pinnata (LAM) PERS were dried under shade and then
powdered with a mechanical grinder. The powder was passed through sieve No. 30 and stored in an airtight
container for further use.
2.3. Solvent for extraction:
• Petroleum Ether (60-80o
C)
• Alcohol (95% v/v)
• Distilled water with chloroform (0.25%)
2.4. Extraction procedure: The dried powders of stem of Kalanchoe pinnata were defatted with petroleum ether
(60-80ºc) in a Soxhlet Apparatus by continuous hot- percolation. The defatted powder material (marc) thus
obtained was Further extracted with ethanol (95% v/v) with same method and fresh powder used for aqueous
extraction by Cold maceration method. The solvent was removed by distillation under low pressure and
evaporation. The resulting semisolid mass was vacuum dried by using rotary flash evaporator. The resultant dried
extracts were used for further study.
2.5. Procurement of experimental animals: Swiss albino mice (20-25 g) and albino Wister rats (150-200 g) of
either sex and of approximate same age are used in the present studies were procured from listed suppliers of Sri
Venkateswara Enterprises, Bangalore, India. The animals were fed with standard pellet diet (Hindustan lever Ltd.
Bangalore) and water ad libitum. All the animals were housed in polypropylene cages. The animals were kept
under alternate cycle of 12 hours of darkness and light. The animals were acclimatized to the laboratory condition
for 1 week before starting the experiment. The animals were fasted for at least 12 hours before the onset of each
activity. The experimental protocols were approved by Institutional Animal Ethics Committee (IAEC No.-P.Col. /
/2007) after scrutinization. The animals received the drug treatments by oral gavage tube.
2.6. CNS- depressant activity: Most of the central nervous system acting drugs influence the locomotor activities
in man and animals. The CNS - Depressant drugs such as barbiturates and alcohols reduce the motor activity,

while the stimulants such as caffeine and amphetamine increase the activity, in other words, the locomotor
activity can be an index of wakefulness (alertness) of mental activity. In the present study the attempt has been
focused to evaluate the CNS-Depressant activity of extracts of stem of plant Kalanchoe pinnata (LAM) PERS on
the locomotor activity of mice using actophotometer.
Table.1. Treatment design
Group I Normal control (Normal saline 0.9%)
Group II Positive control (Chlorpromazine 3 mg / kg i.p.)
Group III Ethanolic extract (300mg / kg)
Group IV Ethanolic extract (600mg / kg)
Group V Aqueous extract (300mg / kg)
Group VI Aqueous extract (600mg / kg)
Procedure:-
1. Albino mice weighing between 150-200 gm was purchased from Venkateshwara Enterprises,
Bangalore
2. Animals are divided into 6 groups.
3. The equipment was turned on and each animal are placed in activity cage and for 10 min. and the
basal activity score is noted down.
4. Normal saline is administrated in the dose of 2 ml / kg to the first group (normal control).
5. Chlorpromazine (3mg / kg) was administered to II group of animal.
6. The animals of group III, IV, were treated with ethanolic extracts and V, VI with aqueous extracts.
7. After 45 min of the treatment, once again the animals were placed in the activity cage and the score
was noted. The difference in the activity before and after treatment was noted. The percent decrease
in motor activity was calculated and compared with control group of animals (Kulkarni, S. K- 2005).
8. CNS -- Depressant activity of alcoholic and aqueous extract of dried stem of plant kalanchoe pinnata
(LAM.)PERS., on the locomotor activity of mice using actophotometer.
Table 2. Evaluations of CNS-depressant activity
Group Treatment design Dose Locomotor activity in 10mins. % decrease
in activityBefore treatment after treatment
1 Normal control 2ml/kg 224.5 ± 1.88 220.5 ± 1.75 -----
2
Standard
(Chlorpromazine)
3mg/kg 280.33 ± 0.55* * 106.00 ± 1.03* * 62.18
3 Ethanolic extract 300mg/kg 216.83 ± 0.74* * 110.16 ± 0.65* * 49.19
4 Ethanolic extract 600mg/kg 209.00 ± 0.57* * 94.8 ± 0.83* * 54.62
5 Aqueous extract 300mg/kg 223.00 ± 0.41 170.00 ± 1.53* * 23.76
6 Aqueous extract 600mg/kg 229.160 ± 0.98* * 176.5 ± 1.89* * 32.98
Values are expressed by Mean ± SEM P values: * * P< 0.01; * P <0.05. One way ANOVA followed by
DUNNETT’S, multiple comparison tests
3. CONCLUSION
Alcoholic extract of plant Kalanchoe pinnata (LAM) PERS have more CNS-depressant activity as
compared to aqueous extract but as compare to standard drug it shows near about same action.
REFERENCES
Dhanurkar RA, Kulkarni NN, Pharmacology of medicinal plants and natural products, Ind J
Pharmacology, 32, 2000, 81-118.
Gupta SS, Prospects and perspective of natural plant products in medicine, Indian J of pharmacology
1994, 26, 1-12.
John AO, Ojewole, Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum
pinnatum (Crassulaceae) leaf aqueous extract, Journal of Ethnopharmacology 99, 1, 13-19.

Joshi Shashank R, Shah Siddhart N, Rising global burden of Diabetes, The Asian J of Diabetology,
1(3), 1999, 13-15.
Lenzen S, and Munday R, Thiol-group reactivity, hydrophilicity and stability of alloxan, its
reduction products and its N-methyl derivatives and a comparison with ninhydrin, Biochemical
Pharmacology, 42, 1991, 1385-1391.
Lenzen S, Panten U, Alloxan: history and mechanism of action, Diabetologia, 31, 1988, 337-342.
Lipnick RL, Cotruvo JA, Hill RN, Comparison of the up and down method and the fixed dose
procedure acute toxicity procedures, Fd Chen, Toxic, 33, 1995, 223-231.
Pincus I J, Hurwitz, Scott M E, effect of rate of injection of alloxan on development of diabetes in
Rabbits, J Am Physio Soc, 86, 1954, 553-555.
Ramachandran A, Snehlata C, Viswanthan V, burden of type 2 Diabetes and its complications, The
Indian scenario, Current science, 83, 2002, 1471-1476.
Salahdeen HM and Yemitan OK, Neuropharmacological effects of aqueous leaf extract of
Bryophyllum Pinnatum in mice, African journal of biomedical research, 9, 2006, 101-107.
Shukla R, Sharma S B, Puri D, Prabhu M K, and Murth P S, Medicinal plants useful in diabetes,
Indian J Clinic Biochem, 15, 2002, 169.
Siddharta P, Chaudhuri AKN, Further studies on the anti-inflammatory profile of the methanolic
fraction of the fresh leaf extract of Bryouphyllum pinnatum, Fitoterapia, 63(5), 1992, 451-459.
V Babu, Gangadevi T, Subramonian A, Antihyperglycemic activity of cassia Kleinl leaf extract in
glucose fed normal rats and alloxan induced diabetic rats; Indian Journal of Pharmacology 2002, 34,
409-415.

V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
ANTINOCICEPTIVE AND ANTI-INFLAMMATORY ACTIVITY OF TECOMA
STANS LEAF EXTRACTS
V Lakshmi Prasanna1
*, K Lakshman2
, Medha M Hegde2
and Vinutha Bhat2
1.Department of Pharmacognosy, Creative Educational Society’s College of Pharmacy, Kurnool. A.P.
2. Department of Pharmacognosy, PES College of Pharmacy, Bangalore, Karnataka.
*Corresponding author: E-mail:vlakshmi.prasanna.14@gmail.com
ABSTRACT
Tecoma stans (Bignoniaceae) is used in the treatment of diabetes, stomach pains,
rheumatism, diuretic, vermifuge and tonic in traditional medicine. The present study has been
design to evaluate antinociceptive and anti-inflammatory activities of alcohol and aqueous
extracts of Tecoma stans leaves and to determine total phenolic and flavonoid contents. Both
extracts shows dose dependent activity. The antinociceptive activity was investigated using hot
plate, acetic acid induced writhing and formalin induced paw licking methods. Anti-inflammatory
activity was evaluated using carrageenan induced paw oedema method. Total phenolic and
flavonoid content determined using standard chemical methods. Alcohol extract (500 mg/kg)
showed highest 76.92% inhibition of inflammation after 24 hrs. Both the extracts produced
increased in latency time compared to vehicle but alcohol extract showed highest activity after
150 min in hot plate method (4.63 ± 0.08 sec) and inhibit nocipeptive response in both phase.
Extracts also produced significant inhibition of writhing. Content of total phenolic and flavonoid
also found more in alcoholic extract. These findings demonstrate that the alcohol leaf extract of
Tecoma stans have excellent antinociceptive and anti-inflammatory activity, which may due to
presence of higher phenolic and flavonoid content.
Key-words: Tecoma stans leaves; antinociceptive; anti-inflammatory; phenolic content; flavonoid content.
1. INTRODUCTION
Tecoma stans (Bignoniaceae) is a fast growing small evergreen shrub tree, that grows to a height of
7.5meters. Leaves are compound and imparipinnate with 2 to 5 pairs of leaflets. Flowers occur in clusters at the
ends of the branches and are trumpet shaped with 5 rounded lobes, 6 cm long, pale to bright yellow in color.
Fruits are narrow, slightly flattened to pointed capsules, up to 20 cm long (Orwa C, 2009). The chemical
constituents of Tecoma stans are triterpenes, hydrocarbons, resins, volatile oil. Leaves and stems contain
flavonoids, chrysoeriol, luteolin, hyperoside, indole oxygenase. Alkaloids like tecomanine, tecostanine, 4-
noractinidine, 4-norskytanthine and boschniakine. Flowers contain β-carotene and Zeaxanthin. Roots are used as
vermifuge, diuretic, tonic (Yoganarasimhan, 1904).
The leaves are claimed to be useful in the treatment of inflammation and pain. Even though, Tecoma
stans was reported to be useful in many ailments, there are no reports regarding its antinociceptive and anti-
inflammatory activity. Hence in the current study, the anti-inflammatory and antinociceptive activity of alcohol
and aqueous extracts of Tecoma stans leaves was studied using different animal models. This study is a scientific
approach to validate the traditional use of the leaves of Tecoma Stans.
2. MATERIALS AND METHODS
2.1. Plant material: Dried leaves of Tecoma stans (Bignoniaceae) were collected from GKVK and authenticated
by Dr.Rajanna from GKVK, Bangalore. A voucher specimen has been deposited at departmental herbarium for
future reference (TS-10-03).The plant material was dried, powdered and stored in air tight containers for further
studies. The powdered material weighing 500 g was extracted by Soxhlet using alcohol and water. The solvent
was completely removed by using a rotary flash evaporator to get a semisolid mass. The Alcohol and aqueous
extract yield is 10.80 and 21.75% W/W.
2.2. Animals: Albino mice and Wistar rats of either sex weighing 18-24 g and 150-200 g respectively, housed
under standardized animal house conditions were used in all the experiments. They had access to standard pellet
and water ad libitum. Animals were divided into six groups of six each. All the experiments are approved by
Institutional Animal Ethics Committee, PES College of Pharmacy, India.
2.3. Preliminary phytochemical studies: Alcoholic & aqueous extracts of Tecoma stans were investigated for
qualitative chemical examination which gives an idea regarding the chemical constituents present in the extracts.
Phytochemical screening was done as explained in literature (Ikhiri, 1992).

2.4. Determination of total phenolic content: The amount of phenol in the alcohol and aqueous leaf extract of
Tecoma stans was determined with Folin-Ciocalteu reagent using the method (Olayinka A Aiyegoro, Anthony I
Okoh, 2010). Gallic acid (0-0.5 mg/ml) was used as standard and results were expressed as mg/g gallic acid
equivalent of dry extract.
2.5. Estimation of total flavonoids: Aluminum chloride colorimetric method was used for flavonoids
determination (Hole K, Hunskaar S, 1987). The content was determined from extrapolation of calibration curve
which was made by preparing quercetin solution (0-0.8 mg/ml) in distilled water. The concentration of flavonoid
was expressed in terms of mg/g quercetine equivalent.
2.6. Antinociceptive activity
2.6.1. Hot plate method: The animals were placed on Eddy's hot plate maintained at a temperature of 55 ± 0.5°C.
A cut-off period of 15 s was observed to avoid damage to the paw. Reaction time and the type of response were
noted using a stopwatch. The response is in the form of jumping, withdrawal of the paws or the licking of the
paws. Pentazocine was used as standard (10 mg/kg) which was administered i.p. The alcohol and aqueous extracts
of Tecoma stans (250 and 500 mg/kg) were administered orally (Koster R, 1959). The response was observed at
0, 30, 60, 120 and 150 min.
2.6.2. Formalin induced paw licking model: One hour after oral administration of test compounds (250 and 500
mg/kg alcohol and aqueous extracts of Tecoma stans), 20 µl of 1% formalin was injected into the paw of each
animal. Duration of paw licking was monitored 0-5min (first phase) and 15-30min (second phase) after formalin
injection. Pentazocine was used as a standard (10mg/kg) which was administered i.p (Winter CA, 1962).
2.6.3. Acetic acid induced writhing test: Albino mice were administered with different treatments orally one
hour before acetic acid injection. Control group received only vehicle, and animals under standard group received
Diclofenac sodium (10 mg/kg, p.o.). One hour after drug administration, 1% v/v acetic acid (0.1ml/10 g, i.p.) was
injected. Five minutes after the intraperitoneal injection of acetic acid, number of writhing were counted for the
period of 20 minutes (Ahamed KN, 2005).
2.7. Anti-inflammatory activity
2.7.1. Carrageenan-induced rat paw edema: Acute inflammation was produced by injecting 0.1ml of (1%)
carrageenan (in a normal saline solution) into plantar surface of rat hind paw. The alcohol and aqueous extracts
(250 and 500 mg/kg, orally), Diclofenac sodium (10 mg/kg, orally) as a reference agent were administered 60min
before carrageenan injection. The paw edema volume was recorded using a plethysmometer at a different time
intervals (Tjolsen A, 1992).
2.7.2. Statistical analysis: The results and data obtained in this study were evaluated using one-way analysis of
variance (ANOVA) followed by Dunnett’s multiple comparison test. The values are expressed as mean + SEM
and p < 0.05 was considered significant.
3. RESULTS
3.1. Preliminary phytochemical analysis: Our qualitative preliminary phytochemical tests showed the presence
of alkaloids, glycosides, saponins, phenols, tannins, proteins, carbohydrates, phytosterols in alcoholic extract of
Tecoma stans, and aqueous extract of the plant showed similar constituents positive except phyosterols, while
fixed oils & fats are absent in both the extracts.
3.2. Total phenolic and total flavonoid content: The total phenolic & flavonoid content is more in alcohol
extract (72.3 mg/g GAE and 49.6 mg/g QE) than aqueous extract (64.2 mg/g GAE and 38.5 mg/g QE) (Table 1).
Table 1: Presence of total phenolic and flavonoid content in the extracts
Extract Total phenolic content
(mg/g gallic acid equivalent)
Total flavonoid content
(mg/g quercetine equivalent)
Alcohol extract 72.3±1.23 49.6±0.99
Aqueous extract 64.2±1.02 38.5±0.80
Results were expressed as mean±SEM (n=3).
3.3. Antinociceptive activity: The extracts of Tecoma stans has shown significant dose dependent
antinociceptive activity, however the alcohol extract (500 mg/kg) produced better activity than the aqueous
extract. The alcohol extract (500 mg/kg) showed highest activity after 150 min in hot plate method as latency time
increases to 4.63 ± 0.08 sec after 150 min compare to 1.08 ± 0.08 of control (Table 2).

Table 2: Effect of alcohol and aqueous leaf extract of Tecoma stans on Hot plate model
Treatment Dose(mg/kg) Initial 30min 60min 120min 150min
Control 10 1.02±0.09 0.94±0.05 1.16±0.07 1.27±0.01 1.08±0.08
Pentazocine 10 1.14±0.04 2.42±0.19*** 4.06±0.03*** 5.36±0.08*** 5.80±0.06***
Alcohol extract 250 0.97±0.01 1.08±0.05 1.94±0.01*** 2.62±0.06*** 3.26±0.03***
Alcohol extract 500 0.93±0.04 1.17±0.01* 2.69±0.04*** 3.74±0.07*** 4.63±0.08***
Aqueous extract 250 1.01±0.02 1.09±0.05 1.18±0.01 2.10±0.01*** 2.35±0.06***
Aqueous extract 500 0.95±0.07 1.15±0.02* 2.06±0.03*** 3.17±0.07*** 3.98±0.03***
Values are mean ± SE, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by
Dunnett’s test.
Oral administration of alcohol extract (250 and 500 mg/kg) produced inhibition of 28.48% and 37.43% pain
response in first phase and inhibition of 53.41% and 74.56% paw licking response in second phase. Aqueous
extract produce comparatively less effect than the alcohol extract and produced inhibition of 23.98% and 29.73%
pain response in first phase and inhibition of 40.33% and 59.46% pain response in second phase at a dose of 250
mg and 500 mg/kg respectively (Table 3).
Table 3. Effect of alcohol and aqueous leaf extract of Tecoma stans on Formalin induced paw licking model
Treatment Dose
mg/kg
%inhibition of Paw licking in
early phase 0-5min
%inhibition of Paw licking in
late phase 15-30min
Control 10 - -
Pentazocine 10 47** 80.22***
Alcohol extract 250 28.48* 53.41***
Alcohol extract 500 37.43** 74.56***
Aqueous extract 250 23.98 40.33***
Aqueous extract 500 29.73* 59.46***
Values are mean ± SE, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by
Dunnett’s test.
Alcohol extract produced 36.5% and 53.5% inhibition of writhing response in low and high dose respectively.
Aqueous extract has produced less inhibition than the alcohol extract (Table 4).
Table 4: effect of alcohol and aqueous leaf extract of Tecoma stanus on acetic acid induced writhing model
Treatment Dose (mg/kg) Number of writhing % inhibition
Control 70.5
Diclofenac sodium 3 25.8 63.4***
Alcohol extract 250 44.7 36.5**
Alcohol extract 500 32.9 53.3***
Aqueous extract 250 50.2 28.7*
3.4. Anti-inflammatory activity: The test extracts at doses of 250 and 500 mg/kg as well as diclofenac sodium
(10 mg/kg), showed significant inhibition of edema in dose dependent manner 3 h after carrageenan-induced
inflammation, when compared with the control. Both alcohol extract and aqueous extract of Tecoma stans
produced dose dependent inhibition of paw edema, The percentage inhibition of edema was 63.3%, 76.92%,
57.05% and 64.74% against alcohol extract (250 mg/kg and 500 mg/kg) and aqueous extract (250 mg/kg and 500
mg/kg) respectively after 24h (Table 5).

Table 5: Effect of alcohol and aqueous leaf extract of Tecoma stans on Carrageenan induced rat paw edema
model.
Treatment Dose (mg/kg) % inhibition of paw edema
Inflammation
3h 24h
Control - 0.00 0.00
Diclofenac sodium 10 35.60*** 79.48***
Alcohol extract 250 23.48 63.34***
Alcohol extract 500 30.06*** 76.92***
Values are mean ± SEM, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by
Dunnett’s test.
4. DISCUSSION
Both the extracts showed activity in a dose dependent manner. The alcohol extracts showed potent
antinociceptive and anti-inflammatory activity compare to aqueous extract. The hot plate test is considered to be
selective for opioid like compounds, which are centrally acting analgesic in several animal species. The hot plate
method has been found to be suitable for evaluation of centrally acting analgesic (Shibata, 1989).The alcoholic
and aqueous extracts at low and high doses (250 and 500 mg/kg) increase the reaction time in dose dependent
manner to the thermal stimulus. The highest antinociception of thermal stimulus was exhibited at higher dose of
alcohol extract than aqueous extract. This could be the possible explanation for its central analgesic activity
observed in hot plate test.
The formalin induced paw licking test is a valid and reliable model for analgesic activity and it is
sensitive for various classes of analgesic drugs. Formalin test produces a distinct biphasic response and different
analgesics may act differently in the early and late phases of this test. Therefore, the test can be used to clarify the
possible mechanism of the antinociceptive effect of a proposed analgesic (Rosland, 1990). Centrally acting drugs
such as opioids inhibit both phases equally (Taesotikul, 2003). But peripherally acting drugs such aspirin;
indomethacin and dexamethasone only inhibit the late phase. The late phase seems to be anti inflammatory
response with inflammatory pain that can be inhibited by anti-inflammatory drugs (Marsha, 2002). The alcoholic
and aqueous extracts exhibited a significant antinociception in both early and late phase of the formalin test.
Acetic acid induced writhing test, a model of chemo-nociception and it induced pain by increasing fluids
of PGE2 and PGE2α. Acetic acid also induces sympathetic nervous system mediators, which are found in high
level at first 30 min after acetic acid injection. This probably indicates that the analgesic activity of the extracts
was mediated by inflammatory as well as neurogenic mechanisms. The alcohol and aqueous extract exhibited
significant, dose-dependent decrease in the number of abdominal constrictions. However alcohol extract has
shown good activity compare to aqueous extract.
Carrageenan induced paw edema is characterized by a biphasic events, with involvement of different
inflammatory mediators (Marsha KMG, 2002). In first phase (during the first 2h after carrageenan injection)
chemical mediators such as histamines and serotonin play a role (Marsha, 2002) while in second phase (3-5h)
after carrageenan infection kinin and prostaglandins are also released. Administration of alcohol extract at 250
and 500 mg/kg inhibited the edema from the 3h after carrageenan challenge, and aqueous extract at dose of 250
and 500 mg/kg inhibited the edema from 4h after carrageenan challenge, which probably inhibits the different
aspects and chemical mediators of inflammation.
The phytochemical analysis of various extracts showed the presence of carbohydrates, alkaloids,
glycosides, tannins, saponins, phytosterols, phenolic compounds, proteins, amino acids, flavonoids, gums and
mucilage. Our result also showed that extract contain significant amount of total phenolic and flavonoid content.
The anti-inflammatory effect of Tecoma stans may be due to the presence of flavonoids. It has been reported that
flavonoids possess anti-inflammatory and analgesic activity. Flavonoids are known to target prostaglandins which
are involved in the late phase of acute inflammation and pain perception. Hence, the presence of flavonoids may
be contributory to the anti-inflammatory and analgesic activities of Tecoma stans.
This study confirms the antinociceptive and anti-inflammatory activity of leaves of Tecoma stans. Both activities
were found to be comparable with reference drug. Further studies need to be done to identify and separate the

group of active constituents responsible for antinociceptive and anti-inflammatory activity from alcohol and
aqueous extracts.
ACKNOWLEDGEMENT
Authors are thankful to the Management, Director, Principal, Dr.S.Mohan, PES college of Pharmacy for
providing necessary facilities to carry out this work & Dr.Rajanna, GKVK, Bangalore, for identifying the plant.
REFERENCES
Ahamed KN, Kumar V, Raja S, Mukherjee K, Mukherjee PK. Anti- nociceptive and anti- inflammatory
activity of Araucaria bidwilli Hook, IJPT, 1, 2005, 105-109.
Hole K, Hunskaar S, The formalin test in mice dissociation between inflammatory and non inflammatory
pain. Pain, 30, 1987, 103-111.
Ikhiri K, Boureima D, Dan-Kouloudo D. Chemical screening of medicinal plants used in traditional
pharmacopoeia of Niger, Int J Pharmacog, 30, 1992, 251–262.
Koster R, Anderson M, De-Beer EJ, Acetic acid analgesic screen Fed Proc Fed Am Soc Exp Biol, 18, 1959,
418-420.
Marsha KMG, Everton TA, Oswald SR. Preliminary investigation of the Anti-inflammatory properties of an
aqueous extract from Morinda citrifolia (Noni), Proc West Pharmacol Soc, 45, 2002, 76-78.
Olayinka A Aiyegoro, Anthony I Okoh, Preliminary phytochemical screening and In vitro antioxidant
activities of the aqueous extract of Helichrysum longifolium, BMC Complementary and Alternative Medicine,
10, 2010, 1472-6882.
Orwa C, Mutua A, Kindt R, Jamnadass R, Anthony S, Agroforestry Database:a tree reference and selection
guide version. Available at: http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp.2009,
Accessed on 14 June 2010.
Rosland JH, Tjoisen A, Maehle B, Hole K, The formalin test in mice: effect of formalin concentration. Pain,
1990, 42, 235.
Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test characteristic biphasic pain response.
Pain, 38, 1989, 347.
Taesotikul T, Panthong A, Kanjanapothi D, Verpoorte R, Scheffer JJC. Anti- inflammatory,antipyretic and
antinoceceptive activities of Tabernaemontaa pandacaqui Poir, J of Epharmacol, 84, 2003, 31-35.
Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K, The formalin test: an evaluation of the method. Pain,
51, 1992, 5.
Winter CA, Risley EA, Nuss GW, Carragenan induced edema in hind paw of the rat as assay for anti
inflammatory drugs, Proceedings of the society for experimental biology and medicine, 1962, 11, 544-547.
Yoganarasimhan SN, Medicinal plants of India, Bangalore, India, 10th
ed, Interline publisher pvt limited.
1904, 81.

Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
RECENT TRENDS IN USAGE OF POLYMERS IN THE FORMULATION OF
DERMATOLOGICAL GELS
Shaik Arif Bhasha1
, Syed Abdul Khalid1
, S.Duraivel1
, Debjit Bhowmik1
, K.P.Samapth Kumar2
*
1. Nimra college of pharmacy, Vijayawada, India
2. Department of Pharmaceutical Sciences, Coimbatore medical college, Coimbatore, India
Corresponding author: Email:debjit_cr@yahoo.com
ABSTRACT
Topical preparations can be applied directly to an external body surface by spreading, rubbing,
and spraying. The topical route of administration has been utilized either to produce local effect for
treating skin disorder or to produce systemic drug effects. Within the major group of semisolid
preparations, the use of transparent gels has expanded both in cosmetics and in pharmaceutical
preparations. Gels often provide a faster release of drug substance, independent of the water solubility of
the drug, as compared to creams and ointments. They are highly biocompatible with a lower risk of
inflammation or adverse reactions, easily applied and do not need to be removed. Gels for
dermatological use have several favorable properties such as being thixotropic, greaseless, easily
spreadable, easily removed, emollient, non-staining, and compatible with several excipients and water
soluble or miscile. Dosage form selection should include those delivery systems that are non-
comedogenic. Gels tend to be most effective as they have faster absorption than creams. Gels containing
only water tend to be slow to dry; so the addition of ethyl or isopropyl alcohol to the gel hastens their
drying to a film. But some patients may need the less drying lotions or creams for dry or sensitive skin or
for use during dry winter weather.
INTRODUCTION
Gels are semisolid systems in which a liquid phase is constrained within a three-dimensional polymeric
matrix (consisting of natural or synthetic gums) in which a high degree of physical (or sometimes chemical) cross-
linking has been introduced. Some of these systems are as clear as water in appearance, visually aesthetically
pleasing as in gelatin deserts and other are turbid. The clarity range is from clear to a whitish translucent. The
polymers are used between 0.5-15% and in most of the cases they are usually at the concentration between 0.5-2%.
Gels are usually clear, transparent, semisolids, containing the solubilised active substances (Lachman, 1987). The
term “Gel” was introduced in the late 1800 to name some semisolid material according to pharmacological, rather
then molecular criteria. The U.S.P. defines gels as a semisolid system consisting of dispersion made up of either
small inorganic particle or large organic molecule enclosing and interpenetrated by liquid. The inorganic particles
form a three-dimensional “house of cards” structure. Gels consist of two-phase system in which inorganic particles
are not dissolved but merely dispersed throughout the continuous phase and large organic particles are dissolved in
the continuous phase, randomly coiled in the flexible chains.
Advantages:
 Avoidance of first pass metabolism.
 Convenient and easy to apply.
 Avoidance of the risks and inconveniences of intravenous therapy and of the varied conditions of absorption,
like pH changes, presence of enzymes, gastric emptying time etc.
 Achievement of efficacy with lower total daily dosage of drug by continuous drug input.
 Avoids fluctuation in drug levels, inter- and intrapatient variations.
 Ability to easily terminate the medications, when needed.
 A relatively large area of application in comparison with buccal or nasal cavity
 Ability to deliver drug more selectively to a specific site.
 Avoidance of gastro-intestinal incompatibility.
 Providing utilization of drugs with short biological half-life, narrow therapeutic window.
 Improving physiological and pharmacological response.
 Improve patient compliance.
 Provide suitability for self-medication.
Disadvantages:
 Skin irritation of contact dermatitis may occur due to the drug and/or excipients.
 Poor permeability of some drugs through the skin.

 Possibility of allergenic reactions.
 Can be used only for drugs which require very small plasma concentration for action
 Enzyme in epidermis may denature the drugs.
 Drugs of larger particle size not easy to absorb through the skin.
Characteristics of gels:
1. Ideally gelling agents for pharmaceutical and cosmetic use should be inert, safe and nonreactive with other
formulation components. A potential incompatibility is illustrated by the combination of cationic drug, preservative
or surfactant with an anionic gel former. For example sodium alginate has been shown to reduce the concentration of
cationic preservatives in solution as well as complex with chlorpheniramine, reduce the drug release rate from gelled
formulation. Polyether has been shown to interact with phenols and carboxylic acids, leading to loss of potency.
2. The inclusion of a gelling agent in a formulation should provide a reasonable solid like nature during storage that
can be broken when subjected to the shear force generated in shaking a bottle, squeezing a tube, or during topical
application. A cost consideration requires a low concentration of gallant to produce the desired characteristics.
3. The gel should exhibit little viscosity change under the temperature variations of normal use and storage. For e.g.
plastic base exhibits a lesser decrease in consistency than petrolatum over the some temperature range. This
minimizes unacceptable changes in the products’ characteristics.
4. The gels particularly those of polysaccharide nature are susceptible to microbial degradation. Incorporation of a
suitable preservative may prevent contamination and subsequent loss of gel characteristics due to microbial attack.
5. The gel characteristics should match the intended use. A topical gel should not be tacky. Too high a concentration
of gel former or the use of an excessive molecular weight may produce a gel difficult to dispense or apply. An
ophthalmic gel must be sterile. The aim in to produce a stable elegant, economic gel product adequately suited for its
intended use.
6. Swelling: Gels can swell, absorbing liquid with an increase in volume (e.g. Xerogels). This is referred to as
swelling and the pressure developed is known as swelling pressure. The swelling can be looked on as the initial phase
of dissolution as osmosis occurs, where solvent penetrates the gel matrix. Gel-gel interactions are replaced by gel-
solvent interactions. Limited swelling is usually the result of some degree of cross linking in the gel matrix that
prevents total dissolution. Such gels swell considerably when the solvent mixture posses a solubility parameter
comparable to that of the gallant.
7. Syneresis: Many gels systems undergo a contraction upon standing. The interstitial liquid is expressed, collecting
at the surface of the gel. This process is referred to as syneresis or bleeding. Syneresis is not limited to organic
hydrogels but has been seen in organogels and inorganic hydrogels. Typically syneresis becomes more pronounced
as the concentration of polymer decreases.
8. Structure: Inorganic particles are capable of gelling a vehicle due to formation of a “house of card” structure. Clays
e.g. bentonite or kaolin posses a lamellar structure that can be extensive hydrated. The flat surface of bentonite
particles are negatively charged while the edges are positively hydrated. The flat surface of bentonite particles are
negatively charged while the edges are positively charged. The attraction of face to edge of these colloidal lamellae
creates a three-dimension network of particles throughout the liquid, immobilizing the solvent. The interactions
between the particles are fairly weak, being broken by stirring or shaking.
9. Rheology: Solutions of gelling agents and dispersions of flocculated solids are typically pseudo plastic, exhibiting
non-Newtonian flow behavior characterized by decreasing viscosity with increasing shear rate. Such behavior is due
to progressive breakdown of the structure of the system.
The tenuous structure of inorganic particles dispersed in water is disrupted by an applied shear stress. As shear stress
is increased, more and more interparticulate associations are broken, resulting in a greater tendency to flow.
Similarly, for macromolecules dispersed in a solvent, the applied shear tends to align the molecules in the direction
of flow. The molecules straighten out, becoming less entangled as shear increases, thus lessening the resistance to
flow.
CLASSIFICATION:
Based on colloidal phases: Gels are classified into inorganic (two phase system) and organic (single phase) gels on
the basis of their nature of colloidal phase present. In a two phase system, if the particle size of the dispersed phase is
relatively large and forms the three dimensional “house of cards” structures throughout the gel, then the gel mass
sometime is referred to as magma (eg.bentonite magma). A gel with two phase system generally consists of floccules
of small particles rather than large molecules and gel structure in such a system is not always stable. Both gels and
magma may be thixotropic forming semisolids on standing and becomes liquid an agitation.

A single phase gel consists of large organic molecules existing on twisted matted strands, dissolved in a
continuous phase, such that no apparent boundaries exist between the dispersed macromolecules and the liquid. this
large organic molecule either natural or synthetic polymers often referred as gel formers, tends to entangle with each
other due to their random motion or bounded together by stronger types of vander-waals force so as to form
crystalline or amorphous regions throughout the entire system.
Single phase in macro sense considers the molecule to be dissolved in continuous solvent phase; however the
unique behaviors of long macromolecules in solutions, leading to fairly high viscosities and gel formation makes it
possible to consider such a system as two phase, at micro level- the dispersion of lyophillic colloidal polymer
molecule and the continuous phase solvent. Single phase gels may be made from synthetic macromolecules (E.g.
carbomer), semi-synthetic natural polymer (E.g. Cellulose derivatives) or natural gums (tragacanth). The later
preparations are also called aqueous, alcohol and oils may be used as the continuous phase. For ex. Mineral oil can be
combined with a polyethylene resin to form an oleaginous ointment base.
Based on nature of solvent: Gels may be classified even as hydrogels (water based) or organo gels (with a
nonaqueous solvent) based on the type of solvent used as continuous liquid phase. Bentonite magma, gelatin,
cellulose derivative, carbomer, polaxomer gels are example of hydrogel. Examples of hydrogels are plastibase (low
molecular weight polyethylene dissolved in mineral oil and stock cooled), olag (aerosil) gel and dispersion of
metallic stearates in oils.
Organogels: Organogels contain a nonaqueous solvent as the continuous phase. Example of organogel are
plastibase(low molecular weight polyethylene dissolved in mineral oil and stock cooled) and dispersions of metallic
stearates in oils. An organogel is a non-crystalline, non-glassy thermo reversible (thermoplastic) solid material
composed of a liquid organic phase entrapped in a three-dimensionally cross-linked network. The liquid can be e.g.
an organic solvent, a mineral oil or a vegetable oil. The solubility and particle dimensions of the structurant are
important characteristics for the elastic properties and firmness of the organogel. Often, these systems are based on
self-assembly of the structurant molecules. Organogels have potential for use in a number of applications, such as in
pharmaceuticals, cosmetics, art conservation, and food. An example of formation of an undesired thermo reversible
network is the occurrence of wax crystallization in crude oil.
Sorbitan monostearate, a hydrophobic nonionic surfactant, gels a number of organic solvents such as
hexadecane, isopropyl myristate, and a range of vegetable oils. Gelation is achieved by dissolving/dispersing the
organogelator in hot solvent to produce an organic solution/dispersion, which, on cooling sets to the gel state.
Cooling the solution/dispersion causes a decrease in the solvent-gelator affinities, such that at the gelation
temperature, the surfactant molecules self-assemble into inverse toroidal vesicles. Further cooling results in the
conversion of the toroids into rod-shaped tubules. Once formed, the tubules associate with others, and a three-
dimensional network is formed which immobilizes the solvent. An organogel is thus formed. Sorbitan monostearate
gels are opaque, thermoreversible semisolids, and they are stable at room temperature for weeks. Such organogels are
affected by the presence of additives such as the hydrophilic surfactant, polysorbate 20, which improves gel stability
and alters the gel microstructure from a network of individual tubules to star-shaped "clusters" of tubules in the liquid
continuous phase.
Another solid monoester in the sorbitan ester family, sorbitan monopalmitate, also gels organic solvents to
give opaque, thermoreversible semisolids. Like sorbitan monostearate gels, the microstructure of the palmitate gels
comprises an interconnected network of rod like tubules. Unlike the stearate gels, however, the addition of small
amounts of a polysorbate monoester causes a large increase in tubular length instead of the clustering effect seen in
stearate gels. The sorbitan stearate and palmitate organogels may have potential applications as delivery vehicles for
drugs and antigens.
Xerogels: solid gels with low solvent concentration are known as xerogels. Xerogels are often produced by
evaporation of the solvent, leaving the gel framework behind. They can be returned to the gel state by introduction of
an agent that,on imbition, swells the gel matrix. Example of xerogels include dry gelatin,tragacanth ribbons and
acacia tears and dry cellulose and polystyrene.
A xerogel is a solid formed from a gel by drying with unhindered shrinkage. Xerogels usually retain high
porosity (25%) and enormous surface area (150–900 m2
/g), along with very small pore size (1-10 nm). When solvent
removal occurs under hypercritical (supercritical) conditions, the network does not shrink and a highly porous, low-
density material known as an aerogel is produced. Heat treatment of a xerogel at elevated temperature produces
viscous sintering (shrinkage of the xerogel due to a small amount of viscous flow) and effectively transforms the
porous gel into a dense glass.

Hydrogel: Hydrogel (also called Aquagel) is a network of polymer chains that are water-insoluble, sometimes found
as a colloidal gel in which water is the dispersion medium. Hydrogels are superabsorbent (they can contain over 99%
water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due
to their significant water content.
Common uses for hydrogels include
 Currently used as scaffolds in tissue engineering. When used as scaffolds, hydrogels may contain human
cells in order to repair tissue.
 Environmentally sensitive hydrogels. These hydrogels have the ability to sense changes of pH, temperature,
or the concentration of metabolite and release their load as result of such a change.
 As sustained-release delivery systems
 Provide absorption, desloughing and debriding capacities of necrotics and fibrotic tissue.
 Hydrogels that are responsive to specific molecules, such as glucose or antigens can be used as biosensors as
well as in DDS.
 Used in disposable diapers where they "capture" urine, or in sanitary napkins
 Contact Lenses (silicone hydrogels, polyacrylamides)
 Medical Electrodes using hydrogels composed of cross linked polymers (polyethylene oxide, polyAMPS and
polyvinylpyrrolidone)
 Water gel explosives
 Other, less common uses include
 breast implants
 granules for holding soil moisture in arid areas
 Dressings for healing of burn or other hard-to-heal wounds. Wound gels are excellent for helping to create or
maintain a moist environment.
 Reservoirs in topical drug delivery; particularly ionic drugs, delivered by iontophoresis (see ion exchange
resin)
 Common ingredients are e.g. polyvinyl alcohol, sodium polyacrylate, acrylate polymers and copolymers with
an abundance of hydrophilic groups.
 Natural hydrogel materials are being investigated for tissue engineering, these materials include agarose,
methylcellulose, hylaronan, and other naturally derived polymers.
Based on Rheological properties: Gels are considers to exhibit non-Newtonian properties. Gels may be classified
based a rheological properties as plastic, pseudo plastic and thixotropic gels. Plastic gels for example Bingham
bodies, flocculated suspension of Al (OH) 2 exhibit a plastic floe and the plot of rheogram gives yield value of gels
above which the elastic gels distorts and begin to flow. Pseudo plastic gels e.g. liquid dispersion of natural gums like
tragacanth, sodium alginate, methyl cellulose, sodium CMC, exhibit pseudo plastic flow. The viscosity of pseudo
plastic gels decreases with increasing rate of shear, with no yield value. The rheogram for pseudo plastic material
results from a shearing action on the long chain molecules of the linear polymers. As the shearing stress is increased,
the disarranged molecules begin to align their long axis in the direction of flow with release of solvent from gel
matrix.
Thixotropic gels: The bonds between particles in these gels are very weak and can be broken down by a shaking or
stirring. The resultant sol will revert back to gel due to the particle colliding and linking together again the reversible
isothermal sol gel transformation is termed thixotropy. It is most likely to occur in colloidal system with non-
spherical particles, to build up a scaffold like structure eg. Bentonite, kaolin and agar 0.5%.
Based on the physical nature: Based on the physical nature i.e. consistency of gel they are classified as elastic and
rigid gels.
Elastic gel: Gel of agar, pectin, gaur gum, gelatin, and alginate exhibit a elastic behavior. The fibrous molecules
being linked at the point of junction by relatively posses weak bounds such as hydrogen bounds and dipole attraction.
If the molecule posses free –COOH group then additional bounding takes by salt bridge of type –COO-X2 +
-COO
between two adjacent strands network (ex. Alginate and carbopols) where “X” is linking atom/molecule. The type of
link imparts elastic behavior to the gel and builds coulombs force, hydrogen bounding, and vander-waals force of
attraction between gelling polymers.
Rigid gels: It can be formed from macromolecule in which the framework linked by primary valence bound e.g. in
solid silica gel, silicic acid molecules are held by Si-O-Si-O bound to give a polymer structure possessing a network

of pores. The rigid gels are even formed in case of polaxomers by thermal changes or reaction between poly vinyl
alcohols with glycidyl ether or toluene disocyanate or methane diphenyl isocynate.
GEL FORMING SUBSTANCES:
A number of polymers are used to provide the structural network that is the essence of a gel system. These include
natural gums, cellulose derivatives, and carbomers. Although most of these function in aqueous media, several
polymers that can gel nonpolar liquids are also available. Certain colloidal solids behave as gallants as a result of
asymmetric flocculation of the particles. High concentration of some nonionic surfactants can be used to produce
clear gel in systems containing up to about 15% mineral oil. These are employed mostly as hair dressings.
Gel forming polymers are classified as follows:
A. Natural polymer
1. Agar
2. Alginates
3. carageenan
4. Tragacanth
5. Pectin
6. Xanthan
7. Gellan Gum
8. Guar Gum
9. Other gums
10. Chitosan etc.
B. Semi synthetic polymers
1. Cellulose derivatives
2. Carboxymethyl cellulose
3. Methylcellulose
4. Hydroxypropyl cellulose
5. Hydroxy propyl (methyl cellulose)
6. Hydroxyethyl cellulose etc.
C. Synthetic polymers
1. Carbomer
2. Carbopol 934
3. Carbopol 940
4. Carbopol 980 etc.
5. Poloxamer/surfactants
6. Polyacrylamide
7. Polyethylene and its co-polymers
D. Inorganic substances
1. Microcrystalline silica
2. Clays
E. Other gallants
1. Beeswax
2. Cetyl ester wax
3. Aluminum staerate etc.
A. Natural polymers: Natural gums have been used in commerce since the beginning of recorded history. Typically,
they are branched-chain polysaccharides. Most are anionic (negative charged in aqueous solution or dispersion),
although a few, such as gaur, are neutral molecules. Differences in proportion of the sugar building blocks that make
up these molecules and their arrangement and molecular weight result in significant variations in gum properties.
Because of their chemical makeup, neutral gums are subjected to microbial degradation and support microbial
growth. Aqueous systems containing gums should contain a suitable preservative. As mentioned earlier, cationic
antimicrobials are not generally compatible with the anionic gums and should usually be avoided. Although many of
the most familiar gums are plant exudates of extracts, other sources are also used.
1. Alginates: These polysaccharides containing varying proportion of D-mannuronic and L-guluronic acids are
derived from brown seaweed in the form of monovalent and divalent salts. Although other alginate salts are available
commercially, sodium alginate is by far the most widely used. Gelation occurs by reduction of pH or reaction with

divalent cations. Reduction of pH converts the carboxylate ions to free carboxyl groups. This reduces hydration of
polymer segments as well as the repulsion between them. Generally, some calcium must be present; the small
amounts contributed by the alginate may be sufficient. The pH at which gelation occurs calcium begins to gel below
a pH 4. Gel strength is a function of alginate concentration; 0.5% is a practical minimum.
2. Carrageenan: All the carrageenans are anionic. Carrageenan, the hydrocolloid extracted from red seaweed, is a
variable mixture of sodium, potassium, ammonium, calcium and magnesium sulfate esters of polymerized galactose,
and 3,6-anhydrogalactose. The main copolymer types are labeled kappa-, iota-, and lambda-carrageenan. Kappa and
iota fraction form thermally reversible gels in water. This has been ascribed to a temperature-sensitive molecular
rearrangement. At high temperature, the copolymers exist as random coils; cooling result in formation of double
helices that act as cross-links.
3. Tragacanth: Trgacanth is defined in the NFas the “dried gummy exudation from Astragalus gummifer
Labillardiere, or other Asiatic species of Astragalus. Tragacanth is a complex material composed of chiefly of acidic
polysaccharide (tragacanth acid) containing calcium, magnesium, and potassium, and a smaller amount of a neutral
polysaccharide, tragacanthin. The gum swells in water; concentrations of 2 % or above a “high-quality” gum produce
a gel.
4. Pectin: Pectin, the polysaccharide extracted from the inner skin of citrus fruit or apple pomance, may be used in
pharmaceutical jellies as well as in foods. The gel is formed at an acid pH in aqueous solutions containing calcium
and possibly another agent that acts to dehydrate the gum.
5. Xanthan gum: Although xanthan gum is used most frequently as a stabilizer in suspensions and emulsions at
concentrations below 0.5%, higher concentrations in aqueous media yield viscid solutions that are jellylike in nature.
Xanthan gum is produced by bacterial fermentation, and other its availability and quality are not subject to many of
the uncertainties that affect other natural products, particularly those that are extracted from plants whose habitat falls
within politically unsettled part of the world. Thermally reversible gels result from combinations of xanthan with
gaur or locust bean gum.
6. Gellan gum: Gellan gum is another polysaccharide produced by fermentation that has FDA clearance for use in
foods. The gum is highly efficient; as little as 0.05% is required for gel formation. Gels will not form in the absence
of free cations. While both monovalent and divalent ions can include gelation, the divalent ions are required in much
lower concentration, roughly 1/25 the concentration of monovalent ions. To produce a uniform gel, the gum is first
dissolved in deionized water heated to 70-75°C.
7. Guar gum: Guar gum is a nonionic polysaccharide derived from seeds. Aqueous guar solutions can be cross-
linked by several polyvalent cations to form gels. The mechanism is believed to involve chelate formation between
groups in different polymer chains. A disadvantage of these gels is the presence of insoluble plant residue.
8. Other gums: Gelatin is used widely as a bodying agent and gel former in the food industry, and occasionally in
pharmaceutical products. Agar can be used to make firm gels, it is most frequently used in culture media.
9. Chitosan: Chitosan is a natural biopolymer derived from the outer shell of crustaceans. Chitin is extracted and
partially deacetylated to produce chitosan. Unlike most gums, chitosan carries a positive charge and is thus attracted
to a variety of biological tissues and surfaces that are negatively charged. Various derivatives are being explored for
specific applications. Concentrated aqueous solutions have a gel-like consistency. Firmer gels result from interaction
with polysaccharides, such as alginate.
B. Semi synthetic polymers
Cellulose derivatives: Many useful derivatives are fashioned from cellulose, a natural structure polymer found in
plants. Treatment in the presence of various active substances results in breakdown of the cellulose backbone as well
as substitution of a portion of its hydroxyl moieties. The major factors affecting rheological properties of the resultant
material are the nature of the substitution(s), degree of substitution, and average molecular weight of the resultant
polymer.
Carboxymethylacellulose: Carboxymethylcellulose, also known as sodium carboxymethylcellulose, CMC, and
cellulose gum, is an anionic polymer available in a variety of grades that differ in molecular weight and degree of
substitution. Gelation requires addition of an electrolyte with a polyvalent cation to a solution of the polymer;
aluminum salts are proffered.
Methylcellulose: Methylcellulose is an example of a polymer whose solubility in water decreases as the temperature
is raised. If an aqueous solution is heated, viscosity increases markedly at a certain point as the result of aqueous
solution is heated, viscosity increases markedly at a certain point as the result of formation of gel structure. This
property, known as thermal gelation, is a function of polymer chemistry and the presence of additives. The gelation

temperature range for methocel type A is 50-55 °C. Salts and sugars with a high affinity for water lower the gelation
temperature whereas alcohol and propylene glycol have the opposite effect.
Other cellulose derivatives: Hydroxypropyl cellulose is soluble in water as well as many polar organic solvents.
Consequently, it is useful as a gelling agent for such liquids and for mixture of water and various organic liquids,
such as alcohol, that adversely affect the rheological properties of gums and certain other hydrophilic agents. High
molecular weight grades of hydroxypropyl cellulose and hydroxyethyl cellulose, though highly viscous, behave as
fluids and do not exhibit a yield value.
C. Synthetic polymers
Carbomer: Carbopol® polymers, along with Pemulen® polymeric emulsifiers are all cross-linked. They swell in
water up to 1000 times their original volume (and ten times their original diameter) to form a gel when exposed to a
pH environment between 4.0 - 6.0. Since the pKa of these polymers is 6.0 ± 0.5, the carboxylate groups on the
polymer backbone ionize, resulting in repulsion between the negative charges, which adds to the swelling of the
polymer. Cross-linked polymers do not dissolve in water. The glass transition temperature of Carbopol® polymer is
105°C in powder form. However, the glass transition temperature drops dramatically as the polymer comes into
contact with water. The polymer chains starts gyrating and the radius of gyration becomes larger. Macroscopically,
this phenomenon manifests itself as swelling. Carbopol® polymers and co-polymers are used mainly in liquid or
semisolid pharmaceutical formulations as suspending or viscosity increasing agents. Formulations include creams,
gels and ointments. Carbopol® polymers are also employed as emulsifying agents in the preparation of o/w
emulsions for external use and are also employed in cosmetics (C. Rowe, 2003).
Poloxamer/surfactants: Poloxamer is a synthetic block copolymer of ethylene oxide and propylene oxide. Their
molecular weight ranges from 1000-15000. In a molecule the hydrophilic poly (oxyethylene) sand witches the
hydrophilic poly (oxypropylene) thereby the polo oxypropylene occupies a central position in the molecule and it is
flanked by two hydrophilic polyoxyethylene blocks. The differences in the chain length of the polyoxyethylene and
polyoxypropylene chains in different products are responsible for the divergences in their physical, chemical and
practical properties.
Polyethylene and its co-polymers: Various forms of polyethylene and its copolymers are used to gel hydrophobic
liquids. The result is a soft, easily spreadable semisolid that forms a water-resistant film on the skin surface.
Polyethylene itself is a suitable gellant for simple aliphatic hydrocarbon liquids but may lack compatibility with
many other oils found in personal care products. For, these, copolymers with vinyl acetate and acrylic acid may be
used, perhaps with the aid of a co-solvent. To form the gels, it is necessary to disperse the polymer in the oil at
elevated temperature (above 80 °C) and then shock cool to precipitate fine crystals that make up the matrix.
D. Inorganic Substances: Certain finely divided solids can function efficiently as thickening agents in various liquid
media. Gel formation depends on establishment of a network in which colloidal particles of the solid are connected in
an asymmetric fashion. This requires mutual attraction of the particles (flocculation) and partial wetting by the liquid.
Microcrystalline silica: Microcrystalline silica can functions as a gallant in a wide range of liquids. Network
formation results from attraction of the particles by polar forces, principally hydrogen bonding.
An important commercial application of silica is its use in dentifrices. Microcrystalline silica acts as a bonding agent
that provides thixotropy to the formation; at the same time, the required concentration of polishing agents is required.
Clays: Montmorillonite clays are capable of swelling in water as the result of hydration of exchangeable cations and
electrostatic repulsion between the negatively charged faces. At high concentration in water, thixotropic gels are
fromed because the particles combine in a flocculated structure in which the face of one particle is attracted to the
edge of another.
METHOD OF PREPARATION OF GELS
Gels are normally in the industrial scale prepared under room temperature. However few of the polymers need
special treatment before processing. The gel preparation can be categorized under the following headings:
Gel prepared by thermal change: The solubility of most lyophilic colloids e.g. Gelatin, agar is reduced on lowering
the temperature, so that cooling a concentrated hot sol will often produce a gel. In contrast to this, some material such
as the cellulose ethers owe their water solubility to hydrogen bonding with the water. Raising the temperature of
these sols will disrupt the hydrogen bonding and the reduced solubility will cause gelation.
Gel prepared by flocculation with neutralizers: Gelation is produced by adding just sufficient precipitation to
produce the gel state but insufficient to bring about complete precipitation. It is necessary to ensure rapid mixing to
avoid local high concentrations of precipitant. Solutions of ethyl cellulose, polystyrene in benzene can be gelled by
rapid mixing with suitable amounts of a nonsolvent such as petroleum ether. The additions of salts to hydropholic

sols bring coagulation, and gelation is rarely observed. The additions of suitable proportion of salts to moderately
hydrophilic sols such as aluminum hydroxide, bentonite, etc. produce gels. The gels formed are frequently
thixotropic in behavior. Hydrophilic colloids such as gelatin and acacia are only affected by high concentration of
electrolytes, when the effect is to “salt out” the colloid and gelation does not occur.
Gel prepared by chemical reaction: In the preparation of sols by precipitation from solution e.g. aluminum
hydroxide sol prepared by interaction in aqueous solution of an aluminum salt and sodium carbonate, an increased
concentration of reactants will produce a gel structure.
USES
The uses of gels and gelling are quite widespread, but discussion here is limited to the pharmaceutical and
cosmetic fields only. Gels find use as delivery system for oral administration as gels proper or as capsule shells made
from gelatin; for topical drug applied directly to the skin,mucous membranes, or eye ; and for long-acting forms of
drug injected intramuscularly or implanted into the body. Geliing agents are useful as binders in tablet
granulations,protective colloids in suspensions, thickeners in oral liquids, and suppository bases. Cosmetically, gels
have been employed in a wide variety of products,including shampoos,fragrance products,dentifrices, and skin and
hair-care preparation.
CONLUSION
Dermatological formulations are among the most frequently compounded products because of their wide
range of potential uses. These include solutions (i.e., collodions, liniments, aqueous and oleaginous solutions),
suspensions and gels, emulsions, lotions, and creams. Lotions can be either suspensions or emulsions but are fluid
liquids that are typically used for their lubricating effect. Creams are emulsions and are typically opaque, thick
liquids or soft solids used for their emollient properties. Creams also have the added feature that they tend to "vanish"
or disappear with rubbing.
REFERENCES
Alfred Martin, James Swarbrick, Arthur Cammarala, Physical Pharmacy 3rd Edition, 1983, 56-569, 522, 542.
C. Rowe, P. J. Sheskey, P. J. Weller, Handbook of Pharmaceutical Excipients 4th Edition, Pharmaceutical Press,
London, UK, 2003, 89 - 92.
Fresno,M. J. C. Ramírez A. D., Jiménez M. M..Systematic study of the flow behaviour and mechanical properties
of Carbopol hydroalcoholic gels. European Journal of Pharmaceutics and Biopharmaceutics, 2002, 54, 329 - 335.
Herbert A Libermen, Martin M Rieger, Gilbert S Banker, Gels: In Pharmaceutical Dosage Forms, Dispersed
Systems, Informa Health Care,1996, 399-419
Herbert A. Libermen,Martin M.Rieger, Gilbert S. Banker, Gels. In Pharmaceutical Dosage Forms, Dispersed
Systems, Informa Health Care, 1996, 399-419.
Herbert A. Libermen,Martin M.Rieger, Gilbert S. Banker. Gels. In Pharmaceutical Dosage Forms, Informa Health
Care, 1996, 399-419.
Lachman HP, Lieberman JL, Kanig, Theory and Practice of Industrial Pharmacy, 3rd Edition, Varghese
Publishing House, Bombay, 1987, 534-548.
MN Nutimer, Chromatograph, Biomed App, 420, 1987, 228-230.

J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
RECENT TRENDS OF POLYMER USAGE IN THE FORMULATION OF
ORODISPERSIBLE TABLETS
J.Preethi, MD Farhana, B.Chelli Babu, MD.Faizulla, Debjit Bhowmik*
, S.Duraivel
Nimra College Pharmacy, Nimranagar, Vijayawada, Andhra Pradesh, India
*Corresponding author: debjit_cr@yahoo.com
ABSTRACT
Disintegrants are an essential component to tablet formulations. While rapidly disintegrating tablets do
not necessarily ensure fast bioavailability, slowly disintegrating tablets almost always assure slow
bioavailability. The ability to interact strongly with water is essential to disintegrant function. Combinations of
swelling and/or wicking and/or deformation are the mechanisms of disintegrant action. Super disintegrants
offer significant improvements over starch. But hygroscopicity may be a problem in some formulations. Tablet
disintegration has received considerable attention as an essential step in obtaining fast drug release.
Disintegration remains a powerful influence and precursor for drug absorption. Disintegration of tablet or
capsule is depending upon the type and quantity of disintegrants. The development of Orodispersible tablets
provides an opportunity to take an account of tablet disintegrants. Therefore, there is a huge potential for the
evaluation of new disintegrants or modification of an existing disintegrants into superdisintegrants, so as to
formulate Orodispersible tablets. The present study comprises the various kinds of disintegrants and
superdisintegrants, which are being used in the formulation to provide the safer, effective drug delivery with
patient's compliance.
Key words: Super disintegrants, Polysorbate, Modified starches, Modified cellulose, Crospovidone
1. INTRODUCTION
Bioavailability of a drug depends in absorption of the drug, which is affected by solubility of the drug in
gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. The drugs solubility mainly
depends on physical – chemical characteristics of the drug. However, the rate of drug dissolution is greatly
influenced by disintegration of the tablet. The drug will dissolve at a slower rate from a non-disintegrating tablet due
to exposure of limited surface area to the fluid. The disintegration test is an official test and hence a batch of tablet
must meet the stated requirements of disintegration. Disintegrants are substances or mixture of substances added the
drug formulation that facilitates the breakup or disintegration of tablet or capsule content into smaller particles that
dissolve more rapidly than in the absence of disintegrants. Superdisintegrants are generally used at a low level in the
solid dosage form, typically 1 to 10 % by weight relative to the total weight of the dosage unit. Examples of
Superdisintegrants are crosscarmelose, crosspovidone, sodium starch glycolate which represent example of a
crosslinked cellulose, crosslinked polymer and a crosslinked starch respectively.
Superdisintegrants -an economical alternative: Orally disintegrating tablets are an emerging trend in formulation,
gaining popularity due to ease of administration and better patient compliance for geriatric and pediatric patients.
Disintegrating agents are substances routinely included in tablet formulations and in some hard shell capsule
formulations to promote moisture penetration and dispersion of the matrix of the dosage form in dissolution fluids.
An oral solid dosage form should ideally disperse into the primary particles from which it was prepared. Although
various compounds have been proposed and evaluated as disintegrants, relatively few are in common usage today.
Traditionally, starch has been the disintegrant of choice in tablet formulations, and it is still widely used. However,
starch is far from ideal. For instance, starch generally has to be present at levels greater than 5% to adversely affect
compactibility, especially in direct compression. Moreover, intragranular starch in wet granulations is not as effective
as dry starch. In more recent years, several newer disintegrants have been developed. Often called “super
disintegrants,” these newer substances can be used at lower levels than starch. Because they can be a smaller part of
the overall formulation than starch, any possible adverse effect on fluidity or compactibility would be minimized.
These newer disintegrants may be organized into three classes based on their chemical structure (Table 1).
Method of addition of disintegrants: The requirement placed on the tablet disintegrant should be clearly defined.
The ideal disintegrant has-
1. Poor solubility
2. Poor gel formation
3. Good hydration capacity
4. Good molding and flow properties
5. No tendency to form complexes with the drugs

Disintegrants are essentially added to tablet granulation for causing the compressed tablet to break or disintegrate
when placed in aqueous environment. There are two methods of incorporating disintegrating agents into the tablet:
I. Internal Addition (Intragranular)
II.External Addition (Extragranular)
III.Partly Internal and External
In external addition method, the disintegrant is added to the sized granulation with mixing prior to
compression. In Internal addition method, the disintegrant is mixed with other powders before wetting the powder
mixtures with the granulating fluid. Thus the disintegrant is incorporated within the granules. When these methods
are used, part of disintegrant can be added internally and part externally. This provides immediate disruption of the
tablet into previously compressed granules while the disintegrating agent within the granules produces further
erosion of the granules to the original powder particles. The two step method usually produces better and more
complete disintegration than the usual method of adding the disintegrant to the granulation surface only.
Table 1 Classification of “super disintegrants” (partial listing)
Structural type (NF name) Description Trade name (manufacturer)
Modified starches (Sodium
starch glycolate, NF)
Sodium carboxymethyl starch; the
carboxymethyl groups induces
hydrophilicity and cross-linking
reduces solubility.
Explotab®(Edward Mendell Co.)
Primojel® (Generichem Corp.) Tablo®
(Blanver, Brazil)
Modified cellulose
(Croscarmellose, NF)
Sodium carboxymethyl cellulose
which has been cross-linked to render
the material insoluble.
AcDiSol® (FMC Corp.) Nymcel ZSX®
(Nyma, Netherlands) Primellose®
(Avebe, Netherlands) Solutab®
(Blanver, Brazil)
Cross-linked poly-
vinylpyrrolidone
(Crospovidone, NF)
Cross-linked polyvinylpyrrolidone;
the high molecular weight and cross-
linking render the material insoluble
in water.
Crospovidone M® (BASF Corp.)
Kollidon CL® (BASF Corp.)
Polyplasdone XL (ISP Corp.)
Factors affecting action of disintegrants:
1. Percentage of disintegrants present in the tablets.
2. Types of substances present in the tablets.
3. Combination of disintegrants.
4. Presence of surfactants.
5. Hardness of the tablets.
6. Nature of Drug substances.
7. Mixing and Screening.
Effect of fillers:The solubility and compression characteristics of fillers affect both rate and mechanism of
disintegration of tablet. If soluble fillers are used then it may cause increase in viscosity of the penetrating fluid
which tends to reduce effectiveness of strongly swelling disintegrating agents and as they are water soluble, they are
likely to dissolve rather than disintegrate. Insoluble diluents produce rapid disintegration with adequate amount of
disintegrants. Chebli and cartilier proved that tablets made with spray dried lactose (water soluble filler) disintegrate
more slowly due to its amorphous character and has no solid planes on which the disintegrating forces can be exerted
than the tablet made with crystalline lactose monohydrate.
Effect of binder: As binding capacity of the binder increases, disintegrating time of tablet increases and this
counteract the rapid disintegration. Even the concentration of the binder can also affect the disintegration time of
tablet.
Effect of lubricants: Mostly lubricants are hydrophobic and they are usually used in smaller size than any other
ingredient in the tablet formulation. When the mixture is mixed, lubricant particles may adhere to the surface of the
other particles. This hydrophobic coating inhibits the wetting and consequently tablet disintegration. Lubricant has a
strong negative effect on the water uptake if tablet contains no disintegrants or even high concentration of slightly
swelling disintegrants. On the contrary, the disintegration time is hardly affected if there is some strongly swelling
disintegrants are present in the tablet. But there is one exception like sodium starch glycolate whose effect remains
unaffected in the presence of hydrophobic lubricant unlike other disintegrants.

Effect of surfactants: Sodium lauryl sulphate increases absorption of water by starch. Surfactants are only effective
within certain concentration ranges. Surfactants are recommended to decrease the hydrophobicity of the drugs
because the more hydrophobic the tablet the greater the disintegration time.
Table.2. Effects of various surfactants on the disintegration of tablets containing various drugs
SURFACTANT REMARKS
Sodium lauryl sulfate Good-various drugs Poor - various drugs
Polysorbate 20 Good
Polysorbate 40 & 60 Poor
Polysorbate 80 Good
Tweens Poor
Poly ethylene glycol Poor
(Good – decrease in disintegration time, Poor – increase in disintegration time)
Superdisintegrants used in formulation of orodispersible tablets: Disintegrating agents are substances routinely
included in the tablet formulations to aid in the breakup of the compacted mass when it is put into a fluid
environment. They promote moisture penetration and dispersion of the tablet matrix. In recent years, several newer
agents have been developed known as “Superdisintegrants”. These newer substances are more effective at lower
concentrations with greater disintegrating efficiency and mechanical strength. On contact with water the
superdisintegrants swell, hydrate, change volume or form and produce a disruptive change in the tablet. Effective
superdisintegrants provide improved compressibility, compatibility and have no negative impact on the mechanical
strength of formulations containing high-dose drugs. The commonly available superdisintegrants along with their
commercial trade names are briefly described herewith.
Modified starches: Sodium starch glycolate is the sodium salt of a carboxymethyl ether of starch. It is effective at a
concentration of 2-8%. It can take up more than 20 times its weight in water and the resulting high swelling capacity
combined with rapid uptake of water accounts for its high disintegration rate and efficiency. It is available in various
grades i.e. Type A, B and C, which differ in pH, viscosity and sodium content. Other special grades are available
which are prepared with different solvents and thus the product has a low moisture (<2%) and solvent content (<1%),
thereby being useful for improving the stability of certain drugs.
Modified celluloses Carboxymethylcellulose and its derivative (Croscarmellose Sodium): Cross-linked sodium
carboxymethylcellulose is a white, free flowing powder with high absorption capacity. It has a high swelling capacity
and thus provides rapid disintegration and drug dissolution at lower levels. It also has an outstanding water wicking
capability and its cross-linked chemical structure creates an insoluble hydrophilic, highly absorbent material resulting
in excellent swelling properties. Its recommended concentration is 0.5–2.0%, which can be used up to 5.0% L-HPC
(Low substituted Hydroxy propyl cellulose) It is insoluble in water, swells rapidly and is used in the range of 1-5%.
The grades LH- 11 and LH-21 exhibit the greatest degree of swelling.
Cross-linked polyvinylpyrrolidone: It is a completely water insoluble polymer. It rapidly disperses and swells in
water but does not gel even after prolonged exposure. The rate of swelling is highest among all the superdisintegrants
and is effective at 1-3%. It acts by wicking, swelling and possibly some deformation recovery. The polymer has a
small particle size distribution that imparts a smooth mouth feel to dissolve quickly. Varieties of grades are available
commercially as per their particle size in order to achieve a uniform dispersion for direct compression with the
formulation.
Soy polysaccharide: It is a natural super disintegrant that does not contain any starch or sugar so can be used in
nutritional products.
Cross-linked alginic acid: It is insoluble in water and disintegrates by swelling or wicking action. It is a hydrophilic
colloidal substance, which has high sorption capacity. It is also available as salts of sodium and potassium.
Gellan gum: It is an anionic polysaccharide of linear tetrasaccharides, derived from Pseudomonas elodea having
good superdisintegrant property similar to the modified starch and celluloses.
Xanthan gum: Xanthan Gum derived form Xanthomonas campestris is official in USP with high hydrophilicity and
low gelling tendency. It has low water solubility and extensive swelling properties for faster disintegration.
Calcium Silicate: It is a highly porous, lightweight superdisintegrant, which acts by wicking action. Its optimum
concentration range is 20-40%

Ion exchange resins: The INDION 414 has been used as a superdisintegrant for ODT. It is chemically cross-linked
polyacrylic, with a functional group of – COO – and the standard ionic form is K+. It has a high water uptake
capacity.
Others: Although there are many superdisintegrants, which show superior disintegration, the search for newer
disintegrants is ongoing and researchers are experimenting with modified natural products, like formalincasein,
chitin, chitosan, polymerized agar acrylamide, xylan, smecta, key-jo-clay, crosslinked carboxymethylguar and
modified tapioca starch.
Mechanism of action of superdisintegrating agent: Disintegrants are agents added to tablet (and some
encapsulated) formulations to promote the breakup of the tablet (and capsule “slugs’) into smaller fragments in an
aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug
substance. There are three major mechanisms and factors affecting tablet disintegration as follows:
A: Swelling: Although not all effective disintegrants swell in contact with water, swelling is believed to be a
mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in
contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart.
B: Porosity and Capillary Action (Wicking): Effective disintegrants that do not swell are believed to impart their
disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of
fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance
porosity and provide these pathways into the tablet. Liquid is drawn up or “wicked” into these pathways through
capillary action and rupture the interparticulate bonds causing the tablet to break apart.
C: Deformation: Starch grains are generally thought to be “elastic” in nature meaning that grains that are
deformed under pressure will return to their original shape when that pressure is removed. But, with the compression
forces involved in tableting, these grains are believed to be deformed more permanently and are said to be “energy
rich” with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher
in “energy rich” starch grains than it is for starch grains that have not been deformed under pressure. It is believed
that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of
inter-relationships between these major mechanisms.
The classical example of the earliest known disintegrant is Starch. Corn Starch or Potato Starch was
recognized as being the ingredient in tablet formulations responsible for disintegration as early as 1906 (even though
tablet disintegration was itself not given much importance in tablet formulations until much later).
Until fairly recently, starch was the only excipient used as a disintegrant. To be effective, corn starch has to
be used in concentrations of between 5-10%. Below 5%, there is insufficient “channels” available for wicking (and
subsequent swelling) to take place. Above 10%, the incompressibility of starch makes it difficult to compress tablets
of sufficient hardness.
Although the connection between bioavailability of drug and tablet disintegration took some time to become
appreciated, it is now accepted that the role of the disintegrant is extremely important. In a direct compression
process, drug is blended with a variety of excipients, subsequently lubricated and directly compressed into a tablet. A
disintegrant used in this type of formulation, simply has to break the tablet apart to expose the drug substance for
dissolution.
Pregelatinized Starch (Starch 1500): Pregelatinized starch is a directly compressible form of starch consisting of
intact and partially hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a
binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 5-10%. It’s major
mechanism of action as a disintegrant is thought to be through swelling.
Microcrystalline Cellulose (Avicel): Like pregelatinized starch, microcrystalline cellulose is widely used in
formulations because of its excellent flow and binding properties. It is also an effective tablet disintegrant when used
in a concentration of between 10-20%.
Others: Sodium Bicarbonate in combination with citric or tartaric acids is used as an “effervescent”
disintegrant.Alginic Acid at a concentration of between 5-10% is an effective, but very expensive disintegrant.Ion
Exchange Resins (Amberlite 88) has disintegrant properties at a concentration of between 1-5%. But this type of
disintegrant is rarely used.
Super disintegrants: Because of the increased demands for faster dissolution requirements, there are now available,
a new generation of “Super Disintegrants” in addition to the disintegrants discussed earlier.
Three major groups of compounds have been developed which swell to many times their original size when placed in
water while producing minimal viscosity effects:

1. Modified Starches: Sodium Carboxymethyl Starch (Chemically treated Potato Starch) i.e. Sodium Starch
Glycolate (Explotab, Primogel)
Mechanism of Action: Rapid and extensive swelling with minimal gelling.
Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to gelling and its
subsequent viscosity producing effects.
2. Cross-linked polyvinylpyrrolidone: water insoluble and strongly hydrophilic. i.e. crospovidone (Polyplasdone
XL, Kollidon CL) Mechanism of Action: Water wicking, swelling and possibly some deformation recovery.
Effective concentration: 2-4%
dified Cellulose: Internally cross-linked form of Sodium carboxymethyl cellulose. i.e. Ac-Di-Sol (Accelerates
Dissolution), Nymcel
Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling.
Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation)
ADVANTAGES:
 Effective in lower concentrations than starch
 Less effect on compressibility and flow ability
 More effective intragranularly
DISADVANTAGES:
 More hygroscopic (may be a problem with moisture sensitive drugs)
 Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo).
Table.3. List of disintegrants
Disintegrants Concentration in granules (%w/w) Special comments
Starch USP 5-20 Higher amount is required, poorly
compressible
Starch 1500 5-15 -
Avicel®
(PH 101, PH
102)
10-20 Lubricant properties and directly
compressible
Solka floc®
5-15 Purified wood cellulose
Alginic acid 1-5 Acts by swelling
Na alginate 2.5-10 Acts by swelling
Explotab®
2-8 Sodium starch glycolate,
superdisintegrant.
Polyplasdone®
(XL) 0.5-5 Crosslinked PVP
Amberlite®
(IPR 88) 0.5-5 Ion exchange resin
Methyl cellulose, Na
CMC, HPMC
5-10 -
AC-Di-Sol®
1-3 Direct compression
2-4 Wet granulation
CONCLUSION:
Disintegrants, an important excipient of the tablet formulation, are always added to tablet to induce breakup
of tablet when it comes in contact with aqueous fluid and this process of desegregation of constituent particles before
the drug dissolution occurs, is known as disintegration process and excipients which induce this process are known as
disintegrants.The objectives behind addition of disintegrants are to increase surface area of the tablet fragments and
to overcome cohesive forces that keep particles together in a tablet. One of the challenges every formulator of oral
solid dosage forms must address is drug solubility. Drugs must dissolve efficiently to be absorbed by the body, but
this is a special challenge fo rpoorly soluble drugs. The choice of formulation ingredients can have a significant
effect on the rate and extent of drug dissolution. Superdisintegrants used as enhance solubililty of poorly water
soluble drugs.

Table.4. List of superdisintegrants
SUPERDISINTEGRANTS EXAMPLE
OF
MECHANISM OF
ACTION
SPECIAL COMMENT
Crosscarmellose®
, Ac-Di-Sol®
,
Nymce ZSX®
, Primellose®
,
Solutab®
, Vivasol®
Crosslinked
cellulose
Swells 4-8 folds in < 10
seconds.
Swelling and wicking
both.
Swells in two dimensions,
Direct compression or
granulation, Starch free
Crosspovidone, Crosspovidon
M®
, Kollidon®
, Polyplasdone®
Crosslinked
PVP
Swells very little and
returns to original size
after ompression but act
by capillary action
Water insoluble and spongy in
nature so get porous tablet
Sodium starch glycolate
Explotab®
, Primogel®
Crosslinked
starch
Swells 7-12 folds in <30
seconds
Swells in three dimensions and
high level serve as sustain
release matrix
Alginic acid NF Satialgine®
Crosslinked
alginic acid
Rapid swelling in
aqueous medium or
wicking action
Promote disintegration in both
dry or wet granulation
Soy polysaccharides
Emcosoy®
Natural super
disintegrant
Does not contain any starch or
sugar. Used in nutritional
products.
Calcium silicate Wicking action Highly porous, light weight
optimum concentration is
between 20-40%
REFERENCES
Bi Y, Sunada H, Yonezawa Y, Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral
cavity, Chem Pharm Bull (Tokyo), 44, 1996, 2121-2127.
Bi YX, Sunada H, Yonezawa Y, Danjo K.Evaluation of rapidly disintegrating tablets prepared by a direct
compression method, Drug Dev Ind Pharm, 25, 1999, 571-581.
Chaudhari K.P.R, and Rao Rama N, Indian Drugs, 35 (6), 1988, 368 to 371,
Chudhari K. P.R, and Radhika, Int. J. Pharm. Excipts, 2000 (4), 181-184
Grasono Alesandro et al, US Patent 6, 1997, 336 2001
Grasono, Alessandro et al, U S Patent 6,197,336 2001
Ihang J. A., & Christensen J. M., Drug Dev Ind Pharn, 22 (8), 1996, 833-839
Korunubhum S. S., Batopak S. B., J. Pharm Sci, 62 (1), 1973, 43-49
Liberman H.A., Lachman L. and Schawstr J.B., Pharmaceutical Dosage forms, tablets, vol 2, 1989, 173-177
Sallam E, Ibrahim H, Abu Dahab R, Shubair M, Khalil E.Evaluation of fast disintegrants in terfenadine tablets
containing a gas-evolving disintegrant, Drug Dev Ind Pharm, 24, 1998,501-507.
Sallem E, Ibrahim H, Dahab R. A, Drug Dev. Ind. Pharm, 24 (6), 1998, 501-507
Schimidt P.C and Brogramann B, Acta. Pharm. Technol, 1988, 34, 22.

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