B.PHARMACY PROJECT WORK

1. FORMULATION AND EVALUATION
OF ORAL FAST DISSOLVING FILMS
OF RISPERIDONE
Presented By
G.NIKITHA-13Y21R0015
KALYANI-13Y21R0011
RANI-13Y21R0021
P.VARALAXMI-13Y21R0036
N.VEDHAVATHI-13Y21R0046
B.Pharm 4th year 2nd sem
Under the Guidance of
G. HEMALATHA
ASSISTANT PROFESSOR
M.PHARM
KOTTAM INSTITUTEOF PHARMACY
ERRAVALLYXROAD

2. CONTENTS
 Introduction.
 Aim and objectives.
 Plan of work.
 Drug and excipients profile.
 Materials and equipments used.
 Methodology.
 Results and discussion.
 Summary and conclusion.
 Bibliography.

3. INTRODUCTION
Oral fast dissolving film is the type of drug delivery system
which when placed in the oral cavity, disintegrate or
dissolve with in a few seconds without the intake of water.

4. ADVANTAGES
As oral dissolving thin films are flexible , they are easy to
carry, store & handle.
Water Is not needed for administrating so problem
encountered in swallowing of tablets or capsules are evaded.
Enhanced stability .
Improved patient compliance.
DISADVANTAGES
High dose cannot be incorporated into the film.

5. OVER VEIW OF ORAL CAVITY
The cavity has the 2 regions
 Outer oral vestibule- which is
bounded by cheeks, lips, teeth.
 Oral cavity proper – which
extend from teeth and gum
back to fauces with the roof
comprising hard and soft
palate. Fig.1.Structure of oral cavity

6. The drug administered via the oral mucosa gain access to the
systemic circulation through a network of arteries and
capillaries.
The major artery supplying the blood to the oral cavity is
the external carotid artery.
The venous backflow goes through branches of capillaries
and veins and finally taken up by the jugular vein.
 Tongue projects from the floor of cavity.

7. Classification Of Fast Dissolve Technology
For ease of description, fast dissolve technology can be
divided in to three board groups:
 Lyophilized systems.
 Compressed tablet-based systems.
Thin film strips.

8. CLASSIFICATION OF ORAL FILMS
There are 3 types of oral films
 Flash release.
 Mucoadhesive melt away wafers.
 Mucoadhesive sustained release wafers.
One or combination of the following process can be used to
manufacture the mouth dissolving films
 Solvent casting.
 Semi solid casting.
 Hot melt extrusion.
 Solid dispersion extrusion.
 Rolling.
MANUFACTURING METHODS

9. AIM AND OBJECTIVES
AIM:
The aim of this present research work is to formulate and evaluate mouth
dissolving films using as a RISPERIDONE as model drug to improve
bioavailability and facilitating rapid onset to relieve from vomiting and
nausea.
At present RISPERIDONE is available as tablets and injections in the
market.
Patient are non cooperative to those dosage forms.
Hence fast dissolving drug delivery systems , because they are easy to
administer and lead to better patient compliance.

10. OBJECTIVES:
1. Selection of suitable drug candidate :
RISPERIDONE is selected as a suitable based on dose, molecular weight, solubility
oral bioavailability.
2. Selection of polymer:
HPMC E15 selected as polymer based on solubility and drug excipient compatibility.
3. To carry out the preformulations studies:
a. Plotting of calibration curve.
b. Solubility determination.
c. Physical incompatibility.
4. Formulation of RISPERIDONE oral disintegrating film was developed using by
solvent casting method.
5. To evaluate the developed formulation:
a. Weight variations.
b. Thickness uniformity.
c. Folding endurance.
d. Surface pH .
e . INVITRO disintegrating and dissolution test.

11. PLAN OF WORK
To carry out Preformulation studies:
1. Plotting of calibration curve
2. Solubility determination
3. Physical incompatible
Formulation of RISPERIDONE oral disintegrating film was developed using by
solvent casting method .
Evaluation of film formulations
a. Weight variations
b. Thickness uniformity.
c. Folding endurance
d. Surface pH
e. INVITROdisintegrating and
dissolution test

12. DRUG AND EXCIPIENT PROFILE
RISPERIDONE
Description:
 RISPERIDONE , a BENZISOXAZOLE derivative, is an
atypical antipsychotic drug with high affinity for 5-
hydrotryptamine (5-HT) and dopamine D2.
It is used primarily in the management of schizophrenia, in
schizophrenia,inappropriate behavior in severe dementia and
manic episodes associated with bipolar I disorder.
DRUG PROFILE

13. Physiochemical properties:
Chemical Formula : C23H27FN4O2
Molecular weight : 410.485 g/mol
Solubility : Risperidone is soluble in organic
solvents such as ethanol, DMSO, and dimethyl formamide
(DMF), which should be purged with an inert gas.
 Category : Antipsychotic agents.
Serotonin antagonists.
Dopamine antagonists.
Alpha 2 agonists.

14. Pharmacodynamics:
Risperidone is an atypical antipsychotic medication. It is most often
used to treat delusional psychosis (including schizophrenia), but
risperidone is also used to treat some forms of bipolar disorder and
psychotic depression. Risperidone is now the most commonly
prescribed antipsychotic medication in the United States.
Mechanism of action:
Blockade of dopaminergic D2 receptors in the limbic system
alleviates positive symptoms of schizophrenia such as hallucinations
delusions, and erratic behavior and speech. Blockade of serotonergic
5-HT2 receptors in the mesocortical tract, causes an excess of
dopamine and an increase in dopamine transmission, resulting in an
increase in dopamine transmission and an elimination of core
negative symptoms.

15. Absorption:
Well absorbed. The absolute oral bioavailability of risperidone is 70%
(CV=25%). The relative oral bioavailability of risperidone from a
tablet is 94% (CV=10%) when compared to a solution.
Volume of distribution:
1 to 2 L/kg
Protein binding:
Risperidone, ~88% bound; 9-hydroxyrisperidone, ~77% bound

16. Metabolism:
Extensively metabolized by hepatic cytochrome P450 2D6 isozyme to
9-hydroxyrisperidone, which has approximately the same receptor
binding affinity as risperidone. Hydroxylation is dependent on
debrisoquine 4-hydroxylase and metabolism is sensitive to genetic
polymorphisms in debrisoquine 4-hydroxylase. Risperidone also
undergoes N-dealkylation to a lesser extent.
Route of elimination:
Risperidone is extensively metabolized in the liver. In healthy elderly
subjects, renal clearance of both risperidone and 9-hydroxyrisperidone
was decreased, and elimination half-lives were prolonged compared to
young healthy subjects.

17.  Half life:
20-24 hours
Toxicity:
Symptoms of overdose include drowsiness, sedation, tachycardia ,
hypotension, and extra pyramidal symptoms. LD50=82.1mg/kg
(orally in mice).
Affected organisms:
Humans and other mammals

18. EXCIPIENT PROFILE
 Hypromellose (HPMC E15).
Category: polymer .
Propylene glycol.
Category: plasticizer.
Aspartame.
Category: Sweeting agent.

19.  Tween 80.
Category: nonionic surfactants & emulsifier .
Citric acid.
Category: Chelating agent.
 Sorbitol.
Category: Laxatives.
Flavoring agents (Pipperment).
Category: To mask the unpleasant odour .

20. MATERIALS AND EQUIPMENTS
USED
Following excipients were selected for the formulation after weeks of drug excipient
compatibility study using
S. No. Materials Source
1. Risperidone PharmaTrain, Hyderabad.
2. HPMC E15 S.D. Fine chemicals, Mumbai.
3. Propylene glycol S.D. Fine chemicals, Mumbai.
4. Sorbitol S.D. Fine chemicals, Mumbai.
5. Aspartame S.D. Fine chemicals, Mumbai.
6. Tween80 S.D. Fine chemicals, Mumbai.
7. Citric acid S.D. Fine chemicals, Mumbai.
8. Flavoring agent S.D. Fine chemicals, Mumbai.
Table No.1. List of Materials Used

21. EQUIPMENTS:
S . No Equipments Manufacturer/Supplier
1. Electronic Balance module-AUW 2200 Shimadzu Corporation, Japan.
2. pH Meter Metler Toledo, India.
3. UV-Visible Spectrophotometer (UV-
1601), (UV-2550)
Shimadzu-Corporation, Japan.
4. FT-IR Spectrophotometer 8300 Shimadzu-Corporation, Japan.
5. Humidity Chamber Thermo lab.
6. Dissolution Apparatus TDT-08L, Electro lab, India.
7. Filter (0.22μm) Millipore, UK.
8. Vernier Caliper Mitutoyo, Corps, Japan.
9. Disintegration Tester (USP) Electro Lab, India.
10. Hot Air Oven Servewell instruments.
11. Sonicator Sidilusonicator.
12. Gyratory Shaker Lab India.
Table No.2.List of Equipments Used

22. METHODOLOGY
Preformulation studies:
1.Calibration curve of in RISPERIDONE in 6.8pH Phosphate
buffer.
Preparation of 6.8pH phosphate buffer.
 Preparation of RISPERIDONE standard stock solution
(100µg/ml) in 6.8 pH phosphate buffer solution.
Determination of λ max of RISPERIDONE.
Calibration curve of RISPERIDONE in 6.8pH phosphate
buffer solution.
2. Solubility determination.

23. Formulation of Risperidone fast
dissolving films:
Mouth dissolving film of RISPERIDONE was prepared by solvent
casting technique.
Solution ‘A’ was prepared by dissolving HPMC-E15 polymer in 5 m
l of water.
Solution ‘B’ was prepared by dissolving RISPERIDONE, Aspartame,
SORBITAL & citric acid in 5 ml of ethanol.
The solutions ‘A’ and ‘B’ were mixed and stirred for 30min. and add
Propylene glycol and TWEEN 80 and Flavoring agent and continue
stirring for 10mins.
The solutions were cast on to glass Petri plate of 9 cm diameter and
were dried in the oven at 70°C till a peelable film was formed.
Then dried films were cut into rectangular shape pieces, with 4.0 cm2
(2.0 cm × 2.0 cm) total surface area.
Desired quantity of RISPERIDONE was 10 mg (dose of drug) per 4.0
cm2 films.

24. Ingredients F1 F2 F3 F4 F5 F6
Risperidone 0.5 0.5 0.5 0.5 0.5 0.5
HPMC E15 3 6 9 12 15 18
Propylene glycol 5 5 5 5 5 5
Sorbitol 56 53 50 47 44 41
Aspartame 5 5 5 5 5 5
Tween 80 5 5 5 5 5 5
Saliva stimulating
agent (citric acid)
5 5 5 5 5 5
Flavoring agent 0.5 0.5 0.5 0.5 0.5 0.5
Total wt(mg) 80 80 80 80 80 80
Table no.3.Formulation of RISPERIDONE FDF.

25. Evaluation of oral disintegrating films
1.Weight uniformity test.
2. Morphological properties.
3. Thickness of films.
4. Folding endurance.
5. Surface pH Drug.
6. Content uniformity test.
7. Invitro disintegration test.
8. Invitro dissolution studies.

26. RESULTS AND DISCUSSION
RESULTS:
RISPERIDONE oral disintegrating films were prepared by solvent casting method.
Total 6 formulations trials were finalized obtained by imparting concentration values
of polymer and plasticizer.
 The prepared films were evaluated further by different characterization tests.
Preformulation studies:
Calibration curve of RISPERIDONE in 6.8pH phosphate buffer solution:
Standard calibration curve of RISPERIDONE was drawn by plotting absorbance
versus concentration.
The λ max of Risperidone in 6.8pH phosphate buffer solution was found to be
299nm.

27. Fig 2. The λ max of Risperidone in 6.8pH phosphate buffer solution

28. S.NO CONC(mcg/ml) Absorbance*
1 0 0
2 1 0.147
3 2 0.314
4 3 0.481
5 4 0.624
6 5 0.789
*n=3
Table no.4.Calibration data of RISPERIDONE in 6.8pH phosphate buffer aλmax299nm
Fig.3.Standard calibration curve of RISPERIDONE in 6.8pH phosphate buffer
solution
y = 0.158x - 0.003
R² = 0.999
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 1 2 3 4 5 6
Absorbance
Concentration(µg/ml)
RISPERIDONE

29. Formulation
code F1 F2 F3 F4 F5 F6
Time 28sec 22sec 19sec 14sec 20 15
Appearance
film is
smooth
and clear
film is
smooth and
clear
film is
smooth and
clear
film is
smooth and
clear
slightly
hazy
slightly
hazy
Folding
endurance
20 18 17 15
19 22
Thickness
0.142mm 0.145mm 0.142mm 0.146mm 0.143mm 0.141mm
Table no.5. Evaluation parameters of RISPERIDONE FDF

30. Time in
min
% Drug released
F1 F2 F3 F4 F5 F6
0
0 0
0 0 0 0
5 54 51 48 65 55 62
10 68 59 55 81 67 75
15 79 69 71 92 84 87
20 89 87 86 96 93 94
30 94 91 92 98 96 97
Table no.6. In-vitro drug release data of formulation F1 to F6

31. Data analysis
For analyzing the mechanism of the drug release kinetics of the dosage form, the data
obtained were fitted to various kinetic equations of zero order, first order, for F1&F6.
The regression coefficient is calculated. Graphs of kinetic models were plotted with
suitable data.
0
20
40
60
80
100
120
0 5 10 15 20 25 30 35
%Drugreleased
Time(min)
Comparative dissolution profile for F1-F6
formulations F1
F2
F3
F4
F5
F6
Fig.4 Comparative dissolution profile for F1-F6 formulations

32. Fig.5. First order plot for F1-F6 formulations
0
0.5
1
1.5
2
2.5
0 5 10 15 20 25 30 35
Log%drugunreleased
Time(min)
First order plot for F1-F6 formulations
F1
F2
F3
F4
F5
F6

33. SUMMARY
Recently, fast dissolving drug delivery system have started gaining
popularity and acceptance as new drug delivery systems, because they
are easy to administer and lead to better compliance.
Fast-dissolving oral delivery systems are solid dosage forms, which
disintegrate or dissolve within 1 min when placed in the mouth without
drinking or chewing.
 Risperidone is suitable drug candidate to formulate in to FDF, HPMC
E15 were selected as polymers, propylene glycol as plasticizers
aspartame as sweetener, and pipperment as a flavor was included, and
formulation was developed based on the plasticizer and polymer
concentration. Thus prepared films are evaluated for thickness, weight
variation, assay, surface PH, folding endurance, disintegration
time, invitro dissolution, release order kinetics (zero order and first
order) were applied for optimized formulation F1-F6.

34. Risperidone orally disintegrating films were successfully prepared
with HPMC E15CSPS.
The amount of plasticizer propylene glycol was critical for film
formulation and separation properties.
Taste masking was achieved using combination of sweetener
aspartame and pipperment flavor.
Propylene glycol was selected for solubility enhancer during shelf life
period.
Type of flavoring agent was critical for producing taste masking of
mouth dissolving film.
Acceptable mechanical properties were obtained in the batch F4 and
the in-vivo disintegrating time was below 20 sec.
It was concluded that formulations F-4 were found to be satisfactory
batch and were optimized for the desirable properties.
CONCLUSION

35. BIBLIOGRAPHY
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by Anne Waugh and Allison Goraw published by Churchill Livingstone
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37. THANK
YOU