oral films of Metoclopramide HCl using various polymers

1. FORMULATION & EVALUATION OF FAST
DISSOLVING ORAL FILM
Prepared & presented by:
Mr. Gajanan A. Shete
Guide: Miss. Kadam V.S.
Assistant Professor
Indira Colleg e of Pharmacy,
Vishnupuri, Nanded.
Indira college of pharmacy, Vishnupuri.
1
Seminar on

2. CONTENTS
 Introduction
 Aim & Objective
 Plan of work
 Literature review
 Material & method
 Result & discussion
 Summary and Conclusion
 Reference 2

3. INTRODUCTION
Fast Dissolving Oral Film: It is a thin oral strip of
hydrophilic polymers which rapidly dissolves on the
tongue or in the buccal cavity.
Figure no.1: Fast dissolving oral film 3

4. Fast dissolving drug delivery systems were first developed in
the late 1970s as an alternative to conventional dosage forms
for pediatric and geriatric patients who experience difficulties
in swallowing traditional oral solid-dosage forms.
This delivery system consists of a thin film, which is simply
placed on the patient’s tongue or mucosal tissue, instantly wet
by saliva; the film rapidly dissolves.
Then it rapidly release the medication for oral mucosal
absorption.
4

5. These are also called as:-
 Oral thin films
 Mouth dissolving films/strips.
 Buccal films/strips.
 Fast dissolving films.
 Oral strips.
5

6. SPECIAL FEATURES
 Thin elegant film
 Available in various sizes & shapes
 Unobstructive
 Excellent mucoadhesion
 Rapid release
6

7.  It can be administered
without water.
 Rapid disintegration
 Thin, flexible, portable
 Suitable for pediatric,
geriatric patients.
 Minimized first pass
effect.
ADVANTAGES DISADVANTAGES
 Large dose can not incorporated
Some films may be temperature
/ moisture sensitive.
7

8. Formulation
A typical composition contains the following drug
 Drug - 5% to 30% w/w
 Water soluble polymer - 45% w/w
 Plasticizers - 0 to 20% w/w
 Surfactants - quantity sufficient
 Sweetening agents - 3 – 6%w/w
 Saliva stimulating agent - quantity sufficient
 Colouring agents - quantity sufficient
 Flavouring agents - quantity sufficient 8

9. Manufacturing
methods
Solvent
casting
Hot melt
extrusion
Solid
dispersion
method
Semi
solid
casting
Rolling
method
9

10. AIM & OBJECTIVE
Aim:
Formulation & evaluation of fast dissolving oral films.
Objective:
 The main objective of the present study is to formulate and
evaluate fast dissolving oral films (FDOFs) .
 To study the effect of different polymers on the release of drug
from fast dissolving film.
 To study the effect of different plasticizer on mechanical
properties of fast dissolving film.
10

11. PLAN OF WORK
1.Literature review
2.Selection of drug and excipients
3.Procurement of drug and excipients
4.Preformulation study of Drug
 Drug excipients compatibility studies
 Melting point determination
 Preparation of standard cure of using UV-Visible spectroscopy
 Solubility 11

12. 5. Formulation
 Dose calculations
 Exploration of polymers for preparation of films
 Selection of Plasticizer for optimization of films
6. The films will be evaluated for following parameters.
 Appearance
 Thickness
 Weight variation
 Folding endurance
12

13.  pH of film
 Tack test/Dry test
 Drug content uniformity
 Disintegration time
 In-vitro dissolution test
7. Result & Discussion
13

14. LITERATURE SURVEY
Sr.
No.
Author Title Polymer and other
constituents
1 Chinmay
Shrimali. et
al.
Formulation and
evaluation of fast
dissolving films of
Meloxicam
PVA, PEG-400,
Glycerol, Aspartame,
Citric acid.
2 Swati G.
Talele. et al.
Formulation and
evaluation of mouth
dissolving films of
Almotriptan malate
HPMC E‐15, HPMC
E‐4, Gelatin, PEG
400,Aspartame,
Sodium Starch
glycolate
14

15. Sr.
No.
Author Title Polymer and other
constituents
3 Rama K.
Krishna. et
al.
Formulation and
evaluation of oral
disintegrating films
of loratidine
HPMC E3, E6,
Pullulan, PEG 400,
4 Amit E.
Birari. et
al.
Formulation and
evaluation of oral
disintegrating films
of atenolol
HPMC, PVA,
Glycerin, Vanillin,
SLS,
5 Dr. Aruna
Kumari. et
al.
Formulation and
evaluation of fast
dissolving oral films
of Losartan
potassium
HPMC, PVA,
PVPK30,
Maltodextrin,
glycerol, 15

16. DRUG PROFILE
Metoclopramide HCl
 IUPAC Name:4-amino-5-chloro-N-[2(diethylamino)ethyl]-
2methoxybenzamide hydrochloride
 Molecular formula: C14H23Cl2N3O2
 Molecular weight: 354.3 gm/mol
 Synonym: Maxolon, Reglan
 Description: white crystalline, odorless substance
16

17.  Solubility: Freely soluble in water & ethanol
 Half life: 5-6 hours
 Category: Antiemetic.
 Bcs class: III
 Melting point: 1830c
 Dose of drug: 10 mg
17

18. Sr. no. Name of the ingredient Name of supplier / manufacturer
1 Metoclopramide HCl Ipca laboratories, India.
2 HPMC E-5, E15, K4M,
K15
Ajanta pharma, Mumbai.
3 Maltodextrin Ajanta pharma, Mumbai.
4 Xanthum gum Moly Chem. Pvt. Ltd, Mumbai.
5 Guar gum Moly Chem. Pvt. Ltd, Mumbai.
6 Polyethylene glycol 400 Research-Lab fine Chem. Ind, Mumbai
7 Glycerol Moly Chem. Pvt. Ltd, Mumbai.
8 Saccharin Hindustan chemicals & pharma, Mumbai.
List of chemicals and their suppliers
18
Table no-1:List of chemicals and their suppliers

19. PREFORMULATION STUDY
19
Preformulation
study
Melting
point
FTIR
study
UV
Spectrum
Solubility

20. MELTING POINT
Melting point of Metoclopramide HCl was found to be 1800.
Thus it indicates the purity of sample which compiles with
standard and standard melting point was 1830c.
Solubility
Solubility of drug was checked in water and ethanol. Drug was
freely soluble in water and ethanol. 20
Method Melting point
Capillary method 1800c

21. UV SPECTRUM
Figure no.2 : UV spectrum of Metoclopramide HCl
The λ max of metoclopramide HCl was found to be 272 nm in
Phosphate buffer (pH 6.8).
21

22. Calibration curve of Metoclopramide HCl in
Phosphate buffer (pH 6.8)
Sr. no.
Concentration in µg/ml Absorbance at 272 nm
1 4 0.157
2 8 0.276
3 12 0.429
4 16 0.540
5 20 0.654
6 24 0.827
7 28 0.948 22
Table no-2:Calibration curve of Metoclopramide HCl in Phosphate buffer

23. Regression equation=Y=0.033x+0.010
Correlation coefficient (R2)=0.998
y = 0.033x + 0.010
R² = 0.998
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 4 8 12 16 20 24 28 32
Metoclopramide HCl
Absorbance at 272
nm
Absorbance
Concentration (µg/ml)
23

24. Calibration curve of Metoclopramide HCl in 0.1N HCl
Sr.no. Concentration in µg/ml Absorbance at 272 nm
1 2 0.078
2 4 0.150
3 6 0.232
4 8 0.296
5 10 0.374
6 12 0.440
7 14 0.525
8 16 0.589
9 18 0.661
10 20 0.731
11 22 0.811
12 24 0.874
13 26 0.941
24
Table no-3:Calibration curve of metoclopramide HCl in 0.1 N HCl

25. Regression equation=Y=0.036x+0.007
Correlation coefficient (R2)=0.999
y = 0.036x + 0.007
R² = 0.999
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Metoclopramide HCl
Absorbance at 272
nm
Absorbance
Concentration (µg/ml)
25

26. DRUG EXCIPIENT COMPATIBILITY
STUDY
FTIR Study
26

27. Functional group Wave number (cm-1)
Aliphatic C-H stretch 2879 cm-1
Amide C=O stretch 1648 cm-1
Aromatic C=C stretch 1550 cm-1
Amine N-H stretch 3449 cm-1
27
Table no-4: IR peaks of various functional groups of Metoclopramide HCl

28. HPMC E5 Metoclopramide HCl+HPMC E5
HPMC E15 Metoclopramide HCl+HPMC E15
28

29. HPMC K4M Metoclopramide HCl+HPMC K4M
HPMC K15M Metoclopramide HCl+HPMC K15M29

30. TRAIL BATCH
Polymer
Drug Polymer
quantity
PEG-400 Glycerin
Sacchari
n
DW
(ml)
HPMC 70mg 100mg 50mg 20mg Qs
Xanthum
gum
70mg 100mg 50mg 20mg Qs
Guar gum 70mg 30mg 50mg 20mg Qs
Maltodextrin 70mg 30mg 50mg 20mg Qs
HPMC 70mg 100mg 50mg 20mg Qs
Xanthum
gum
70mg 100mg 50mg 20mg Qs
Guar gum 70mg 30mg 50mg 20mg Qs
Maltodextrin 70mg 30mg 50mg 20mg Qs
30

31. FORMULATION CONSIDERATIONS
 Dose calculation
Diameter of the plate = 6 cm
Area of the plate = πr2 =28.26 cm2
No of 4 cm2 films present in whole plate = 28.26/4 s = 7.065
Each film contains 10 mg of drug.
The amount of drug to be loaded in each plate was =7.065 x 10
=70.65 mg
31

32. Exploration of polymers for preparation of films
Fast dissolving oral films were prepared by using various
polymers like different grade of HPMC, Xanthum gum, Guar
gum, Maltodextrin.
Selection of plasticizer for optimization of films
PEG-400 and Glycerol used as plasticizers.
PEG-400 has higher film forming capacity, films formed were
transparent and non-tacky.
32

33. FORMULATION
The fast dissolving oral film was prepared by dissolving (HPMC grade) film
forming polymer in the distilled water (Qs) then solution was continuously
stirred up to 15 min and kept aside for 5 min to remove all the air bubbles
entrapped. Meanwhile, in the separate container remaining excipients i.e.
plasticizer PEG-400 and sweetener saccharin along with drug were dissolved in
distilled water (Qs) with constant stirring for 15 min. when the stirring was over
both the solution were mixed together and stirred for another 15 min. Then the
solution was kept stationary for 10 min to remove the air bubbles. The
formulation was casted on a suitable platform and dried to form a film. The film
was dried in the oven then the film was carefully removed and cut into suitable
size i.e. 2cm X 2cm.
33

34. Trial code
Metoclopr
amide
HCl
HPMC E-
5
HPMC E-
15
HPMC K-
4M
HPMC K-
15
PEG-400 Saccharin D.W.
F1 70.65 100 ---- ---- ---- 50 20 Qs
F2 70.65 200 ---- ---- ---- 50 20 Qs
F3 70.65 300 ---- ---- ---- 50 20 Qs
F4 70.65 ---- 100 ---- ---- 50 20 Qs
F5 70.65 ---- 200 ---- ---- 50 20 Qs
F6 70.65 ---- 300 ---- ---- 50 20 Qs
F7 70.65 ---- ---- 100 ---- 50 20 Qs
F8 70.65 ---- ---- 200 ---- 50 20 Qs
F9 70.65 ---- ---- 300 ---- 50 20 Qs
F10 70.65 ---- ---- ---- 100 50 20 Qs
F11 70.65 ----- ---- ---- 200 50 20 Qs
F12 70.65 ---- ---- ---- 300 50 20 Qs
34

35. RESULT AND DISCUSSION
In the following table results for film forming capacity,
Tack test and Appearance given.
Film forming capacity was divided in three categories
according to there film forming capacity i.e. Good, Better,
Best.
All films prepared were transparent and only 2 batches were
found to be tacky.
35

36. Formulation
batch
Film forming
capacity
Tack test Appearance
F1 Good Tacky Transparent
F2 Best Non tacky Transparent
F3 Better Non tacky Transparent
F4 Good Tacky Transparent
F5 Best Non tacky Transparent
F6 Better Non tacky Transparent
F7 Good Non tacky Transparent
F8 Better Non tacky Transparent
F9 Better Non tacky Transparent
F10 Good Non tacky Transparent
F11 Better Non tacky Transparent
F12 Better Non tacky Transparent
36

37. Batch
Disintegration time
(Sec)
Folding endurance % drug content
F1 16.6±0.57 15.0±1.00 90.03±1.7
F2 21.3±0.57 42.3±0.57 98.53±1.09
F3 30.3±0.57 51.6±0.57 91.41±0.13
F4 26.0±1.00 14.3±0.57 92.87±0.76
F5 30.0±1.73 41.3±0.57 93.5±0.82
F6 33.6±0.57 58.6±0.57 89.03±0.09
F7 27.0±1.00 15.3±1.15 93.13±1.2
F8 39.0±0.00 37.3±0.57 92.7±0.38
F9 47.3±0.57 56.0±0.00 91.43±0.71
F10 26.3±1.52 20.0±1.00 90.36±1.55
F11 36.6±0.57 47.6±1.15 92.33±0.27
F12 48.3±0.57 58.6±0.57 91.44±0.98
37

38. Batch Weight variation
(mg)
Film thickness
(mm)
pH
F1 12 0.7 6.6±0.01
F2 16 0.8 6.8±0.03
F3 22 1 6.7±0.06
F4 13 0.8 6.5±0.02
F5 16 0.9 6.4±0.05
F6 24 1 6.7±0.05
F7 13 0.8 6.5±0.11
F8 18 1 6.7±0.17
F9 27 1.1 6.7±0.02
F10 13 0.8 6.6±0.15
F11 18 1 6.5±0.15
F12 26 1.2 6.6±0.02
38

39. Time
(min)
F1 F2 F3 F4 F5 F6
1 22.45±0.12 18.27±0.39 17.05±0.21 21.35±0.29 19.59±0.16 14.53±0.28
2 34.54±0.13 27.52±0.37 25.07±0.46 32.7±0.22 29.24±0.29 20.35±0.43
3 46.47±0.15 29.98±0.41 29.22±0.41 40.88±24 38.64±0.33 28.62±0.16
4 53.61±0.14 37.02±0.49 34.59±0.31 54.7±03 42.87±0.65 36.42±0.35
5 63.22±0.31 48.29±0.54 46.65±0.47 67.52±0.32 64.49±0.35 46.47±0.28
6 72.62±0.29 57.98±0.12 55.69±0.19 74.65±0.32 71.49±0.43 52.3±0.45
7 78.56±0.31 62.98±0.45 62.46±0.14 81.29±0.43 77.53±0.39 63.45±0.39
8 82.1±0.47 83.88±0.76 78.63±0.36 88.21±0.28 83.74±0.23 72.26±0.40
9 85.96±0.22 92.83±0.39 85.57±0.34 89.24±0.34 89.41±0.26 84.48±0.36
10 91.26±0.40 99.81±0.09 92.45±0.29 94.59±0.33 93.59±0.17 91.4±0.3
% Cumulative drug release
39

40. Time
(min)
F7 F8 F9 F10 F11 F12
1
23.53±0.23 22.32±0.55 16.08±0.79 21.21±0.74 17.84±0.64 14.37±0.41
2
34.18±0.56 30.94±0.49 23.04±0.22 29.56±0.18 26.91±0.32 22.33±0.08
3
43.27±0.04 44.46±0.98 32.08±0.46 36.78±0.07 38.53±0.41 31.67±0.44
4
55.65±0.79 57.65±0.12 42.75±0.89 41.55±0.28 41.18±0.62 40.61±0.66
5
62.02±0.67 60.32±0.36 52.43±0.07 49.78±0.66 51.88±0.77 48.33±0.33
6
68.02±0.34 70.27±0.49 58.95±0.71 57.89±0.34 56.49±0.86 54.89±0.07
7
84.58±0.92 81.50±0.86 66.92±0.38 69.45±0.67 68.93±0.43 65.21±0.71
8
59.08±0.88 87.63±0.35 73.34±0.96 77.27±0.33 74.36±0.11 71.96±0.61
9
94.02±0.07 92.15±0.73 85.20±0.21 86.45±0.41 83.47±0.18 81.45±0.37
10
96.55±0.39 95.47±0.08 90.64±0.77 94.63±0.55 90.58±0.32 88.33±0.18
40

41. 0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10
F7
F8
F9
Time (min)
%CDR
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10
F10
F11
F12
Time (min)
%CDR
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10
F1
F2
F3
Time (min)
%CDR
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10
%CDR
Time (min)
F4
F5
F6
41

42. SUMMARY
 Metoclopramide HCl used for the treatment of nausea and
vomiting, hence the attempt had been made to develop oral fast
dissolving films of Metoclopramide HCl by solvent casting
method.
 Different polymers were used for fast dissolving films, such as
Xanthum gum, Guar gum, Maltodextrin, HPMC E5, E15, K4M,
and K15. Films cannot be formed using Xanthum gum, Guar gum
as polymer. Films using Maltodextrin as polymer formed but it
cannot be removed whole from petri plate. It gets teared while
removing from surface of petri plate.
42

43. So Xanthum gum, Guar gum and Maltodextrin were not
used for further study.
 PEG 400 and glycerol were used as plasticizer for film
formation. In case of PEG 400 films were formed and can be
easily removed from petri plate. Films were transparent in
appearance. When glycerol was used as plasticizer films
were not formed, so it cannot be used for further study.
43

44. CONCLUSION
 For the present study, Metoclopramide HCl was selected as a
model drug candidate as no marketed film of Metoclopramide
HCl is available in India.
 The FTIR study revealed that there were no any considerable
changes in peaks of drug and polymer complex.
 The λ max of metoclopramide HCl was found to be 272 nm in
Phosphate buffer (pH 6.8).
 The fast dissolving oral film prepared by solvent casting
method with different film forming polymers as HPMC-E5,
E15, K4M, K15 and plasticizer PEG 400.
44

45.  All the formulations were evaluated for their Appearance,
thickness, folding endurance, disintegration time, pH, Tack test,
drug content uniformity and drug release characteristics . All
results found to be precise.
 % cumulative drug release of batch F2 was found to be 99.81%
in 10 minutes and it was the best when compared to other.
Disintegration time of F2 batch was found to be 21 sec. The
% drug content of F2 batch was found to be 98.53%, hence F2
batch was the best batch when compared to others.
 pH of optimized batch was found to be 6.8.
45

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50

51. Thank you
51