Formulation and evaluation of mouth dissolving film containing antiemetic drug for the treatment of motion sickness

FORMULATION AND EVALUATION OF MOUTH DISSOLVING FILM
CONTAINING ANTIEMETIC DRUG FOR THE TREATMENT OF MOTION
SICKNESS
Presented by:- SIDDHANT THAKUR
(Roll No.: 1717256514
(M. Pham (Pharmaceutics)
23-Jun-20

MOUTH DISSOLVING FILMS
 Mouth dissolving films are placed over the tongue it rapidly hydrate, disintegrates
and dissolve to release the medicament in the oral cavity.
 The drug enters into systemic circulation without passing through hepatic first
pass metabolism, this lower dosing interval, improves onset of action, efficacy
and safety profile of therapy.
 These films are thin and flexible by their nature.
 These films are excellent for targeting sensitive site that may not be possible with
tablets or liquid formulation.
 Accuracy in the administer dose is assured.
 There is no need of water hence no risk of chocking.
 Similarly they are useful in eliminating side effects of the drug
23-Jun-20

LITERATURE REVIEW
 The exhaustive literature on development of Mouth dissolving films was
reviewed from the following sources: journals, e- journals, Patents etc.
Searching from websites: www.google.co.in
www.sciencedirect.com
www.pubmed.com
www.spinger.co.in
www.elsewier.com
www.sci_hub.com

STATEMENT OF RESEARCH PROBLEM
Motion sickness is a common condition that occurs in peoples who travel by car,
train, airplane or boat etc. It progresses from a feeling of uneasiness
to sweating and/or dizziness which is quickly followed by nausea or vomiting.
Motion sickness is treated by using antiemetic drugs. The major problems with
conventional oral therapy of antiemetic drugs are;
 Motion sickness patient require a rapid onset action, cannot be achieved by
conventional therapy.
 Low bioavailability due to incomplete absorption and hepatic first pass
metabolism of the drug.
 Paediatric, geriatric and psychiatric patients have difficulty in swallowing are
unwilling to take conventional dosage form which lead to chocking.
To overcome these problems and fulfil these medical needs, mouth dissolving
films based drug delivery system is developed.
23-Jun-20

OBJECTIVES OF THE STUDY
• To formulate MDFs of Drug containing antiemetic drug (Ondansetron
HCL) by using DOE
• To characterize the prepared MDFs of the drug. Evaluation parameters
like: Folding endurance, surface pH, Weight uniformity etc.
• To optimize the above said evaluation parameters by using DOE 11 and
perform in-vitro dissolution studies on the optimized MDFs
• FT-IR of the developed MDFs

PLAN OF RESEARCH WORK
1. Literature Review
2. Selection of Drug
3. Preformulation Studies
 Identification of drug
 Physical Properties
 Melting Point
 Fourier Transform Infrared Spectroscopy (FT-IR)
 Preparation of Calibration curve of drug
4. Formulation of Mouth Dissolving Films (Ondansetron Hydrochloride)
5. Evaluation of MDFs
 Morphological Properties
 Folding Endurance
 Surface pH
 Weight Uniformity
 Folding Endurance
 Thickness
 Tensile Strength
 Effect of Formulation variables on In vitro Disintegration test
 Effect of Formulation variables on Percentage Drug content
6. Optimization of Formulation
7. In vitro Dissolution studies of the Optimized formulation
8. FT-IR of MDFs of Ondansetron Hydrochloride

2. SELECTION OF DRUG……
Ondansetron
hydrochloride
Ondansetron
hydrochloride
Pharmacology
Need for the
development of
MDF of Ondasetron
HCl with the
following purpose
Drug enter into systemic circulation.
Avoid Hepatic first pass metabolism
This increase the bioavailability of drug.
To reduce the dosing frequency.
This leads to the reduction in side effects and
improve patient compliance
Anti- emetic activity .
 For the treatment of post-operative nausea
and vomiting.
 Also for Chemotherapy induced nausea and
vomiting or Radiation induced nausea and
vomiting.
its short half-life that ranges from 3 to 5 h.
 it has a oral bioavailability of 60% due to hepatic
first pass metabolism

Preformulation
studies
Identification of Drug
FT-IR of the Drug
Preparation of calibration
curve of Ondansetron
HCL

IDENTIFICATION OF DRUG (ONDANSETRON HYDROCHLORIDE)
Physical
appearances
 Obtained as a gift sample from Beaukev Pharma
International Pvt. Ltd, Mumbai, India.
 White or almost white powder.
Determination
of Melting
point
Determined by capillary fusion method.
 M.P. was found to be 178 ± 1⁰C, which
complied with reported value (178.5 -179.5 ⁰C)
in Merck index.

FOURIER TRANSFORM INFRARED SPECTROSCOPY (FT-IR)
STUDY
Reference FT-IR spectra of
ondansetron hydrochloride(IP 2010)
Obtained FT-IR spectra of Drug
S.NO. Named group Reported band
frequencies (cm-1)
Band frequency obtained
(cm-1)
1 Aromatic C― H
(Stretching)
3000 - 3500 3398.62
2 C = O 1750 - 1600 1632.74
3 C = N 1250 -1500 1475.11
4 C ― CL 800 - 600 749.24

UV-ABSORPTION MAXIMA OF ONDASETRON HYDROCHLORIDE
Concentration 1 2 3
Mean
Absorbance
0 0 0 0 0
2 0.101 0.102 0.101 0.101
4 0.204 0.203 0.205 0.204
6 0.299 0.300 0.298 0.299
8 0.399 0.398 0.399 0.399
10 0.492 0.493 0.494 0.493
12 0.589 0.590 0.590 0.590
14 0.699 0.700 0.698 0.699
16 0.810 0.811 0.809 0.810
18 0.910 0.912 0.913 0.912
20 0.995 0.996 0.994 0.995
Standard plot of ondansetron HCL in
water at 310nm
S.No Solvent
system
(R2) Slope Intercept
1. Distilled
water
0.9996 0.0501 0.0011
UV-Absorption
maxima((λ max)
 Drug solution (100 μg/ml) in Distilled water was scanned
b/w ranges from 200-400 nm.
 λmax was found to be 310 nm, matched with reported in Research
paper (Ondasetron HCl orodispersible tablet).
 Beer Lambert law limit of the ondansetron HCL lie between 0- 20
µg/ml
y = 0.0501x - 0.0011
R² = 0.9996
0
0.2
0.4
0.6
0.8
1
1.2
0 2 4 6 8 10 12 14 16 18 20
Absorbance Concentration (µg/ml)

Standard plot of ondansetron HCL in PBS pH 6.8 at 310nm
Concentration 1 2 3
Mean
Absorbance
0 0 0 0 0
2 0.079 0.080 0.081 0.080
4 0.182 0.183 0.184 0.183
6 0.268 0.268 0.271 0.269
8 0.372 0.371 0.372 0.372
10 0.484 0.482 0.483 0.483
12 0.545 0.546 0.547 0.546
14 0.653 0.652 0.651 0.652
16 0.730 0.728 0.731 0.730
18 0.832 0.831 0.831 0.831
20 0.910 0.911 0.912 0.911
y = 0.0461x - 0.0012
R² = 0.9990
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
Absorbance
Concentration (µg/ml)
S.No Solvent system (R2) Slope Intercept
1. PBS pH(6.8) 0.9990 0.0461 0.0012

DESIGN
EXPERT 11
Factors HPMC E5 HPMC E15 PVP K30
Variables 1% 1.5% 2%
Citric acid, Sodium saccharin, and drug concentration are kept constant.
Dose Incorporated in the film = Area of petridish x Dose of the drug
Area of film .
Composition used for the preparation
of mouth dissolving films is prepared
by the use of design expert 11.

FORMULATION COMPOSITION OF MOUTH DISSOLVING FILM OF
ONDASETRON HYDROCHLORIDE
Formulatio
n code
HPMC E 5
(%w/v)
HPMC 15
( %w/v)
PVP K-30
(%w/v)
Citric Acid
(mg)
Sodium
saccharin
(mg)
PEG 400
(ml)
Drug
(mg)
MDF 1 1 2 1.5 10 10 3 64
MDF 2 1.5 2 2 10 10 3 64
MDF 3 2 2 2 10 10 3 64
MDF 4 2 1 1 10 10 3 64
MDF 5 1 1 1.5 10 10 3 64
MDF 6 1.5 1.5 2 10 10 3 64
MDF 7 1.5 2 1.5 10 10 3 64
MDF 8 1 1.5 1 10 10 3 64
MDF 9 1 1.5 1.5 10 10 3 64
MDF 10 2 1 2 10 10 3 64
MDF 11 2 1.5 2 10 10 3 64
MDF 12 1.5 1.5 1 10 10 3 64
MDF 13 2 2 1 10 10 3 64

Formulation
code
HPMC E-5
(%)
HPMC E-15
(%)
PVP K-30
(%)
Citric Acid
(mg)
Sodium
saccharin
(mg)
PEG 400
(ml)
Drug
(mg)
MDF 14 1.5 1 1 10 10 3 64
MDF 15 1 1.5 2 10 10 3 64
MDF 16 1.5 1.5 1.5 10 10 3 64
MDF 17 2 1 1.5 10 10 3 64
MDF 18 1.5 2 1 10 10 3 64
MDF 19 1.5 1 2 10 10 3 64
MDF 20 1 2 1 10 10 3 64
MDF 21 2 1.5 1.5 10 10 3 64
MDF 22 1 2 2 10 10 3 64
MDF 23 2 1.5 1 10 10 3 64
MDF 24 1 1 2 10 10 3 64
MDF 25 1 1 1 10 10 3 64
MDF 26 1.5 1 1.5 10 10 3 64
MDF 27 2 2 1.5 10 10 3 64

PREPARATION OF MOUTH DISSOLVING FILMS
Solvent casting method
Polymeric
solution is
prepared
Drug and
excipients
are added
Homogenized
by magnetic
stirrer
Cast on a
Petri dish
Dried in hot air
oven at 60⁰C
for 24 hrs

EVALUATION OF MOUTH DISSOLVING FILMS
Morphological
properties
• Color :- Colorless
• Transparency :– Transparent
• Surface :- Smooth
Surface pH of film was found to be in
range of 6.70 ± 0.015 to 6.82 ± 0.01,
ideally it should be in the range of 6.2
- 7.00.
Surface pH
Weight
Uniformity
Weight of film found to be in range
93 ± 1 to 236 ± 1.

Tensile
strength
Thickness of
the film
Folding
endurance
Tensile strength of film found to be in
range 0.426 – 1.304 Kg/mm² .
• Thickness of film found to be in
range 0.064 -0.366mm.
•Thickness effect the disintegration time of
film.
Folding endurance of film > 300, for
good film it should be in range of
250 - 300.

Form.
Code
Color Transparency Surface
Folding
Endurance
Mass uniformity
(mg)
Thickness (mm)
Tensile Strength
(Kg/mm²)
MDF-1 Colorless Transparent Smooth >300 167.00± 1.00 0.160± 0.04 0.634± 0.018
MDF-2 Colorless Transparent Smooth >300 192.00± 1.00 0.211± 0.05 0.701 ± 0.008
MDF-5 Colorless Transparent Smooth >300 134.00± 1.00 0.064±0.02 1.168 ± 0.014
Physico-chemical Evaluation of Ondansetron Hydrochloride MDFs

EFFECT OF FORMULATION VARIABLES ON IN- VITRO DISINTEGRATION
TEST
In-vitro disintegration test is performed by petridish method. The film in disintegrated in 25
ml phosphate buffer having pH 6.8, and the time at which film breaks is recorded.
Disintegration time of the films is found to be in range of 19.66 ± 2.51 to 65.66 ± 6.02 sec.
(a) Initial Film (b) Final Film
On application of factorial design, quadratic model was proposed by Design expert 11. The
model response R1 (Disintegration time) is as follows:
R1= +37.92+ 7.39A +7.13B +3.35C Eq.-1
The above Eq.-1 + sign indicates that the A (concentration of HPMC E5), B (concentration of
HPMC E15), and C (concentration of PVP K30) has flattering effect on disintegration
time.
Thus increase in A (HPMC E5), B (HPMC E15) and C (PVP K30) concentration led to
increase the disintegration time of film.

Two dimensional (2D) contour plot of response R1
(Disintegration time)
Three dimensional (3D) response surface plots for response
R1 (Disintegration time)

EFFECTS OF FORMULATION VARIABLES ON % DRUG CONTENT
 The % drug content in the MDFs having ondansetron hydrochloride was
measured using UV spectrophotometer. The % drug content of all the MDFs
was figure out to be in the limit of 55.50 ± 0.50 % to 95.83 ± 0.76 %.
 Formulation MDF-5, MDF-24 and MDF-25 show the highest % drug
content. On application factorial design quadratic model was proposed by
DOE 11. The model response R2 (Percentage drug content) is as follows:
R2= +71.50- 4.64A- 7.41B- 3.61C+ 7.20B² Eq.- 2
 In above Eq. (2), – sign of factor A (HPMC E5), B (HPMC E15) and C
(PVP K30) has negative impact on percentage drug content, + sign indicate
that factor B2 indicates that it has positive effects on percentage drug
content.

Two dimensional (2D) contour plot for response R2
(% Drug content)
Three dimensional (3D) response surface plots for
response R2 (% Drug content)

Run
Formulation
code
Factor 1
A:HPMC E5
Factor 2
B:HPMC E15
Factor 3
C:PVP K30
Response 1
Disintegration
Time
(Second)
Response 2
Drug Content
(%)
1 MDF-1 1 2 1.5 37.33 68.67
2 MDF-2 1.5 2 2 48.66 65.33
3 MDF-3 2 2 2 35 80
4 MDF-4 2 1 1 40 67.17
5 MDF-5 1 1 1.5 27.67 93.5
6 MDF-6 1.5 1.5 2 48 63
7 MDF-7 1.5 2 1.5 34.66 77.5
8 MDF-8 1 1.5 1 21 89.17
9 MDF-9 1 1.5 1.5 35.66 69.67
10 MDF-10 2 1 2 40 67.67
11 MDF-11 2 1.5 2 64 65.33
12 MDF-12 1.5 1.5 1 38.33 65
13 MDF-13 2 2 1 55.33 55.5
14 MDF-14 1.5 1 1 28.33 88.83
Experimental design layout of Ondansetron Hydrochloride MDFs

15 MDF-15 1 1.5 2 36.66 67.5
16 MDF-16 1.5 1.5 1.5 38.33 71
17 MDF-17 2 1 1.5 37.33 73.83
18 MDF-18 1.5 2 1 38.33 76.33
19 MDF-19 1.5 1 2 38.66 83.33
20 MDF-20 1 2 1 29.66 86.5
21 MDF-21 2 1.5 1.5 33.33 82.33
22 MDF-22 1 2 2 47.33 69.17
23 MDF-23 2 1.5 1 53 70.5
24 MDF-24 1 1 2 23.33 94.83
25 MDF-25 1 1 1 19.66 95.83
26 MDF-26 1.5 1 1.5 31 83.67
27 MDF-27 2 2 1.5 65.66 62.67
23-Jun-20

5. OPTIMIZATION OF FORMULATION
Optimization of
Formulation
Percentage Drug
content
Disintegration
time
23-Jun-20

 If the disintegration time of the mouth dissolving film is high it may not
provide rapid relief from the symptoms for which it is used. Also if the
percentage drug content of the film is less, then the film may not release the
required amount of drug into systemic circulation to produce their effect.
Hence the formulation displaying disintegration time in the limit between
(10-30 sec), desired percentage drug release more than 85%, selected as
optimized formulation.
 Formulation MDF-5, MDF-8, MDF-14, MDF-20, MDF-24and MDF-25
shows all these desirable characteristics, thus all these formulations was
taken as optimized formulations and was proceeds to In-vitro dissolution
studies in order to find out the drug release in PBS having pH 6.8.
23-Jun-20

IN-VITRO DISSOLUTION STUDIES OF THE OPTIMIZED
FORMULATIONS
 The in-vitro dissolution tests on all the optimized formulated were
performed by using PBS having pH 6.8 at 37± 0.5˚C at 50 rpm.
Aliquots were taken at every 10 seconds and at the same time
replaced with fresh dissolution medium. Maximum in-vitro drug
release was find out to be 95.80 % over a period of 120 sec (2 min)
while minimum in-vitro drug release was found to be 85.76 %.
Among all the optimized formulations, the best formulation was
found to be MDF-25 which containing HPMC E5 (1%), HPMC
E15 (1%) and PVP K30 (1%). Because this formulation shows
lesser disintegration time (19.66 sec) and faster drug release within
120 sec (95.80%).
23-Jun-20

Time (sec)
% Drug Release
MDF-5 MDF-8 MDF-14 MDF-20 MDF-24 MDF-25
0 0.00 0.00 0.00 0.00 0.00 0.00
10 67.95±0.76 68.16±0.78 62.33±0.23 60.57±0.78 65.44±0.65 73.44±0.44
20 69.58 ±0.88 66.96±0.67 64.55±0.56 62.55±0.55 68.67±0.34 75.55±0.69
30 71.45±0.98 68.55±0.45 65.32±0.76 64.77±0.65 71.89±0.15 77.21±0.99
40 74.80±0.78 69.54±0.10 67.32±0.62 65.43±0.21 73.45±0.56 78.43±0.55
50 76.42±0.34 72.65±0.51 69.23±0.66 68.36±0.44 75.83±0.67 80.12±0.77
60 79.11±0.10 75.33±0.67 71.43±0.56 69.66±0.44 78.67±0.41 82.±55±0.54
70 79.89±0.67 76.87±0.55 72.55±0.65 70.76±0.56 81.90±0.88 84.90±0.79
80 81.89±0.87 79.85±0.45 74.62±0.98 74.44±0.89 84.89±0.60 87.43±0.35
90 83.07±0.54 81.74±0.61 76.67±0.86 77.21±0.43 86.15±0.37 89.41±0.56
100 85.87±0.22 84.74±0.43 78.55±0.37 80.66±0.65 89.67±0.12 90.32±0.66
110 89.65±0.62 85.88±0.36 81.34±0.77 82.43±0.89 91.74±0.50 92.55±0.56
120 92.45±0.31 88.11±0.48 82.21±0.54 85.76±0.88 93.47±0.22 95.80±0.82
In-vitro drug release data of optimized Ondansetron Hydrochloride MDFs

0
20
40
60
80
100
120
0 2 4 6 8 10 12 14
%DrugRelease
Time (Second)
% Drug Release MDF-5 % Drug Release MDF-8
Percentage drug release profile of optimized ondansetron hydrochloride MDFs

DRUG- EXCIPIENT COMPATIBILITY STUDY
S.NO. Named group Band frequencies of Drug
(cm-1)
Band frequency of film
(Drug + excipients)
(cm-1)
1 Aromatic C― H
(Stretching)
3500 3442.18
2 C = O 1632.74 1653.23
3 C = N 1475.11 1496.17
4 C ― CL 749.24 805.95
As the peaks of film is close to the peaks of drug no interaction has been seen which
can affect the property of drug.
FT-IR spectra of the drug FT-IR spectra of the film

CONCLUSION
 MDFs is a innovative dosage form for symptoms where rapid onset of
action of drug is required and at the same time patient compliance is
improved. Solvent casting technique is a simple and reproducible, for the
preparation of MDFs of ondansetron hydrochloride. The results have
shown that, change in the concentration of the polymers has potential to
effect the disintegration time of the film and % drug content. In
combination with 1% HPMC E5, 1% HPMC E15 and 1% of PVP K30
has shown promising faster disintegration time (19.66 Second) followed
by rapid drug release within 120 sec (95.80%). The present review shows
that ondansetron HCL MDFs can be successfully prepared and it may
provide quick onset of action, enhanced patient compliance and
increased therapeutic efficacy when compared with other dosage forms.
23-Jun-20

REFERENCES
• Deepthi, R. and Kumar, S, k., “Formulation and evaluation of amlodipine besylate oral thin
films” , International Journal of Pharmaceutical Sciences & Research, 2017
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Dissolving Oral Film of Diazepam”, Journal of Pharmacovigilance, 2016
• Pathan, A., Gupta, M, K., Jain, N,K., Dubey, A. and Aggarwal, A,”Formulation and
evaluation of fast dissolving films of promethazine Hydrochloride using Different
surfactant”, 3(1) 74-84, 2016.
• Mahajan, A., ”formulation and evaluation of fast dissolving buccal films of sertraline”,
International journal of pharmaceutics and research, ISSN 0975-9244, 2012.
• Panchal, M., Patel, H., Bagada and Vadalia, R,K, ”Formulation And Evaluation of Mouth
Dissolving film Of Ropinrole Hydrochloride By using Pullan Polymer”, International
journal of pharmaceutical research and allied science, 2012.
23-Jun-20

• Bala, R., Pawar, P, Kumar, S. and Arora,S.,”Orally dissolving Strips A new approach to
oral drug delivery system”, International Journal of Pharmaceutical science and
Research, 3(2), 67-76, 2013.
• Karki, S., Kim, H, Na,J,S., Shin, D, Jo, K. and Lee, J, ”Thin films as an emerging
Platform for drug delivery”, Asian journal of pharmaceutical science, pp. 559-574,
2016.
• Mehboob, H, B, M., Riaz, T., Jamshaid, M., Bashir,I. and Zulfiqar, S,”Oral Films A
Comprehensive Review “International current pharmaceutical journal, 5(12);111-117,
2016
23-Jun-20

Formulation and evaluation of mouth dissolving film containing antiemetic drug for the treatment of motion sickness

Formulation and evaluation of mouth dissolving film containing antiemetic drug for the treatment of motion sickness

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