This document presents a study on the development and characterization of orodispersible films containing ondansetron using the polymer pullulan. The objectives were to formulate ondansetron orodispersible films using solvent casting, characterize the films, and evaluate their drug release properties. Various films were formulated using different polymer concentrations. The optimized formulations were evaluated for characteristics like disintegration time, thickness, drug content, and in vitro drug release. The optimized films showed disintegration within 10-12 seconds and released over 90% of the drug within 120 seconds.

1. 1
Presented by:
Neha Benedicta Fernandes
7th Semester
B.Pharm
DEVELOPMENT AND CHARACTERIZATION
OF
ONDANSETRON MOUTH DISPERSIBLE FILMS
USING PULLULAN POLYMER

2. CONTENTS
 INTRODUCTION
 IDEAL CHARACTERISTICS OF ODF’S
 ONDANSETRON HYDROCHLORIDE (DRUG)
 ADVANTAGES AND DISADVANTAGES OF ODF’s
 MECHANISM OF ODF’s
 NEED FOR THE STUDY
 AIMS AND OBJECTIVES
 MATERIALS AND METHOD
 EVALUATION OF OPTIMIZED FORMULATION
 RESULTS
 REFERENCE

3.  A fast dissolving oral film is a solid dosage form which when placed in the oral cavity ,
immediately hydrates by soaking saliva following disintegration or dissolution releasing
the API within a few seconds (5-30 sec) from the dosage form.
 First developed in 1970’s as an alternate to tablets and capsules.
 Hydrophilic polymers- Enables rapid dissolution on contact with saliva.
 Upon disintegration in mouth the drug achieves improved clinical effect through pre-
gastric absorption from mouth, pharynx and oesophagus as saliva passes down into the
stomach.
 Higher bioavailability than conventional tablet dosage forms.
 More flexibilty and comfort than adhesive tablets.
 Oral gels easily washed off and separated from mucosa
INTRODUCTION

4. An ideal ODF should
 Be thin and flexible
 Be stable to guarantee a robust manufacturing and packaging process
 Have ease of handling and administration
 be transportable, not tacky and keep a plane form without rolling up
 provide an acceptable taste
 Give a pleasant mouth-feel
 Have disintegration time as short as possible
IDEAL CHARACTERISTICS OF ODF’s

5. 5
• Selective serotonin 5-HT3 receptor antagonist.
• Blocks the action of serotonin, a natural substance responsible for emesis
• Prevents nausea and vomiting caused by cancer chemotherapy, radiation therapy and
surgery
• Also used for morning sickness and hyperemesis gravidarum in pregnancy.
ONDANSETRON HYDROCHLORIDE (DRUG)

6. 6
ADVANTAGES

7. 7
MECHANISM
Oral thin
film
Place it on
the tongue
Upon wetting
by saliva
disintegrates
into small
particles
The API is then
absorbed
through the
mouth, pharynx
and oesophagus
Quick onset of
action- enhanced
bioavailability

8. 8
NEED FOR THE STUDY
 Conventional oral dosage forms of ondansetron.HCI at a specific dose
take about 30-45 min to cause anti –emetic effect which isn’t desirable.
 In case of Ondancetron.HCI orodispersible films, disintegration and
dissolution of dosage form occurs rapidly (within few seconds) providing
rapid onset of action with minimal dose.
 Hence improves patient compliance.

9. 9
 To develop orodispersible films of ondansetron.HCI by solvent casting
technique by using pullulan and HPMC polymer combinations and to evaluate
the same in vitro.
Specific Objectives of the study:
1. To perform the pre-formulation study of the drug to verify the
compatibility of drug and polymers.
2. To formulate the orodispersible films of ondansetron.HCI.
3. To characterize the prepared films of ondansetron.HCI
4. To optimize the various formulations using Design Expert Software.
5. To evaluate the in vitro release characteristics of orodispersible films
using simulated salivary fluid.
AIMS AND OBJECTIVES

10. 10
MATERIALS AND METHOD
Materials
 Ondansetron HCl (drug)
 Pullulan(polymer)
 HPMC E15 (polymer)
 Polyethylene glycol (PEG) –(plasticizer))
Formulation
i. Preparation of casting solution
The casting solution was prepared using the polymers pullulan and HPMC E15 in
combination. The weighed quantity of drug (8.75 mg), and polymers (50-150 mg) were
dissolved in 5 ml of water. Aspartame (40 mg) was dissolved in 3 ml of ethanol in a
beaker. Both the solutions were mixed and stirred on magnetic stirrer until dissolved.
PEG was added as a plasticizer (0.1-0.3 ml). The beaker was covered with an aluminium
foil, and allowed to stand overnight to remove air bubbles.
ii. Preparation of orodispersible films (SOLVENT CASTING METHOD)
The casting solution (8 ml) was poured into petri plate (70 cm2) and kept aside to allow
for controlled evaporation of the solvent. The dried film was removed by peeling and cut
into squares with a dimension of 2 × 2 cm (4 cm2), each film contained 4mg drug and
kept in a desiccator over fused calcium carbonate for 2 days for further drying and
SOLVENT CASTING

11. 11
EVALUATION OF OPTIMIZED ONDANSETRON ORODISPERSIBLE FILMS
1) Disintegration time
The in-vitro disintegration time was determined by petri dish method. Briefly, 2 ml
simulated saliva (pH 6.8) was placed in a clean dry petri dish and the film (2 X 2 cm) was
placed on its surface. The time required for the complete disintegration of the film was
noted as the disintegration time. The test was performed on three strips of each
formulation batch and mean ± SD was calculated.
2) Uniformity of weight
The weight of the optimised films (2 X 2 cm) was determined using a digital analytical
balance. The weight was taken in triplicates and the mean ± SD was calculated.
3) Uniformity of film thickness
The Film thickness of optimized formulations was determined using the micrometre screw
gauge. The film (2 X 2 cm) was placed between the jaws of the screw gauge movable by
the thimble. The thimble consists of an auxiliary scale which was divided into 50 equal
divisions. Main scale was a millimetre scale graduated to 0.5 mm. The film was held by
ratchet. Thickness of the film was measured at 5 different positions (central and four
corners) for each of the formulations and the mean thickness ± SD was computed.
4) Folding endurance
The folding endurance of the optimized films was determined by repeatedly folding a
small strip of film (2 X 2 cm) in the centre, between fingers and the thumb and then
opened. This

12. as termed as one folding. The process was repeated till the film showed breakage or
cracks in the centre of the film. The folding endurance is given by the number of times
the film could be folded at the same place without breaking gave the value . The
experiment was done in triplicates and the mean ± SD was calculated.
5) Surface pH
The optimized film to be tested was placed in a petri dish and was moistened with 0.5 ml
of distilled water and kept for 30 sec. The electrode of the pH meter was placed in
contact with the surface of the formulation and allowed to attain equilibrium for 1 min.
The experiment was done in triplicates and the mean ± SD was calculated.
6) Tensile strength
Tensile strength and percentage elongation of the optimized films was determined by
using universal strength testing machine (F. 4026, Instron Ltd., Japan) with a 5 kg load
cell. It consists of two load cell grips, the lower one is fixed and upper one is movable.
The test film of specific size (4×1 cm) was fixed between these cell grips and force was
gradually applied till the film breaks. The tensile strength of the film was taken directly
from the dial reading in kilograms/cm2 and the percentage elongation was determined by
calculating the difference between initial and final length (while breaking) of the film.
The force and elongation were measured when the film broke. The standard deviation of
tensile strength and percentage elongation was computed from their mean value.
7) Percentage moisture loss
The percentage moisture loss was measured to check integrity of the optimized films at

13. % Moisture loss=
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡−𝐹𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
× 100
8) Drug content uniformity
The optimized film of specific area (2 X 2 cm) was cut and transferred to a graduated
flask containing 100 ml of simulated salivary fluid pH 6.8 and stirred on a magnetic
stirrer for 4 h. The solution was then filtered using a Whaman® filter paper. The filtered
solution was diluted using the simulated salivary fluid. The absorbance will be measured
using UV spectrophotometer (V-630, JASCO, Japan) at λ max 210 nm.
9) In vitro drug release
The optimized films of known weight and dimension (2 X 2 cm) were placed in a beaker
containing 20 ml of simulated salivary fluid (pH 6.8) as the dissolution medium
maintained at 37 ± 0.5°C. The medium was stirred at 100 rpm. Aliquots (5 ml) of samples
were taken at 5 sec time intervals, and the same volume of fresh phosphate buffer was
replaced. Samples were filtered, diluted suitably and analyzed using UV/Visible
spectrophotometer (V-630, JASCO, Japan) at λ max 210 nm. The cumulative percentage
drug release was calculated and plotted against time (sec).
dry conditions. Optimized films were weighed and kept in a desiccator containing
anhydrous calcium chloride. After three days, films were taken out and reweighed.The
standard deviation of percentage moisture loss was computed from their mean value.

14. 14
RESULTS
1) Disintegration time:
The disintegration time for the optimized ondansetron hydrochloride films F1, F2 and F3
was found to be 9 ± 1 s, 12 ± 1 s and 10 ± 1 s respectively which is within 30 sec.
2) Uniformity of Weight:
The weight of F1, F2 and F3 films was found to be ~33.43 mg, ~42.61 mg and ~38.34 mg
respectively.
3) Uniformity of film thickness:
The values were almost uniform in F1, F2 and F3 formulations and it was found to be 0.21
± 0.02, 0.23± 0.01 and 0.26 ± 0.06 respectively.
4) Folding Endurance
The folding endurance was found to be 230±5, 237±7 and 241±3 for F1, F2 and F3
formulations respectively indicating good properties of elasticity and that the films can
withstand sufficient folding, while retaining its original size and shape when left aside
without any deformation.
5) Surface pH
The surface pH of optimized formulations F1, F2 and F3 was found to be 7.0 ± 0.1 to 7.1 ±
0.1 and 7.0 ± 0.1 respectively which is close to neutral pH, and can be concluded that they
may have less potential to irritate the oral cavity, thereby they are comfortable to
administer as orodispersible films.

15. 15
6) Tensile strength
The tensile strength of the F1, F2 and F3 formulations was found to be 1.42 ± 0.3, 1.53 ±
0.3 and 1.57 ± 0.4 kg/cm2 respectively and the percentage elongation was found to be
21.60 ± 0.4 %, 25.33 ± 0.2 % and 24.21 ± 0.3 % respectively.
7) Percentage Moisture Loss
By taking the initial weight of the films and the weight after keeping for three days in the
desiccator, the percentage moisture loss was calculated for F1, F2 and F3 formulations and
it was found to be 7.4 ± 0.32, 8.2 ± 1.10 and 9.8 ± 0.56 % respectively
8) Drug Content Uniformity
F1, F2 and F3 formulations content uniformity was found to be 93.26 ± 0.68, 90.44 ± 0.21
and 87.13 ± 0.65 % respectively
9) In-vitro drug release
The optimized formulations F1, F2 and F2 showed the cumulative drug release ~98.37 %,
~93.45 and ~94.55 % respectively at the end of 120 sec.

16. REFERENCE
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10.1208/s12249-012-9839-7.
• Reddy PC, Chaitanya KSC, Rao YM. A review on bio adhesive buccal drug delivery
systems: current status of formulation and evaluation methods. Daru. 2011;19(6):385-
403.
• Morales JO, McConville JT. Manufacture and characterization of mucoadhesive
buccal films. European J Pharm Biopharm. 2011;77(2):187-99.
doi:10.1016/j.ejpb.2010.11.023.
• Clissold SP, Heel RC. Transdermal hyoscine (Scopolamine). A preliminary review of its
pharmacodynamics properties and therapeutic efficacy. Drugs. 1985;29(3):189-207.