FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL FILMS OF ONDANSETRON HYDROCHLORIDE
M.Pharm Dissertation Protocol Submitted to the
Rajiv Gandhi University of Health Sciences,
Karnataka, Bangalore.
By
Mr. Manish Kumar V. Patel.(B.Pharm)
Under the esteemed guidance of
Mr. R.G. Patil. M.Pharm
Lecturer
Department of Pharmaceutics
B.L.D.E.A’s College of Pharmacy, Bijapur-586103
2012-2013
Rajiv Gandhi University of Health Sciences, Karnataka Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate andAddress
(In block letters) / MR. MANISHKUMAR V. PATEL.
SHAKTI NAGAR SOCIETY PART-2
MANSAROVAR ROAD,PALANPUR-385001
GUJARAT
2. / Name of the Institution / B.L.D.E.A’S COLLEGE OF PHARMACY,
B.L.D.E.A’S UNIVERSITY CAMPUS,
BIJAPUR-586 103
3. / Course of study and subject / M.PHARM-ODD BATCH (PHARMACEUTICS)
4. / Date of admission to Course / 13-12-2011
5. / Title of the Topic / FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL FILMS OF ONDANSETRON HYDROCHLORIDE
6. / Brief resume of the intended work :
6.1 Need for the study
6.2 Review of literature
6.3 Objectives of the study / Enclosure-I
Enclosure-II
Enclosure-III
7. / Material and Methods :
7.1 Source of data : ENCLOSURE-IV
7.2 Method of collection of data (including sampling procedure, if any)
: ENCLOSURE-IV
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
: NO
7.4 Has ethical clearance been obtained from your institution in case of 7.3
: NO
8. / List of References (about 4-6) : ENCLOSURE-V
9. / Signature of candidate
10. / Remarks of the guide / : ENCLOSURE-VI
11. / Name & Designation of
(in block letters)
11.1 Guide
11.2 Signature
11.3 Co-Guide (if any)
11.4 Signature
11.5 Head of Department
11.6 Signature / MR. R.G.PATIL.
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
B.L.D.E.A’S COLLEGE OF PHARMACY, BIJAPUR-586 103
---
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Dr. C.C.PATIL
12. / 12.1 Remarks of the chairman & principal: This study can be carried out in our
laboratory
12.2 Signature
ENCLOSURE-I
6) Brief resume of the intended work
6.1 Need for the study
Development of new drug delivery system has been one of the major thrust area of pharmaceutical research these days. Buccal cavity has a wide variety of functions and it acts as an excellent site for the absorption of drugs. Film type dosage forms can be used for transdermal and also for buccal or sublingual use.1 one of the major limitations associated with buccal route of administration is the lack of dosage form retention at the site of absorption. Consequently Bioadhesive polymers have extensively been employed in buccal drug delivery systems in the form of adhesive patches, adhesive films, adhesive tablets and buccal gels. Buccal films are highly flexible and ensure more accurate dosing of the drug compared to gels and ointments. Moreover, buccal films are suitable for protecting wound surfaces, thus reducing pain and increasing the treatment effectiveness.2
Buccal drug delivery has many advantages over conventional modes of drug administration; it avoids hepatic first pass metabolism and improves patient compliance.3
To reduce the frequency of administration and to improve patient compliance, a sustained release formulation of Ondansetron Hydrochloride is desirable.
Ondansetron is a serotonin 5HT 3 receptor antagonist is a potent antiemetic drug, which is used in control of nausea, vomiting associated with cancer chemotherapy. It exhibits only 60-70% of oral bioavailability because of first pass metabolism and has a relative short half-life of 3-5 h.
Studies have shown that Ondansetron hydrochloride is well absorbed through the buccal or sublingual mucosa.4 Dose of the drug is 0.15 mg/kg, 3 times/day beginning 30 minutes prior to chemotherapy or 0.45 mg/kg once daily or 8-10 mg 1- 2 times/day or 24 mg or 32 mg once daily.5 Ondansetron hydrochloride was selected as the model drug for the investigation because it has got certain characteristics that a drug should possess to get absorbed through buccal route viz., biphasic solubility and low molecular weight (365.9 g/mol). Moreover it undergoes first-pass metabolism so, its bioavailability may be improved when delivered through buccal route makes it a suitable candidate for administration via a buccal delivery system.6
ENCLOSURE-II
6.2. Review of literature
1.Koland M. et al ., have prepared Losartan potassium is an angiotensin II receptor antagonist with an oral bioavailability of only 33% due to extensive first pass metabolism. Mucoadhesive buccal films of Losartan potassium were prepared using hydroxypropyl methyl cellulose (HPMC) and retardant polymers ethyl cellulose (EC) or Eudragit RS 100. Ex vivo permeation studies of Losartan potassium solution through porcine buccal mucosa showed 90.2 % absorption at the end of 2 hours. In vitro drug release studies reveal that all films exhibited sustained release in the range of 90.10 to 97.40 % for a period of 6 hours.7
2. Alagusundaram M. et al., have designed oral transmucosal drug delivery bypasses liver and avoids presystemic elimination in the gastro intestinal tract and liver. The present investigation highlights the formulation and evaluation of mucoadhesive buccal films of ranitidine. The mucoadhesive buccal films of ranitidine were prepared by solvent casting technique using polymers like Hydroxy propyl methyl cellulose-15 cps and poly vinyl pyrrolidone. The formulated films were evaluated for their physiochemical parameters like surface pH, percentage moisture absorption, percentage moisture loss, swelling percentage, water vapour transmission rate, thickness, weight of the films, folding endurance and drug content. In vitro release studies were performed with pH 6.8 phosphate buffer solution. Good results were obtained both in physico chemical characteristics and in vitro studies. The formulation was found to be right and suitable candidate for the formulation of ranitidine buccal film for therapeutic use.8
3. Semalty M. et al., have prepared Mucoadhesive buccal films of Glipizide by solvent casting technique using hydroxypropylmethylcellulose, sodium carboxymethylcellulose, carbopol-934P and Eudragit RL-100. Prepared films were evaluated for weight, thickness, surface pH, swelling index, in vitro residence time, folding endurance, in vitro release, permeation studies and drug content uniformity. The films exhibited controlled release over more than 6 h. From the study it was concluded that the films containing 5 mg Glipizide in 4.9% w/v hydroxypropyl methylcellulose and 1.5% w/v sodium carboxymethylcellulose exhibited satisfactory swelling, an optimum residence time and promising drug release. The formulation was found to be suitable candidate for the development of buccal films for therapeutic use.9
4. Parmar V.J. et al., have designed formulations of Carvedilol were developed by using release rate controlling film forming polymers like Eudragit RL-100, PVP, HPMC, NaCMC and Carbopol 934 in various combinations by solvent casting technique using plasticizer propylene glycol with and without penetration enhancers like DMSO, Tween 60 and castor oil. It has a short half life of 2h and bioavailability of 25%. Therefore the present investigation is concerned with the development of the buco-mucoadhesive films, which were designed to prolong the buccal residence time, to increase penetration through buccal mucosa and thus increase the bioavailability and its half life. The most satisfactory formulation followed zero order kinetic and showed no significant changes in the physicochemical parameters, in-vitro release pattern and ex-vivo diffusion studies during stability studies for two months.10
5. Rao R.N.G. et al., have prepared buccal films of Zolmitriptan. In the present research work, buccal films were prepared using different mucoadhesive polymers by Solvent Casting Technique. The half-life of Zolmitriptan is 2.5 to 3 hrs and it undergoes hepatic metabolism, the absolute oral bioavailability is about 40 to 50%. So, in order to improve the bioavailability and efficacy, we have prepared Buccal films were characterized for number of parameters like physical appearance and surface texture, weight uniformity, thickness, folding endurance, swelling index, surface pH, drug content uniformity, in-vitro residence time, and in-vitro drug release study Release of Zolmitriptan from all films followed zero order. Hence these formulations of Zolmitriptan mucoadhesive buccal films promising one as the controlled drug delivery, shows moderate swelling, convenient resident time will lead to improve the bioavailability and greater therapeutic efficacy.11
6. Singh S. et al., have prepared and evaluate buccal Bioadhesive films of Clotrimazole for oral candidiasis with different proportions of sodium carboxymethylcellulose and carbopol 974P (CP 974P) by solvent casting method and evaluated for bioadhesion, in vitro drug release and effectiveness against Candida albicans. Films containing 5% CP 974P of the total polymer were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The microbiological studies revealed that drug released from the film could inhibit the growth of C. albicans for 6hr.12
7. Lohani A. et al., have prepared the formulation and evaluation of mucoadhesive buccal films of Ranitidine Hydrochloride by solvent casting technique using polymers like hydroxyl propyl methyl cellulose E15 (HPMC E15) and carbopol 934P alone or in combination. The formulated films were evaluated for their physiochemical parameters like surface pH, percentage moisture absorption, percentage moisture loss, swelling percentage, water vapor transmission rate, thickness, weight of the films, folding endurance and drug content. In vitro release studies were performed with pH 6.8 phosphate buffer solution. The films exhibited controlled release more than 12 h. The formulation was found to be right and suitable candidate for the formulation of ranitidine buccal film for therapeutic use.13
ENCLOSURE-III
6.3. Objectives of the study
The present work is planned with the following objectives
Ø Preparation of standard calibration curve of Ondansetron hydrochloride
Ø Development of mucoadhesive buccal Films using polymers like carbopol 934p, Eudragit RL 100, hydroxyethyl cellulose, sodium alginate, HPMC, PVP, methyl cellulose, sodium alginate etc.
Ø To perform evaluation parameters like
1. Surface pH study
2. Content uniformity
3. Folding endurance
4. Swelling percentage study
5. Determination of in vitro residence time
6. Measurement of mucoadhesive strength
7. In vitro release study
8. Stability Studies for selected formulation will be carried out using stability chambers as per ICH guidelines.
9. Prepared buccal films will be subjected to compatibility studies using FT-IR and DSC instruments.
ENCLOSURE-IV
7) MATERIALS AND METHODS
7.1. Source of data
The data will be collected by performing various laboratory experiments, referring journals, text books and other literature.
7.2. Method of collection of data
The whole data is planned to collect from laboratory experiments which includes the following:
1) Preparation of standard calibration curve of Ondansetron hydrochloride
2) Evaluation parameters such as, Surface pH study, content uniformity, folding endurance, swelling percentage study, determination of in vitro residence time, measurement of mucoadhesive strength, in vitro release study, stability studies, compatibility studies.
ENCLOSURE-V
8) List of Reference:
1. S Raghuraman., G. Velrajan., R Ravi. B Jeyabalan., Johnson D.B., V Sankar. 2002 “Design and Evaluation of Propranolol Hydrochloride Buccal Films”. Ind. J. Pharm. Sci. 64, 1: 32-36.
2. Yehia S.A., El-Gazayerly O.N., Basalious E.B. 2OO9 “Fluconazole Mucoadhesive Buccal Films: In Vitro/In Vivo Performance”. Curr Drug Dev. 6: 17-27
3. Nagaich U., Chaudhary V., Sharma P., Yadav A. 2009 “Formulation and Development of Metoprolol tartrate Bucco-Adhesive Films”. Pharm. Res. 01.
4. Koland M., Sandeep V.P., Charyulu N.R. 2010 “Fast dissolving sublingual films of Ondansetron hydrochloride: Effect of additives on in vitro drug release
And mucosal permeation”. Pharm. 2, 3: 216-222.
5. Mehta K.K., Patel N.K., Ganatra M.H., Patel T.D., Dr. Patel N.J. “Formulation and Process Optimization Of Gastro-Retentive Floating Tablet Of Ondansetron Hcl”. J. P. R. H. C. 2, 3: 253-357.
6. Dharani S., Shayeda. 2010 “Formulation And In-Vitro Evaluation of Mucoadhesive Buccal Patch of Ondansetron Hcl”. Int. J. Pharm. Sci. Nano Tech. 3, 1.
7. Koland M., Charyulu R.N., Parch P. 2010 “Mucoadhesive films of Losartan Potassium for Buccal delivery: Design and Characterization”. Ind. J. Pharm. Educ. Res. 44, 4.
8. Alagusundaram M., Chengaiah B., Ramkanth S., Parameswari S.A., Chetty C.M.S., Dhachinamoorthi D. 2009 “Formulation and Evaluation of Mucoadhesive Buccal Films of Ranitidine”. Int. J. Pharm. Tech. Res. 1, 3: 557-563.
9. Semalty M., Semalty A., Kumar G. 2008 “Formulation and Characterization of Mucoadhesive Buccal Films of Glipizide”. Ind. J. Pharm. Sci. 70, 1: 43–48.
10. Parmar V.J., Lumbhani A. N., P Vijayalakshmi., Jha S. 2010 “ Formulation development and Evaluation of Buccal Films of Carvedilol”. Int. J. Pharm. Sci. Res. 1, 8.
11. Rao N.G.R., Munde M.R., Hadi M.A., Ghurghure S.M. 2011 “Design and Development of Mucoadhesive Drug Delivery System of Zolmitriptan”. Int. J.
Pharm. Tech. 3, 1: 1658-1673.
12. Singh S., Jain S., Muthu M.S., Tiwari S., Tilak R. 2008 “Preparation and Evaluation of Buccal Bioadhesive Films Containing Clotrimazole”. AAPS. Pharm. Sci. Tech. 9, 2.
13. Lohani A., Prasad N., Arya R.K. 2011 “Formulation and characterization of mucoadhesive buccal films of ranitidine hydrochloride”. Int. J. Pharm. Sci. Res. 2, 9: 2457-2462.
ENCLOSURE-VI
10) Remarks of the Guide
The present work is aimed to develop mucoadhesive buccal Films of Ondansetron hydrochloride. The drug has a shorter biological half-life of about 3-5 hours and it undergoes first pass metabolism. Therefore, it needs to be administered frequently in order to achieve constant plasma levels, but the frequent administration may leads to dose accumulation and toxicity. Hence, to conquer this limitation, development of sustained release system for Ondansetron hydrochloride is necessary.
The proposed study can be carried out in the laboratory.
Mr. R.G. Patil M.Pharm
Lecturer
Research Guide
9