Formulation, Characterization and in-vitro Testing of Mucoadhesive Films of Fluoxetine Hydrochloride.

Abstract

INTRODUCTION Recent research in the area of drug delivery has been focused on design and development of innovative and more effective drug delivery systems with enhanced safety, efficacy and patient compliance. Buccal drug delivery has emerged as one of the alternative platforms for drug delivery both locally and systemically. With a relatively large surface area, relative permeability and ease of access, the buccal mucosa offers ideal location for buccal drug delivery. Major depressive disorder affects a significant portion of the world’s population. Treatment of depression takes a long period of time and some patient have difficulty in following through treatment. There is a need to develop buccal films as an alternative drug delivery system to the oral route for antidepressants in order to improve patient compliance, bioavailability, ease of administration and faster onset of action. Fluoxetine is a selective serotonin reuptake inhibitor and exerts its action by inhibiting serotonin transporter receptor. The present work provides insight into formulation of mucoadhesive buccal films containing fluoxetine hydrochloride. Pre-formulation, characterization of prepared films and in-vitro release studies were also performed. METHODOLOGY Preparation of fluoxetine mucoadhesive films was done by factorial experimental design. Pre-formulation studies were carried out to determine appropriate solvent system for use in formulation and as well as to ensure no incompatibilities between the drug and the polymers in use. Hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) in different concentrations were used as mucoadhesive polymer in the fabrication of the films. Polypropylene glycol was used as a plasticizer. The films were prepared by solvent casting technique using ethanol/dichloromethane mixture in the ratio of 1:1 as solvent system. The films obtained were analyzed for their organoleptic properties as well as physical properties including film weight, film thickness, pH, swelling index, folding endurance, uniformity of drug content and in-vitro release studies. The in-vitro release data was fitted into various kinetic models by using DD solver excel add in program to obtain the release pattern of the drug. RESULTS Pre-formulation studies revealed that ethanol/dichloromethane (1:1) was the best solvent for both drug and polymers. No incompatibilities were detected between the drug and polymers after studies using FTIR spectrophotometer. Fluoxetine buccal films were fabricated by using solvent casting technique. The prepared films were evaluated for organoleptic properties. Only formulations F1, F4, F7, F8 and F9 exhibited smooth properly and non-sticky films and were therefore considered for physical characterization. The selected formulations exhibited good physical characteristics including consistency in weight, thickness, folding endurance and pH. The swelling index ranged from 2.69 to 5.7 for the selected formulations. F1 had the lowest average drug content at 84% while F9 had the highest at 117.9%. F1 had the least cumulative drug release after 3hrs of in-vitro release studies. All the other selected formulations had release percentages between 89.9% and 93.3%. The release data of the selected formulations were subjected to various mathematical models to understand the release pattern with the value of the coefficient of regression (R2) suggesting the best fit kinetic model. The best fit kinetic model for the formulations was found to be Korsmeyers-Peppas. Formulations F1, F4 and F7 had release exponents values below 4.5 indicating that the drug transport mechanism was mainly Fickian diffusion. Formulations F8 and F9 had the value of

n at above 0.45 thus indicating drug transportation mechanism in this films to be mainly anomalous transport i.e. drug release is governed by both diffusion and erosion of polymer. CONCLUSION In the embodied work, buccal films containing fluoxetine were prepared by factorial design. HPMC and PVP were demonstrated to have good film forming and swelling properties for use in formulation of buccal films. Formulation F8 can be optimized to produce controlled release of the drug beyond 3hrs.The concentration of plasticizer used in the formulations was found to be optimum at 2-3% producing elegant non-sticky films. In summary, HPMC and PVP are potentially useful polymers for preparing mucoadhesive films of fluoxetine for buccal drug delivery system