IN VITRO/EX VIVO EVALUATION OF NOVEL MUCOADHESIVE BUCCAL POLYMERIC FILM FOR RELEASE OF CHLORHEXIDINE

Introduction - Buccal drug delivery has recently become an important route of drug administration. Various bioadhesive mucosal dosage forms have been developed, which included adhesive tablets, gels, patches, and more recently, films. The use of polymeric films for buccal delivery has not yet been widely investigated, although they have been extensively employed in pharmaceutical tablet coating formulations to protect tablet cores from environmental extremes, improve appearance, mask undesirable taste and control the drug release. Buccal film may be preferred over adhesive tablet in terms of flexibility and comfort. In addition, they can circumvent the relatively short residence time of oral gels on the mucosa, which is easily washed away and removed by saliva . Moreover, the buccal film is able to protect the wound surface, thus reducing pain and treat oral diseases more effectively to prevent discomfort. The objective of the present study was to develop a new buccal polymeric film mucoadhesive for release controlled of Chlorhexidine as a valid adjunct in the treatment of oral Recurrent Aphtous Stomatitis (RAS). MATERIALS AND METHODS Materials - Chlorhexidine Base (Sigma Chemical, Italy); Hydroxy Propyl Methyl Cellulose grades Italy) (HPMC; Methocel® K4M, E50P and E4M); Sodium Carboxy Methyl Cellulose (Polichimica, Bologna, Italy); PolyEthylenGlycol 400 (Sigma Chemical) was used as plasticizer. All solvents (Ethanol, Carlo Erba, Italy; Buffer solution pH 7.4) used were of analytical grade. Table I shows the theoretical compositions (% w/w) of the four formulations obtained. Preparation of Polymeric Film - Four different film formulations mono-layered containing 5 mg of chlorhexidine base were produced by a casting-solvent evaporation technique that allows obtaining very thin films, transparent and mucoadhesive, starting from a soft mucilage. Drug loading - Two mg of the drug was dissolved in 20 ml ethanol: a sample of film was soaked into this solution and then dried: residual solvent was removed under high vacuum for 24 h. The drug loading was determined spectrophotometrically. Table 2 shows some parameter of the film thus obtained. Measurement of adhesive force - The test is based on the calculation of energy required to detach the dosage form from the substrate material (usually excised buccal mucosa) attached through the bioadhesive material. A tensile tester (Rheometric Scientific Inc, UK) was used to measure the adhesive force of the film (1cm×1cm; thickness: 0.8mm)with a plastic (PVC) plate. Determination of Film Thickness - The thickness measurement of transversal cuts of the film (3 cm) was performed at different points of each sample using a light microscope Standard Universal Carl Zeiss(Berlin, Germany) equipped with a micrometric ocular. Determination of swelling - Dry films (1 cm×2 cm; thickness, 1.1 mm) were incubated in phosphate buffered saline (0.1M, pH 7.4) at 37°C. At predetermined time intervals, hydrated samples were weighed after blotting the surface water with a filter paper. In vitro drug release - Drug release from the films was measured spectrophotometrically using a dissolution test apparatus. The dissolution medium was USP phosphate buffer pH 7.0, 1,000 mL (sink conditions) at 37±0.1°C, and at a stirring rate of 100 rpm. Microbiology Test - Patchs were utilized for to determinate the minimum inhibitory concentration in Petri’s Disc containing bacterial colture of Escherichia. Coli and Streptococcus Aureus. RESULTS AND DISCUSSION - An ideal buccal film should be flexible, elastic, soft, yet adequately strong to withstand breakage due to stress from mouth activities. Moreover, it must also possess good bioadhesive strength so that it can be retained in the mouth for a desired duration. Swelling of film, if exists should not be too extensive The objective of the present study was to develop a new buccal polymeric film mucoadhesive for release controlled of Chlorh...