Optimization of Hydroxy Propyl Methyl Cellulose and Carbomer in Diltiazem Hydrochloride Mucoadhesive Buccal Film

Abstract

Diltiazem hydrochloride (HCl) is a drug with low bioavailability due to the high rate of the first-pass metabolism and a short half-life of the drug (3-5h); hence, mucoadhesive buccal films were made to overcome this weakness. The bioavailability of Diltiazem HCl may increase if the buccal preparations can make good contact with the mucosa for a sufficient amount of time. Therefore, in this study, two polymers, Hydroxy Propyl Methyl Cellulose (HPMC) and Carbomer were combined to obtain good film characteristics, especially in residence time and mucoadhesive strength. This study aimed to optimize the amount of HPMC and Carbomer needed and evaluate the release kinetics of Diltiazem HCl from the mucoadhesive buccal film. The formula was prepared by the solvent casting method and optimized with the design expert software, while the release kinetics and mechanism were evaluated using the DDSolver program. The optimum amount of polymer obtained from optimization was 40mg of HPMC and 10mg of Carbomer. The FTIR spectra showed there was no interaction between Diltiazem HCl and other excipients. The dissolution model of Diltiazem HCl from buccal mucoadhesive film follows Korsmeyer-Peppas. The release exponent (n) of 0.55 shows a non-fickian/anomalous diffusion release mechanism. These mechanisms represent drug release controlled by a combination of diffusion and erosion. This study concluded that the buccal film was successfully formulated by using a combination of HPMC and Carbomer with the potential to increase Diltiazem HCl bioavailability and half-life by increasing its contact time and controlling the release