Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

Abstract

Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH) were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration.

Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP), hydroxypropylmethyl cellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC) in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients.

Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics.

Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K₀ zero order release = 4.11 mg/h, MDT = 5.66 h) and adhesive properties and did not show any interaction between polymers and drug based on DCS scanning. This buccoadhesive system may be useful for buccal administration of VPH.