Development of Controlled-Release Matrix Tablet of Risperidone: Influence of MethocelA®- and EthocelA®-Based Novel Polymeric Blend on In Vitro Drug Release and Bioavailability

Controlled-release (CR) matrix tablet of 4 mg risperidone was developed using flow bound dry granulation-slugging method to improve its safety profile and compliance. Model formulations F1, F2, and F3, consisting of distinct blends of MethocelA (R) K100 LV-CR and EthocelA (R) standard 7FP premium, were slugged. Each batch of granules (250-1,000 mu m), obtained by crushing the slugs, was divided into three portions after lubrication and then compressed to 9-, 12-, and 15-kg hard tablets. In vitro drug release studies were carried out in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using a paddle dissolution apparatus run at 50 rpm. The CR test tablet, containing 30% MethocelA (R) and 60% EthocelA (R) (F3) with 12-kg hardness, exhibited pH-independent zero-order release kinetics for 24 h. The drug release rate was inversely proportional to the content of EthocelA (R), while the gel layer formed of MethocelA (R) helped in maintaining the integrity of the matrix. Changes in the hardness of tablet did not affect the release kinetics. The tablets were reproducible and stable for 6 months at 40 A +/- 2A degrees C/75 A +/- 5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit's serum, were analyzed with HPLC-UV at lambda (max) 280 nm. The CR test tablet exhibited bioequivalence to reference conventional tablet in addition to the significantly (p < 0.05) optimized peak concentration, C (max), and extended peak time, T (max), of the active moiety. There was a good association between drug absorption in vivo and drug release in vitro (R (2) = 0.7293). The successfully developed CR test tablet may be used for better therapeutic outcomes of risperidone.