Abstract. 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 MethocelĀ® K100 LV-CR and EthocelĀ® standard 7FP premium, were slugged. Each batch of granules (250-1,000 Ī¼m), 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% MethocelĀ® and 60% EthocelĀ® (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 EthocelĀ®, while the gel layer formed of MethocelĀ® 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 40Ā±2Ā°C/75Ā±5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit's serum, were analyzed with HPLC-UV at Ī» 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.