title: Development of controlled-release matrix tablet of risperidone: influence of Methocel®- and Ethocel®-based novel polymeric blend on in vitro drug release and bioavailability.
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 Methocel® K100 LV-CR and Ethocel® standard 7FP premium, were slugged. Each batch of granules (250-1,000 μm), 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% Methocel® and 60% Ethocel® (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 Ethocel®, while the gel layer formed of Methocel® 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 ± 2°C/75 ± 5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit's serum, were analyzed with HPLC-UV at λ(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.
authors.affiliation: Department of Pharmacy, University of Peshawar, Khyber Pakhtoonkhwa, Pakistan. amir_badshah@upesh.edu.pk
authors.forename: Amir
authors.initials: A
authors.lastname: Badshah
authors.forename: Fazal
authors.initials: F
authors.lastname: Subhan
authors.forename: Khalid
authors.initials: K
authors.lastname: Rauf
authors.forename: Nadeem Irfan
authors.initials: NI
authors.lastname: Bukhari
authors.forename: Kifayatullah
authors.initials: K
authors.lastname: Shah
authors.forename: Samiullah
authors.initials: S
authors.lastname: Khan
authors.forename: Zia
authors.initials: Z
authors.lastname: Ahmed
authors.forename: Ihsanullah
authors.initials: I
authors.lastname: Khan
mesh_terms: D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000592:standards; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D003692:Delayed-Action Preparations / Q000592:standards; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D008297:Male; D008747:Methylcellulose / Q000737:chemistry / Q000493:pharmacokinetics* / Q000592:standards; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000592:standards; D011817:Rabbits; D018967:Risperidone / Q000737:chemistry / Q000493:pharmacokinetics* / Q000592:standards; D013608:Tablets, Enteric-Coated
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D013608:Tablets, Enteric-Coated; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D018967:Risperidone