title: Controlled release matrix tablets of olanzapine: influence of polymers on the in vitro release and bioavailability.
abstract: Controlled-release (CR) tablet formulation of olanzapine was developed using a binary mixture of Methocel® K100 LV-CR and Ethocel® standard 7FP premium by the dry granulation slugging method. Drug release kinetics of CR tablet formulations F1, F2, and F3, each one suitably compressed for 9-, 12-, and 15-kg hardness, were determined in a dissolution media of 0.1 N HCl (pH 1.5) and phosphate buffer (pH 6.8) using type II dissolution apparatus with paddles run at 50 rpm. Ethocel® was found to be distinctly controlling drug release, whereas the hardness of tablets and pH of the dissolution media did not significantly affect release kinetics. The CR test tablets containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness exhibited pH-independent zero-order release kinetics for 24 h. In vivo performance of the CR test tablet and conventional reference tablet were determined in rabbit serum using high-performance liquid chromatography coupled with electrochemical detector. Bioavailability parameters including C(max), T(max), and AUC(0-48 h) of both tablets were compared. The CR test tablets produced optimized C(max) and extended T(max) (P < 0.05). A good correlation of drug absorption in vivo and drug release in vitro (R(2) = 0.9082) was observed. Relative bioavailability of the test tablet was calculated as 94%. The manufacturing process employed was reproducible and the CR test tablets were stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. It was concluded that the CR test tablet formulation successfully developed may improve tolerability and patient adherence by reducing adverse effects.
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120 N.W.F.P, 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
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004058:Diffusion; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D008297:Male; D008747:Methylcellulose / Q000737:chemistry*; D000077152:Olanzapine; D011817:Rabbits; D013607:Tablets / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D013607:Tablets; D001569:Benzodiazepines; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D000077152:Olanzapine
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