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Controlled Release Matrix Tablets of Olanzapine: Influence of Polymers on the In Vitro Release and Bioavailability

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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.

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Acknowledgment

We acknowledge the help of Dr. Nadeem Irfan Bukhari, Assistant Professor of Pharmaceutics for analyzing the pharmacokinetic data; the University of Peshawar for financial support, Colorcon Asia Pacific, India for generously gifting Ethocel standard 7FP premium and Methocel K100 LV-CR; Bryon Pharma, and Pakistan for the provision of some chemicals and manufacturing facilities. We are obliged to Danis Pharma, Islamabad, for gifting olanzapine powder.

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  1. Department of Pharmacy, University of Peshawar, Peshawar, 25120 N.W.F.P, Pakistan

    Amir Badshah, Fazal Subhan & Khalid Rauf

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  1. Amir Badshah
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  2. Fazal Subhan
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Correspondence to Amir Badshah.

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Badshah, A., Subhan, F. & Rauf, K. Controlled Release Matrix Tablets of Olanzapine: Influence of Polymers on the In Vitro Release and Bioavailability. AAPS PharmSciTech 11, 1397–1404 (2010). https://doi.org/10.1208/s12249-010-9510-0

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