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

Abstract

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.

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

“…Additionally, the insoluble particles of Ethocel® entangled in the gel layer of Methocel® were perhaps performing the role of barrier to drug release. This idea is in line with some previously published studies (25,37). (38), tablets of high quality (optimum friability and desired hardness level) were produced.…”

“…The aforementioned objectionable point is qualified by some earlier investigations where 89.5% of fine particle ethyl cellulose (23) and 90% Methocel-and Ethocel-based blends (25) were used to extend the drug release period up to 24 h. The need for so much higher concentrations of the polymeric blend in the present study may be due to the low-viscosity gel former Methocel®,K100 LV-CR (44), leading to rapid disentanglement and erosion of the matrices.…”

“…(38), tablets of high quality (optimum friability and desired hardness level) were produced. As zero-order drug release supplies a constant amount of drug for absorption and maintains a constant level of plasma concentration (39), many researchers have sought to formulate matrices for zero-order release pattern, but few have been successful (24,25).…”

“…Blending of HPMC with other polymers (e.g., ethyl cellulose) has been recommended for the alteration of its functionalities (24). Blends of HPMC with FPEC have shown promising results in our previously published investigation (25).…”

Formulation Andcharacterization of Olanzepineloaded Mucoadhesive Microspheres

“…Moreover, it is easy for administration, no patient compliances, and flexibility in the formulation. Mucoadhesive microspheres have advantages such as efficient absorption, enhanced bioavailability of the drugs, maximum utilization of drugs, much more intimate contact with intestinal cells, better patience compliance, and targeting to specific absorption site [1][2][3].…”