In vitro and in vivo evaluation of Quetiapine fumarate controlled gastroretentive floating drug delivery system

A Kishore babu, MV Ramana

Abstract


The aim of the present work was to develop and optimize gastroretentive floating system of Quetiapine fumarate (QF) for the effective treatment of Schizophrenia. The present study was carried out with an objective of preparation and in vivo evaluation of floating tablets of using QF as a model drug using HPMC polymers, Gelucire 43/01 and Polyox WSR 301 to improve oral bioavailability of QF floating tablets by increasing gastric residence time. The tablets were prepared by direct compression method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15M and Polyox WSR 301. The optimized formulation (F12) containing HPMC K15M and Polyox WSR301 showed 98.6% drug release at the end of 12h. Changing the viscosity grade of HPMC from K15M to K100M had no significant effect on drug release profile. The optimized formulations (F12) containing sodium bicarbonate 40mg per tablet showed desired buoyancy (floating lag time of about 32seconds and total floating time of >12h). Optimized formulation (F12) followed diffusion controlled zero order kinetics and non-fickian transport of the drug. FTIR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. The best formulation (F12) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 6h in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs. Studies to evaluate the pharmacokinetics in vivo showed better bioavailability, area under the concentration–time curve, elimination rate constant and half-life than marketed product.


Keywords


Quetiapine fumarate, Floating drug delivery system, HPMC, Polyox WSR 301, Radiographic studies.

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