Fabrication and Optimization of Novel Lornoxicam Matrix Tablets Using 3-Factor 3-Level Box-Behnken Statistical Design: Invitro and Invivo Evaluation.

ABSTRACT

In the present study efforts have been made to prepare sustained release matrix tablets of Lornoxicam. Matrix tablets were prepared by direct compression method by using Hydroxypropyl methyl cellulose K15 (HPMC- K15), Ethyl cellulose (EC) and Sodium carboxy methyl cellulose (Na-CMC) as polymers in different concentrations. A 3-factor 3- level Box-Behnken statistical design was used as an optimization tool having total of 17 experimental runs with 5 central points. All three polymers were selected as independent variables while %age drug release at various time intervals and hardness were used as dependant variables. In vivo studies were conducted on human plasma using Tenoxicam as internal standered. All the detections were made on SYKNM HPLC. Foriour Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetery (DSC) studies were conducted and no chemical interaction was found between drug and polymers. The drug release mechanism was mainly governed by non-fickian (anomalous) diffusion and zero-order (case II) transport diffusion. Regression analysis was performed on dissolution data obtained with the selected response variables and polynomial models were constructed. Polynomial models were further validated using one way ANOVA and results indicated that all the polymers used have significant effect on selected response (p>0.05). Contour plots and three dimensional response surface curves were drawn. In- vivo studies were conducted on two tablet formulation indicating slow and sustained release of the drug from matrix. From Behnken design it is possible to successfully formulate and optimize Lornoxicam sustained release matrix tablets with three polymers (HPMC- K15, EC and Na-CMC) in combination.