EFFECT OF DIFFERENT GRADES OF HPMC AND EUDRAGIT ON DRUG RELEASE PROFILE OF DOXOFYLLINE SUSTAINED RELEASE MATRIX TABLETS AND IVIVC STUDIES

Abstract

Present studies aimed for design of sustained release matrix tablets of Doxofylline through in vitro as well as pharmacokinetic studies that will reduce the frequency of dosing and improve patient compliance and to establish in vitro-in vivo correlation. Wet granulation methods were adopted using different grade of release retarding polymers HPMC and Eudragit in various proportion to optimise the release profile. Different precompression and post compression characterization of tablet was carried out and the results satisfied according to the pharmacopoeia specifications. In-vitro release studies were carried out in USP II paddle type dissolution apparatus for different formulations and the dissolution profiles of all the formulations were compared with standard marketed formulation by calculating the similarity factor (f2) and difference factor (f1). The formulation DSRF11 containing both the grades of HPMC (i.e HPMC K4M and HPMC K15M) having 7% each and 8% of Eudragit RSPO was considered as optimised formulation as the initial release was 18% and maximum release (99.19%) upto 12 h and showed highest f2 value (96.41) and lowest f1 value (0.88) was considered as optimised formulation. The hardness, friability, drug content and swelling index of DSRF11 found as 5.17+/-0.8 kg/cm2, 0.62+/-0.04, 102.35+/-1.44 and 96.29+/-2.16 respectively. The kinetic of in-vitro drug release profile of DSRF11 followed zero order kinetic model due to highest regression value (R2=0.993) having drug release mechanism as anomalous diffusion coupled with erosion (n=0.732). FTIR and DSC analysis revealed that there was no interaction between the drug and the polymers, thus these polymers can be conveniently used in development of Doxofylline sustained release matrix tablets. Accelerated stability studies of optimized formulation (DSRF11) showed a little change in physicochemical properties as well as drug release profiles at the end of 90 day indicating the stability of formulations. In vivo pharmacokinetic studies of optimised formulation and marketed standard formulation were carried out in New Zealand white rabbit and in vitro-in vivo correlation was established. Thus the current study clearly indicate a promising potential of the Doxofylline sustained release matrix tablets system as an alternative to the conventional dosage form as it control in vitro burst effect of the highly water-soluble drug, Doxofylline hydrochloride and can prevent in-vivo dose dumping.