Optimization and Analysis of Xanthan Gum and Hypromellose Combined Matrices for Extended Release of Ranolazine Using Quality by Design

Background: Xanthan gum (XG) is a natural polymer with numerous uses. But its poor tableting and release charact1eristics reduce its usage as a tablet matrix former. Hence, the aim of the study is to improve the quality of XG by blending it with a successful semisynthetic polymer, hypromellose (HPMC). Methods: Extended release (ER) tablets were made using wet granulation technique using XG and HPMC blend. The blend was optimised using Central composite design. Prepared tablets were evaluated for in vitro tableting characteristics and drug release. In vivo absorption studies are carried out in New Zealand white rabbits. Results: Under optimal conditions, the ideal combination of factors was observed in the range of X1 : 2.75-4.25 %w/w and X2 : 10-20% w/w. At these finest concentrations, the predictable responses, the drug release at 4th hr was 36.31-40.34%, 20th hr was 82.21-91.43% and the hardness of the tablet was 6.6-8.5 kg/Cm2. The drug release of the optimized batch (RANERT 14) showed 90.9% similarity with the standard commercial ER tablets. Further, in vivo pharmacokinetic testing of the same batch showed, bioavailability (88.0 ±2.5%), mean residence time (16.1± 2.85 h) and biological half-life (11.47 ±0.42 h) against pure drug (BA: 65.0 4%; MRT: 5.1± 2.85 h; t1/2: 2.6151 ± 0.54 h). Conclusion: Comparable drug release profiles with the commercial tablets and enhanced pharmacokinetic profile made this combination as successful in achieving extended-release for a period of 24 hr by overcoming the drawbacks associated with XG.