Modified Formulation of Febuxostat: Improved Efficacy and Safety

Objective: Febuxostat, a xanthine oxidoreductase inhibitor, is a drug of choice for hyperuricemia and Gout. But it also suffers from drawbacks in terms of pharmacokinetic profile and toxicity. It is available as immediate release formulation in the market. The objective is to develop a modified release formulation of febuxostat that can serve the dual purpose of increasing the efficacy and decreasing the toxicity, thereby improving safety. Methods: Pharmacokinetic and pharmacodynamic data, including drug concentration profile, efficacy data and toxicity data have been reviewed thoroughly. Based on available data, target pharmacokinetic profile has been identified as about 50 % reduction in Cmax Results: Based on dissolution data and Wagner-Nelson calculations, the plasma concentration profile has been predicted for the developed formulation. It reconfirms that developed formulation will achieve the desired objectives. Formulation stability has been established up to 6 months under accelerated conditions. and improvement in plasma drug concentration above required level during 6-24 hour. Desired in-vitro dissolution profile has been selected, and formulation modification has been sought to achieve the desired profile. The formulation has been prepared with a partial dose in the form of immediate release (IR) and remaining dose as an extended release (ER). IR and ER formulations have been developed separately and combined to form Inlay tablets containing ER inner tablet surrounded by IR. Conclusion: The developed formulation is a potential candidate for filing to a regulatory agency with the advantage of higher efficacy and less toxicity, which will be beneficial to the patient population and has good commercial viability.