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 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.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.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.Â

Improvement of physicochemical parameters of acyclovir using cocrystallization approach

Acyclovir is an antiviral drug having potent activity against the virus of herpes family and varicella zoster. Unfortunately, drug suffers very poor oral bioavailability (15-30%). The main objective of present study was to develop acyclovir cocrystals with improved solubility which may result in improvement of bioavailability. Hansen solubility approach was used as a tool to predict the cocrystal formation of a drug with selected coformer. Cocrystals of acyclovir with various coformers were screened in order to enhance their water solubility. Cocrystals of the drug were prepared using various methods like solvent evaporation, wet grinding, and antisolvent addition. Formation of cocrystals by solvent evaporation method was found to be better method amongst all. Optimization of cocrystal formation was carried out by employing different solvents as well as the stoichiometric ratio of acyclovir with that of coformer. Synthesis of cocrystals was optimized using water as a solvent system resulted in good agreements. The potential cocrystal formation of acyclovir was characterized by IR, PXRD and DSC techniques. An in-vitro dissolution study was performed to determine the dissolution rate of cocrystals. The results suggest that acyclovir forms cocrystals with tartaric acid and the initial dissolution rate of synthesized cocrystals were considerably faster as compared to pure acyclovir

Improvement of physicochemical parameters of acyclovir using cocrystallization approach

ABSTRACT Acyclovir is an antiviral drug having potent activity against the virus of herpes family and varicella zoster. Unfortunately, drug suffers very poor oral bioavailability (15-30%). The main objective of present study was to develop acyclovir cocrystals with improved solubility which may result in improvement of bioavailability. Hansen solubility approach was used as a tool to predict the cocrystal formation of a drug with selected coformer. Cocrystals of acyclovir with various coformers were screened in order to enhance their water solubility. Cocrystals of the drug were prepared using various methods like solvent evaporation, wet grinding, and antisolvent addition. Formation of cocrystals by solvent evaporation method was found to be better method amongst all. Optimization of cocrystal formation was carried out by employing different solvents as well as the stoichiometric ratio of acyclovir with that of coformer. Synthesis of cocrystals was optimized using water as a solvent system resulted in good agreements. The potential cocrystal formation of acyclovir was characterized by IR, PXRD and DSC techniques. An in-vitro dissolution study was performed to determine the dissolution rate of cocrystals. The results suggest that acyclovir forms cocrystals with tartaric acid and the initial dissolution rate of synthesized cocrystals were considerably faster as compared to pure acyclovir