Ranolazine Co-Crystal: Molecular Docking, Coformer Selection, In vitro, In vivo Pharmacokinetic Assesment in Rat...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Materials Science

Background:

• Ranolazine, an antianginal agent, suffers from poor water solubility and bioavailability.
• These limitations restrict its clinical efficacy and therapeutic applications.

Purpose of the Study:

• To enhance the solubility and bioavailability of Ranolazine.
• To investigate the potential of co-crystal formation for improving Ranolazine's physicochemical properties.

Main Methods:

• In silico screening was employed to identify suitable co-formers (2-amino caffeine, nicotinamide, benzamide).
• Co-crystals were synthesized using solvent drop grinding, antisolvent addition, and slow evaporation techniques.
• Characterization involved UV, FTIR, DSC, in vitro dissolution, and pharmacokinetic studies in rats using RP-HPLC.

Main Results:

• Co-crystal formation successfully improved Ranolazine's dissolution rate.
• Pharmacokinetic studies demonstrated enhanced Ranolazine plasma concentrations (Cmax) and bioavailability.
• The developed RP-HPLC method was validated for accuracy, sensitivity, linearity, and specificity.

Conclusions:

• In silico screening is effective for selecting co-formers to improve drug physicochemical properties.
• Ranolazine co-crystals show promise for enhanced therapeutic outcomes and improved drug performance.
• Further preclinical and clinical studies are warranted to validate Ranolazine co-crystals for therapeutic use.