Effect of cocrystallization in augmentation of in vitro and in vivo performance of irbesartan

Abstract

Pharmaceutical co-crystals are a promising approach for fine-tuning the physicochemical properties of active pharmaceutical ingredients (APIs) like solubility and dissolution. The current study describes generation of irbesartan cocrystal with succinic acid, its characterization and bioavailability assessment. Irbesartan (poorly water- soluble drug) is used in treatment of diseases like hypertension, heart failure, myocardial infarction and diabetic nephropathy. It is a fluffy material, with relatively low bulk and tap density. Irbesartan has certain undesirable flow characteristics, for example, is sticky and can adhere to surfaces such as tablet punch faces and dies, causing problems in tableting, Hence, cocrystal was prepared to enhance solubility, dissolution, bioavailability and to improve its micromeritic properties. Solvent drop grinding method was used to formulate irbesartan-succinic acid cocrystal. Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and Powder X-Ray Diffraction (PXRD) were used to identify the emergence of a new crystalline phase. Saturation solubility studies were conducted in 0.1NHCl solution. The pharmacokinetic behavior of irbesartan and its cocrystal was investigated in male Albino rats. The significant improvement in solubility and dissolution rate was observed in the case of cocrystals than pure irbesartan. The AUC0-24 hr of the cocrystal and Cmax was found to be 1.65-fold and 1.56-fold increase respectively in terms of bioavailability as compared to the pure drug. Hence Cocrystal approach can be successfully used for solid state manipulation for the possible improved bioavailability of BCS class II drugs – irbesartan.

Keywords

• Irbesartan
• cocrystals
• succinic acid
• dissolution rate
• bioavailability

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