Co-crystal: A pharmaceutical technique to improve physical characteristics of Active Pharmaceutical Ingredient

Abstract

Co-crystal is defined as a material which contains two or more discrete molecular entities in the crystal structure. Co-crystals of many compounds are known for years in solid state chemistry. However, it is only recently that pharmaceutical cocrystals have generated much commercial and academic interest. Pharmaceutical cocrystals are important because they can improve many properties of the parent API like solubility, dissolution rate, stability, crystallinity and many more (Almarsson and Zaworotko, 2004). Biopharmaceutics Classification System (BCS) of drugs classifies drugs into four major categories based on their solubility and permeability behavior. BCS Class II and Class IV drugs suffer from poor aqueous solubility. Poor aqueous solubility of hydrophobic drugs can result in poor absorption, low bioavailability and poses challenges for drug development process (Desiraju, 2003a). Enhancing bioavailability of poorly water-soluble BCS class II and BCS class IV drugs therefore becomes necessary to improve drug's efficacy. Co-crystallization enhances solubility of BCS class II and class IV drug. In addition to BCS of drugs, Developability Classification System (DCS) of drugs also plays a significant role in determining the development of pharmaceutical formulations, especially the oral formulations based on its solubility in biorelevant media such as FaSSIF (Fast State Simulated Intestinal Fluid) and FeSSIF (Fed State Simulated Intestinal Fluid) rather than its solubility in buffers (Dunitz, 2003b; Jain and Patel, 2015; Vadher et al., 2009). Very few reports are available in the literature where researchers have determined the dissolution rate of cocrystals of poorly water-soluble drugs in biorelevant media. The studies illustrate that cocrystals exhibited enhanced dissolution rate in biorelevant media and buffer as well indicating that the DCS serves as a highly relevant tool in determining develop ability of cocrystals of poorly water-soluble APIs. Enhancing aqueous solubility of poorly water-soluble drugs without compromising on stability is one of the major challenges faced by the pharmaceutical industries during drug discovery and development processes (Steed, 2013). Crystal Engineering is a tool which can be used to tailor the physicochemical properties of Active Pharmaceutical Ingredients (APIs) such as melting point, dissolution rate, aqueous solubility, refractive index, surface activity, habit, density, electrostatic, mechanical and optical properties. Cocrystallization is one of Co-crystal: A pharmaceutical technique to improve physical characteristics of Active Pharmaceutical Ingredient Reetu Yadav *, Ashutosh Kumar Yadav , Anita Singh 1 1 2