Pharmaceutical Co-Crystals: An Emerging Approach for Enhancement of Solubility and Bioavailability of a Drug

Co-crystallization is an emerging approach for enhancing physicochemical properties like solubility, stability, bioavailability of poorly soluble drugs of BCS class II in pharmaceutical development without changing the chemical composition and considered better alternatives to optimize drug properties. Co-crystal is a crystalline entity consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former formed by intermolecular interactions like Hydrogen bonding, π-π stacking and Van der Waals forces. In this article, an overview of pharmaceutical cocrystals will be presented along with the intermolecular interactions (Chemistry of Co-crystals), methods of their preparations, characterization of co-crystals altered physicochemical properties. Furthermore, this article also gives a brief explanation about newer trends in co-crystals with application of co-crystals in medicines and industries. *Corresponding Author Email: shaktipalpatil@yahoo.com Received 04 April 2019, Accepted 16 April 2019 Journal home page: http://www.ajptr.com/ Patil et. al., Am. J. PharmTech Res. 2019;9(05) ISSN: 2249-3387 www.ajptr.com 2 INTRODUCTION The pharmaceutical industry encompasses wide variety of products out of which most are manufactured as solid dosage forms. Successful pharmaceutical development of a drug molecule depends not only on its potency and selectivity but also on its stability. Thus, the properties active pharmaceutical ingredients (APIs) depends on the identity of its constituents as well as on their arrangements. Many potential drugs failed due their unfavourable properties such as poor water solubility, unfavourable bioavailability, physical and chemical instability, inappropriate dissolution. It is easy to solve solubility problem of amorphous form, but difficult for crystalline drug. The precise control of molecular orientation and packing arrangement in the crystal of drug molecules can improve their solubility with no alteration in stability and biological activity. The solid APIs exist in different forms such as crystalline solids, amorphous forms, polymorphs, solvates, hydrates, salts. Many a times an API cannot be formulated in its pure form due to various issues of instability, solubility, compatibility, dissolution, etc. Thus, they are converted to solid forms such as polymorphs, salts, solvates, hydrates, amorphous and co-crystals. Improving the solubility of BCS class II drugs is currently one of the main challenges for the pharmaceutical industry for drug development. The traditional approaches for enhancing poor aqueous solubility (e.g., salt formation, micronization, solid dispersion formulations) often fail to produce a viable solid form, as the increase in dissolution rate achieved is frequently insufficient to provide adequate enhancement of bioavailability. Over the last decade, there has been growing interests in the design of pharmaceutical co-crystals, which emerges as a potential method for enhancing the bioavailability of drugs with low aqueous solubility. What are co-crystals? The crystalline materials possess different physical properties from their molecular arrangements within their solid forms. When these arrangements or the interactions within the solids are altered, it results in the formation of new crystals having altered physical or chemical properties. These are commonly called as mixed crystals or crystal that contains two or more molecules. Co-crystals are made up of various reactants which are solids at room temperature. These are formed by noncovalent interactions between solid molecules such as hydrogen bonding, Van der Waal forces and π-π interactions. Solvates or hydrates contains solid and liquid components into them where as cocrystals have only solid components presents into them at room temperature. Hence, a co-crystal can be defined as “a multicomponent crystal that is formed between two compounds that are solids Patil et. al., Am. J. PharmTech Res. 2019; 9(05) ISSN: 2249-3387 3 www.ajptr.com under ambient conditions”. The co-crystal approach has valuable advantages for pharmaceutical companies in terms of opportunities for intellectual property protection and the possibility of extending the life cycles of established APIs. How are co-crystals different from solvates and hydrates? Co-crystals are often confused with pseudopolymorphs like solvates and hydrates. Co-crystals differ from solvates and hydrates in physical state of components present into them. Solvates and hydrates are crystalline forms of solid drugs belongs to multi-component systems. The multicomponents systems are either comprised two or more solids or one or more solids and liquid. Solvate is a crystal form with either stoichiometric or non-stoichiometric amount of solvent and hydrate is a solvate with water as the solvent. A co-crystal is also a multicomponent system, but that is formed between two compounds and both are in solid state under ambient conditions. Figure 1: Solvate Hydrate and Co-crystal Co-crystals versus salts Sometimes co-crystals and salts may be confused. The understanding of fundamental difference between salts and co-crystals is very important for both preformulation studies and chemical/pharmaceutical development aspects. Salts and co-crystals can be considered as opposite ends of multi-component structures. Salts formation is a three-component system having an acid, base and one or more solvents involving acid-base reaction between the API and an acidic or basic substance. Co-crystals are used as an alternative to salts when these cannot be formed because of the absence of ionisable sites in the API. Co-crystals are formed using a drug, a co-crystallizing agent and an appropriate solvent.