Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Abstract

The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.

Differences in Coformer Interactions of the 2,4-Diaminopyrimidines Pyrimethamine and Trimethoprim

“…By controlling the crystal packing, cocrystals with the desired properties can be designed. The largest and most widely studied class of cocrystals are pharmaceutical cocrystals, that is, two drugs or one drug and a pharmaceutically acceptable coformer held together in the same crystal lattice by noncovalent interactions. − Cocrystallization allows for the manipulation and optimization of the physicochemical properties of an active pharmaceutical ingredient (API) such as chemical and physical stability, hygroscopicity, solubility, and dissolution behavior without the need for chemically modifying the API molecule. APIs often have more than one functional group that can interact with coformers.…”

Nano- and Crystal Engineering Approaches in the Development of Therapeutic Agents for Neoplastic Diseases

“…Similarly, Entresto ® (Otsuka Pharmaceutical Co., Ltd., Japan), a medication used in the treatment of heart failure, is a combination of valsartan, an angiotensin II inhibitor, and sacubitril, a neprilysin inhibitor. The resultant co-crystal has led to an increased bioavailability of valsartan [56]. In the treatment of bacterial infections, the co-crystal formed by co-crystallizing amoxicillin and clavulanate exhibited increased antibacterial activity when compared to amoxicillin alone, due to β-lactamase inhibition attributed to clavulanate [22] Similarly, co-crystallization of isoniazid and pyrazinamide resulted in synergistic effect for tuberculosis treatment [57].…”

Simultaneous Improvement of Dissolution Behavior and Oral Bioavailability of Antifungal Miconazole via Cocrystal and Salt Formation

“…A great number of techniques are known today for obtaining multicomponent crystals [ 23 ]. However, researchers rarely investigate the effect of different preparation methods of multicomponent crystals on the API’s physicochemical properties and pharmacokinetics [ 24 , 25 ].…”

“…However, researchers rarely investigate the effect of different preparation methods of multicomponent crystals on the API’s physicochemical properties and pharmacokinetics [ 24 , 25 ]. Researchers typically use one of the most common methods for preparing multicomponent crystals, such as grinding, while the preparation method has a great influence on the characteristics of the solid state of a chemical (crystallinity, porosity, particle size, surface area) and its physicochemical properties, respectively [ 23 ]. In this work, the MCL multicomponent solid forms were obtained via multiple methods (liquid-assisted grinding (LAG), slurrying and lyophilization) and characterized comprehensively.…”