Pharmaceutical Cocrystals—A Review

Abstract

The design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offers a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of cocrystals, cocrystal preparation and characterization, a comparison of different (traditional and novel) methods for cocrystal formation and the implications for regulatory control and intellectual property protection. Traditionally, cocrystals can be prepared by solvent evaporation method, grinding, and slurry method, but every method has its limitations for certain conditions. The current trend for cocrystal formation uses sophisticated methods such as the hot melt extrusion method, spray-drying method, supercritical fluid technology and the newest method: laser irradiation. The purpose of the development of a new method is not only to overcome the limitation of traditional cocrystallization methods, but also to generate simpler steps and a continuous process for the production of the cocrystal product. This article provides a brief explanation of each method that can be used to generate pharmaceutical cocrystals as well as evaluation of cocrystals. This article also covers how the developing field of cocrystallization may impact the pharmaceutical intellectual property landscape.

Novel Pharmaceutical Cocrystals of Gefitinib: A Credible Upswing in Strategic Research to Ameliorate Its Biopharmaceutical Challenges

“…As ΔpK a < 0 is expected to produce a cocrystal and a salt for ΔpK a ≥ 3 with a ΔpK a of 0−3 falling in region of uncertainty where either a salt or cocrystal may be formed. 16 Therefore, the ΔpK a rule suggests that GEF is likely to form a cocrystal with INCT and VAN. Additionally, these coformers also have potential synthons suitable for hydrogen bonding with alkoxy, quinazoline, morpholine, or halophenyl moieties present in the drug molecule (Figure 1).…”

Recent Progress on Synthesis, Characterization, and Performance of Energetic Cocrystals: A Review

“…Cocrystal preparation processes include solid-state grinding, solution-reaction crystallization, solvent evaporation, and slurry conversion, and have all been extensively reported to date. Numerous synthesis techniques have been utilized for the creation of pharmaceutical cocrystals [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. In addition, pharmaceutical cocrystals are easier to produce than ECCs.…”

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

“…Several different strategies have been reported by researchers for preparing cocrystals [ 30 ]. One classic technique for obtaining cocrystals is crystallization in solution.…”