A Practical Solid Form Screen Approach To Identify a Pharmaceutical Glutaric Acid Cocrystal for Development

Abstract

Pharmaceutical cocrystals could be used to improve the physicochemical properties of active pharmaceutical ingredients. Here, a practical solid form screen approach to identify pharmaceutical cocrystals in the early development stage is proposed. This approach first used a cogrinding screen to identify potential cocrystal former leads that could form cocrystals with the compound of interest, followed by a solvent-based screen to identify, evaluate, and generate the cocrystal candidates. This approach not only allows fast identification of the cocrystal candidates but also provides insights on their scalability. Using this approach for the development drug candidate, a glutaric acid cocrystal was identified that provided an improved intrinsic dissolution rate in comparison to that of the free form, and therefore this cocrystal is potentially a better solid form for development. The effects of solvents and structures of cocrystal formers on the cocrystal formation and the rationales for this approach are also discussed.

Use of Glutaric Acid to Improve the Solubility and Dissolution Profile of Glipizide Through Pharmaceutical Cocrystallization

“…F7 prepared by slurry method was selected as optimum formulation owing to higher drug release (12.0-93.5%) among all the formulations at pH 6.8. However, the order of in vitro release was: F7 > F8 F6 > F5 > GPZ > The results were supported by various previously reported studies (31,34). Comparative percent drug release from GPZ-GLU (1 : 1) and GPZ-GLU (1 : 2) cocrystals have shown in Figure 8 (A) and (B) respectively.…”

Cocrystals of Fenamic Acids with Nicotinamide

“…As part of the screening methodology, the fenamic acids and nicotinamide were suspended or dissolved in an organic solvent in which the solubility of both components was roughly equal, as this is more likely to produce a congruently saturating system (Table S1, Supporting Information). This strategy has been reported to maximize the chance of cocrystal precipitation 25 and indeed, using ethanol as a solvent, was successful in the isolation of the 1:1 cocrystals 1·6 and 2·6. However, the 1:2 cocrystals 3·6 and 4·6 were always observed with residual acid and/or nicotinamide present, even when a wide variety of alternative solvents and 1-10 equivalents of nicotinamide were used.…”

Imatinib mesylate cocrystals: synthesis, screening, and preliminary characterization

“…It was observed that the rate of cocrystal formation did not depend on the polymorphic form of API used [13]. Recent publications contain some interesting examples of pharmaceutical cocrystals and of practical screening for their design, synthesis, and characterization [10, 14,15].…”