Preparation and Characterization of Aripiprazole Cocrystals with Coformers of Multihydroxybenzene Compounds
- Authors
- Cho, Min-Yong; Kim, Paul; Kim, Ga-Young; Lee, Ju-Yeon; Song, Keon-Hyoung; Lee, Min-Jeong; Yoon, Woojin; Yun, Hoseop; Choi, Guang J.
- Issue Date
- Dec-2017
- Publisher
- American Chemical Society
- Keywords
- formulation
- Citation
- Crystal Growth & Design, v.17, no.12, pp 6641 - 6652
- Pages
- 12
- Journal Title
- Crystal Growth & Design
- Volume
- 17
- Number
- 12
- Start Page
- 6641
- End Page
- 6652
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7000
- DOI
- 10.1021/acs.cgd.7b01281
- ISSN
- 1528-7483
1528-7505
- Abstract
- A novel co-crystal of aripiprazole (ARI), the active substance in the atypical antipsychotic Abilify, with orcinol (ORC) as a coformer, was prepared, characterized, and compared with other ARI co-crystals with dihydroxy- and trihydroxybenzene coformers [catechol (CAT), resorcinol (RES), and phloroglucinol (PHL)] reported previously (Nanubolu, J. B.; Ravikumar, K. CrystEngComm 2016, 18, 1024-1038). Three preparation methods were used: neat grinding (NG), liquid-assisted grinding (LAG), and solvent evaporation (SE). Based on single-crystal X-ray diffraction (SC-XRD) measurements, the crystal structure of the ARI-ORC co-crystal was determined to be monoclinic. The melting point of ARI-ORC co-crystal was found to be 184-185 degrees C, higher than existing ARI co-crystals with multihydroxybenzene coformers. Additionally, the ARI ORC co-crystal showed the highest dissolution rate among those in the test group in an acetonitrile-water 10/90 cosolvent. We investigated how the co-crystallization pathway and the dissolution behavior might correlate with the coformer moiety, primarily in terms of its chemical structure and melting point. Co-crystallization between ARI and PHL via grinding (NG or LAG) required the highest activation energy, mainly due to the coformer's higher melting point. The dissolution rate of ARI co-crystals was not obviously correlated with the coformer's melting point or its molecular weight. However, the high dissolution rate of ARI ORC co-crystals was possibly associated with the bond angle of D-H center dot center dot center dot A for O3-H3O center dot center dot center dot N2 in the co-crystal's superlattice structure. The stability of ARI co-crystals was examined by aging these powders in a controlled oven at 80 degrees C/98% relative humidity for 1 week. We observed that all of the co-crystal powders, except for the aripiprazole-catechol (ARI-CAT) pair, underwent no noticeable degradation or physicochemical change upon treatment. In conclusion, we can consider the novel ARI-ORC co-crystal as a potential drug substance with the enhanced dissolution behavior in aqueous media and good stability under stressed conditions.
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