title: Morphological and Crystalline Transitions in Monohydrous and Anhydrous Aripiprazole for a Long-Acting Injectable Suspension.
abstract: Many formulation and manufacturing processes can lead to morphological and crystalline transitions in many polycrystalline drugs, changing the properties of active pharmaceutical ingredients (APIs) such as solubility and physical stability which influence their therapeutic effects and safety and so limit their usefulness. Here, we report significant changes in crystal forms and morphology, including the shape and size of particles during the manufacture of off-white aripiprazole (APZ) dry powders used for long-acting and injectable suspensions. With the optimal top-down approach, powders were prepared by recrystallizing uniform monohydrous APZ (MA) and polycrystalline anhydrous APZ (AA) form III, characterized by thermal analysis, PXRD, and FT-IR. However, powders involving MA (MAP) with a lower mean size (2.126 μm), narrower distribution (span = 1.90), and higher stability compared with AA dry powders (AAP) were found to exhibit dehydration behavior and morphological changes after completion of the preparation processes based on the results of thermal analysis. In the case of APZ powders, we wished to obtain more information to guide in the industrial production and experimental design of suspensions in the future.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Luying
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Jing
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang, China. tanglab@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000068180:Aripiprazole / Q000008:administration & dosage* / Q000737:chemistry; D003460:Crystallization; D007267:Injections; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013535:Suspensions
chemical_list: D011208:Powders; D013535:Suspensions; D000068180:Aripiprazole
keywords: crystal growth; dehydration behavior; depot; lyophilized suspensions; polymorphism 