Morphological and Crystalline Transitions in Monohydrous and Anhydrous Aripiprazole for a Long-Acting Injectable Suspension
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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.
KEY WORDScrystal growth dehydration behavior depot lyophilized suspensions polymorphism
This research was supported by a grant from the National Science Foundation for Fostering Talents in Basic Research of China (Grant No. J1103606).
- 2.Chue P, Chue J. A review of aripiprazole long-acting injection. Current medical research and opinion. 2015;1–12.Google Scholar
- 4.Cresswell P, Paquette SM, Hickey M, Perkin K, Smith G, Liversidge E, et al. ARIPIPRAZOLE PRODRUG COMPOSITIONS. US Patent. 2016; 20,160,045,495.Google Scholar
- 5.Citrome L. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil. Expert review of clinical pharmacology. 2015;1–18.Google Scholar
- 6.Kostanski JW, Matsuda T, Nerurkar M, Naringrekar VH. Controlled release sterile injectable aripiprazole formulation and method. Google Patents. 2015.Google Scholar
- 13.Hartman P. Crystal growth: an introduction: North Holland. 1973.Google Scholar
- 15.Griesser U, Hilfiker R. Polymorphism in the Pharmaceutical Industry. ed Rolf Hilfiker, Wiley-VCH Verlag GmbH & Co. 2006; 211–33.Google Scholar
- 17.Florey K. Profiles of drug substances, excipients and related methodology. New York: Academic; 1983.Google Scholar