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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.

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Acknowledgments

This research was supported by a grant from the National Science Foundation for Fostering Talents in Basic Research of China (Grant No. J1103606).

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Correspondence to Xing Tang.

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Xinyi Tan and Yue Zhong contributed equally to this work.

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Tan, X., Zhong, Y., He, L. et al. Morphological and Crystalline Transitions in Monohydrous and Anhydrous Aripiprazole for a Long-Acting Injectable Suspension. AAPS PharmSciTech 18, 1270–1276 (2017). https://doi.org/10.1208/s12249-016-0592-1

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  • DOI: https://doi.org/10.1208/s12249-016-0592-1

KEY WORDS

  • crystal growth
  • dehydration behavior
  • depot
  • lyophilized suspensions
  • polymorphism