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Impact of Formulation Parameters on In Vitro Release from Long-Acting Injectable Suspensions

Abstract

The development of long-acting injectable (LAI) suspension products has increased in recent years. A better understanding of the relationship between the physicochemical properties of these products and their in vitro as well as in vivo performance is expected to further facilitate their development and regulatory review. Using Depo-SubQ Provera 104® as the reference listed drug (RLD), four qualitatively and quantitatively (Q1/Q2) equivalent LAI suspensions with different formulation properties were prepared. Two recrystallization methods (solvent evaporation and antisolvent) were utilized to obtain active pharmaceutical ingredient (API) with different properties and solid-state characterization was performed. In addition, two different sources of the major excipient were used to prepare the Q1/Q2 equivalent suspensions. Physiochemical characterization and in vitro release testing of the prepared Q1/Q2 equivalent suspension formulations and the RLD were conducted. In vitro drug release was dependent not only on the particle size, the morphology, and the crystallinity of the API but also on the residual solvent in the API. The excipient source also affected the drug release rates.

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Abbreviations

LAI:

Long-acting injectable

MPA:

Medroxyprogesterone acetate

PLGA:

Poly(lactic-co-glycolic acid)

API:

Active pharmaceutical ingredient

Q1/Q2 equivalent:

Qualitatively and quantitatively equivalent

HIV:

Human immunodeficiency virus

IM:

Intramuscular

SC:

Subcutaneous

RLD:

Reference listed drug

PEG:

Polyethylene glycol

PVP:

Polyvinylpyrrolidone

PXRD:

Powder X-ray diffraction

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Acknowledgments

The authors are grateful to Xiaoyu (James) Lu (Undergraduate Research Assistant, School of Pharmacy, University of Connecticut) for technical assistance.

Funding

Funding for this project was made possible by a Food and Drug Administration grant (HHSF223201710135C).

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Correspondence to Diane J. Burgess.

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The views expressed in this paper do not reflect the official policies of the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

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Guest Editors: Diane Burgess, Marilyn Morris and Meena Subramanyam

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Bao, Q., Zou, Y., Wang, Y. et al. Impact of Formulation Parameters on In Vitro Release from Long-Acting Injectable Suspensions. AAPS J 23, 42 (2021). https://doi.org/10.1208/s12248-021-00566-0

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KEY WORDS

  • medroxyprogesterone acetate
  • long-acting injectable
  • suspensions
  • Depo-SubQ Provera 104®
  • drug release