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Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective

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Abstract

In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug’s performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies.

Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

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Authors and Affiliations

  1. Research and Development, Neofluidics LLC, 6650 Lusk Blvd, Suite B102, San Diego, California, 92121, USA

    Deepak Solomon, Nilesh Gupta & Yadir A. Guerrero

  2. Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Drake University, 2507 University Ave, Des Moines, Iowa, 50311, USA

    Nihal S. Mulla

  3. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, 8000 Utopia Parkway, St. Albert Hall, B14, Queens, New York, 11439, USA

    Snehal Shukla & Vivek Gupta

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Solomon, D., Gupta, N., Mulla, N.S. et al. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective. AAPS J 19, 1669–1681 (2017). https://doi.org/10.1208/s12248-017-0142-0

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