A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

Sichen Song; Chenguang Wang; Bo Zhang; Changquan Calvin Sun; Timothy P Lodge; Ronald A Siegel

doi:10.1016/j.xphs.2022.08.028

A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

J Pharm Sci. 2023 Jan;112(1):204-212. doi: 10.1016/j.xphs.2022.08.028. Epub 2022 Aug 26.

Authors

Sichen Song¹, Chenguang Wang², Bo Zhang³, Changquan Calvin Sun², Timothy P Lodge⁴, Ronald A Siegel⁵

Affiliations

¹ Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, United States; School of Mathematics, University of Minnesota, Minneapolis, MN 55455, United States.
² Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, United States.
³ Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, United States.
⁴ Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, United States; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, United States.
⁵ Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, United States; Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: siege017@umn.edu.

PMID: 36030843
DOI: 10.1016/j.xphs.2022.08.028

Abstract

Miscibility is an important indicator of physical stability against crystallization of amorphous solid dispersions (ASDs). Currently available methods for miscibility determination have both theoretical and practical limitations. Here we report a method of miscibility determination based on the overlap concentration, c*, which can be conveniently determined from the viscosity-composition diagram. The determined c* values for ASDs of two model drugs, celecoxib and loratadine, with four different grades of polyvinylpyrrolidone (PVP), were correlated strongly with the physical stability of ASDs. This result suggests potential application of the c* concept in guiding the design of stable high drug loaded ASD formulations. A procedure is provided to facilitate broader adoption of this methodology. The procedure is easy to apply and widely applicable for thermally stable binary drug/polymer combinations.

Keywords: Amorphous solid dispersion (ASD); Crystallization; Miscibility; Overlap concentration (c*); Physical stability; Viscosity.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Celecoxib / chemistry
Crystallization
Drug Compounding / methods
Drug Stability
Povidone* / chemistry
Solubility

Substances

Povidone
Celecoxib