A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

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

doi:10.1016/j.xphs.2022.08.028

A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	204-212
Number of pages	9
Journal	Journal of Pharmaceutical Sciences
Volume	112
Issue number	1
DOIs	https://doi.org/10.1016/j.xphs.2022.08.028
State	Published - Jan 2023

Bibliographical note

Funding Information:
S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC ( DMR-2011401 ) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged.

Funding Information:
S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC (DMR-2011401) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged.

Publisher Copyright:
© 2022 American Pharmacists Association

Keywords

Amorphous solid dispersion (ASD)
Crystallization
Miscibility
Overlap concentration (c*)
Physical stability
Viscosity

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10.1016/j.xphs.2022.08.028

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title = "A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions",

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",

author = "Sichen Song and Chenguang Wang and Bo Zhang and Lodge, {Timothy P.} and Sun, {Changquan Calvin} and Siegel, {Ronald A.}",

note = "Funding Information: S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC ( DMR-2011401 ) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged. Funding Information: S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC (DMR-2011401) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged. Publisher Copyright: {\textcopyright} 2022 American Pharmacists Association",

year = "2023",

month = jan,

doi = "10.1016/j.xphs.2022.08.028",

language = "English (US)",

volume = "112",

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AU - Wang, Chenguang

AU - Zhang, Bo

AU - Lodge, Timothy P.

AU - Sun, Changquan Calvin

AU - Siegel, Ronald A.

N1 - Funding Information: S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC ( DMR-2011401 ) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged. Funding Information: S.S. thanks Prof. Masao Doi (Wenzhou Institute, UCAS) for delightful communication on c* and Dr. David Giles (Polymer Characterization Facility, UMN) for helpful discussion of viscosity measurement. Parts of this work were carried out in the Polymer Characterization Facility and the Characterization Facility, UMN, which receives partial support from the NSF through the MRSEC (DMR-2011401) and the NNCI (ECCS-2025124) programs. Funding from Industrial Partners for Research in Interfacial and Materials Engineering (IPRIME, UMN) is also acknowledged. Publisher Copyright: © 2022 American Pharmacists Association

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N2 - 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.

AB - 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.

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KW - Miscibility

KW - Overlap concentration (c)

KW - Physical stability

KW - Viscosity

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ER -

A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

Abstract

Bibliographical note

Keywords

MRSEC Support

PubMed: MeSH publication types

Publisher link

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University of Minnesota Materials Research Science and Engineering Center (DMR-2011401)

IRG-2: Mesoscale Network Materials

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A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

Abstract

Bibliographical note

Keywords

MRSEC Support

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Projects

University of Minnesota Materials Research Science and Engineering Center (DMR-2011401)

IRG-2: Mesoscale Network Materials

Cite this