Implications of Drug-Polymer Interactions on Time-Temperature-Transformation: A Tool to Assess the Crystallization Propensity in Amorphous Solid Dispersions

Rahul Lalge; N. S.Krishna Kumar; Raj Suryanarayanan

doi:10.1021/acs.molpharmaceut.2c01004

Implications of Drug-Polymer Interactions on Time-Temperature-Transformation: A Tool to Assess the Crystallization Propensity in Amorphous Solid Dispersions

Rahul Lalge, N. S.Krishna Kumar, Raj Suryanarayanan

Pharmaceutics

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4 Scopus citations

Abstract

The critical cooling rate (CR_crit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (t_C) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CR_crit for the dispersions prepared with each polymer. The observed differences in CR_crit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer t_C and decreased CR_crit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CR_crit of amorphous NIF was ∼17.5 °C/min. Addition of 20% w/w polymer resulted in a CR_crit of ∼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.

Original language	English (US)
Pages (from-to)	1806-1817
Number of pages	12
Journal	Molecular pharmaceutics
Volume	20
Issue number	3
DOIs	https://doi.org/10.1021/acs.molpharmaceut.2c01004
State	Published - Mar 6 2023

Bibliographical note

Funding Information:
The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network ( www.mrfn.org ). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline.

Funding Information:
The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network (www.mrfn.org). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline.

Publisher Copyright:
© 2023 American Chemical Society.

Keywords

amorphous solid dispersion
crystallization
drug−polymer interactions
hot-melt extrusion
hydroxypropylmethyl cellulose acetate succinate (HPMCAS)
nifedipine
polyvinylpyrrolidone (PVP)
time−temperature−transformation

PubMed: MeSH publication types

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

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10.1021/acs.molpharmaceut.2c01004

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@article{59e81d98e00e44f0b8c567bbf9d4f25d,

title = "Implications of Drug-Polymer Interactions on Time-Temperature-Transformation: A Tool to Assess the Crystallization Propensity in Amorphous Solid Dispersions",

abstract = "The critical cooling rate (CRcrit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (tC) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CRcrit for the dispersions prepared with each polymer. The observed differences in CRcrit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer tC and decreased CRcrit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CRcrit of amorphous NIF was ∼17.5 °C/min. Addition of 20% w/w polymer resulted in a CRcrit of ∼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.",

keywords = "amorphous solid dispersion, crystallization, drug−polymer interactions, hot-melt extrusion, hydroxypropylmethyl cellulose acetate succinate (HPMCAS), nifedipine, polyvinylpyrrolidone (PVP), time−temperature−transformation",

author = "Rahul Lalge and Kumar, {N. S.Krishna} and Raj Suryanarayanan",

note = "Funding Information: The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network ( www.mrfn.org ). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline. Funding Information: The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network (www.mrfn.org). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline. Publisher Copyright: {\textcopyright} 2023 American Chemical Society.",

year = "2023",

month = mar,

day = "6",

doi = "10.1021/acs.molpharmaceut.2c01004",

language = "English (US)",

volume = "20",

pages = "1806--1817",

journal = "Molecular pharmaceutics",

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AU - Lalge, Rahul

AU - Kumar, N. S.Krishna

AU - Suryanarayanan, Raj

N1 - Funding Information: The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network ( www.mrfn.org ). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline. Funding Information: The project was partially supported by the William and Mildred Peters endowment fund (1701-11392-20662-UMF0003766-2108004). Parts of this work were carried out at the Characterization Facility, University of Minnesota, a member of the National Science Foundation-funded Materials Research Facilities Network (www.mrfn.org). This work used resources of the Advanced Photon Source; a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract no. DEAC02-06CH11357. We thank Dr. Andrey Yakovenko and Dr. Wenqian Xu for their help with the use of the 17BM beamline. Publisher Copyright: © 2023 American Chemical Society.

PY - 2023/3/6

Y1 - 2023/3/6

N2 - The critical cooling rate (CRcrit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (tC) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CRcrit for the dispersions prepared with each polymer. The observed differences in CRcrit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer tC and decreased CRcrit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CRcrit of amorphous NIF was ∼17.5 °C/min. Addition of 20% w/w polymer resulted in a CRcrit of ∼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.

AB - The critical cooling rate (CRcrit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (tC) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CRcrit for the dispersions prepared with each polymer. The observed differences in CRcrit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer tC and decreased CRcrit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CRcrit of amorphous NIF was ∼17.5 °C/min. Addition of 20% w/w polymer resulted in a CRcrit of ∼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.

KW - amorphous solid dispersion

KW - crystallization

KW - drug−polymer interactions

KW - hot-melt extrusion

KW - hydroxypropylmethyl cellulose acetate succinate (HPMCAS)

KW - nifedipine

KW - polyvinylpyrrolidone (PVP)

KW - time−temperature−transformation

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M3 - Article

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AN - SCOPUS:85147868635

SN - 1543-8384

VL - 20

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JO - Molecular pharmaceutics

JF - Molecular pharmaceutics

IS - 3

ER -

Implications of Drug-Polymer Interactions on Time-Temperature-Transformation: A Tool to Assess the Crystallization Propensity in Amorphous Solid Dispersions

Abstract

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