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Simultaneous XRD-DSC identifies correct drug-polymer solubility and miscibility for enantiotropic solid forms.

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Bibliographic Details
Title: Simultaneous XRD-DSC identifies correct drug-polymer solubility and miscibility for enantiotropic solid forms.
Authors: Bookwala M; School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave, Pittsburgh, PA 15282, USA., Shi J; Rigaku Americas Corporation, 9009 New Trails Dr, The Woodlands, TX 77381, USA., Buckner IS; School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave, Pittsburgh, PA 15282, USA., Bates S; Rigaku Americas Corporation, 9009 New Trails Dr, The Woodlands, TX 77381, USA., Wildfong PLD; School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave, Pittsburgh, PA 15282, USA. Electronic address: wildfongp@duq.edu.
Source: Journal of pharmaceutical sciences [J Pharm Sci] 2025 Jan; Vol. 114 (1), pp. 416-423. Date of Electronic Publication: 2024 Oct 18.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Country of Publication: United States NLM ID: 2985195R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6017 (Electronic) Linking ISSN: 00223549 NLM ISO Abbreviation: J Pharm Sci Subsets: MEDLINE
Imprint Name(s): Publication: 2016- : New York, NY : Elsevier
Original Publication: Easton, Pa., American Pharmaceutical Assn.
MeSH Terms: Solubility* , Calorimetry, Differential Scanning*/methods , X-Ray Diffraction*/methods , Crystallization*/methods , Polymers*/chemistry , Thermodynamics*, Vinyl Compounds/chemistry ; Povidone/chemistry ; Chemistry, Pharmaceutical/methods
Abstract: Thermodynamic properties, including solubility and miscibility, which are highly correlated with amorphous solid dispersion physical stability were identified for the complex solid forms of bromopropamide using simultaneous X-ray diffraction (XRD)-differential scanning calorimetry (DSC). The most stable solid form of bromopropamide was crystallized and its crystal structure was solved. The crystallized material was characterized using simultaneous XRD-DSC measurements, which allowed dual analyses of a single sample. Transitions of bromopropamide during heating resulted in observation of the unique diffraction patterns of its different solid forms. The dissolution endpoint (T end ) was measured for various mixtures of bromopropamide and polyvinylpyrrolidone-vinyl acetate random copolymer (PVPVA). The use of XRD-DSC allowed confident and accurate measurements of the T end for a large range of compositions, assisting in the estimation of drug-polymer solubility and miscibility. Thermodynamic properties identified using combined XRD-DSC were further compared to those obtained using only DSC data. It was found that DSC data in isolation can lead to ambiguity, misinterpretations, and incorrect conclusions, especially for a solid demonstrating multiple, closely related forms.
(Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest Duquesne University and Rigaku Americas Corporation jointly participated in data collection, writing, reviewing, and approving the publication. MB was a graduate student at Duquesne University. ISB and PLDW are professors at Duquesne University. JS and SB are employees of Rigaku Americas Corporation. The simultaneous XRD-DSC instrument used herein is the property of Rigaku Americas Corporation. Work at Rigaku was conducted as part of the Fellowship granted by Rigaku Americas Corporation and the National Institute of Pharmaceutical Technology and Education (NIPTE).
Contributed Indexing: Keywords: Amorphous solid dispersions; Dissolution endpoint; Enantiotropic solid forms; Physical stability; Polymorph-dependent solubility; Polymorphic transformation; Simultaneous XRD-DSC
Substance Nomenclature: 0 (Polymers)
0 (Vinyl Compounds)
FZ989GH94E (Povidone)
Entry Date(s): Date Created: 20241019 Date Completed: 20241222 Latest Revision: 20241222
Update Code: 20250114
DOI: 10.1016/j.xphs.2024.10.018
PMID: 39426565
Database: MEDLINE
Description
Abstract:Thermodynamic properties, including solubility and miscibility, which are highly correlated with amorphous solid dispersion physical stability were identified for the complex solid forms of bromopropamide using simultaneous X-ray diffraction (XRD)-differential scanning calorimetry (DSC). The most stable solid form of bromopropamide was crystallized and its crystal structure was solved. The crystallized material was characterized using simultaneous XRD-DSC measurements, which allowed dual analyses of a single sample. Transitions of bromopropamide during heating resulted in observation of the unique diffraction patterns of its different solid forms. The dissolution endpoint (T <subscript>end</subscript> ) was measured for various mixtures of bromopropamide and polyvinylpyrrolidone-vinyl acetate random copolymer (PVPVA). The use of XRD-DSC allowed confident and accurate measurements of the T <subscript>end</subscript> for a large range of compositions, assisting in the estimation of drug-polymer solubility and miscibility. Thermodynamic properties identified using combined XRD-DSC were further compared to those obtained using only DSC data. It was found that DSC data in isolation can lead to ambiguity, misinterpretations, and incorrect conclusions, especially for a solid demonstrating multiple, closely related forms.<br /> (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
ISSN:1520-6017
DOI:10.1016/j.xphs.2024.10.018