Solid-state analysis of amorphous solid dispersions: Why DSC and XRPD may not be regarded as stand-alone techniques

Autor: Bjorn Vergauwen, Christophe Huygens, Timothy Pas, Guy Van den Mooter, Sien Dedroog
Rok vydání: 2020
Předmět:
Fenofibrate (3339)
Hot Temperature
Polymers
Chemistry
Pharmaceutical
Clinical Biochemistry
Pharmaceutical Science
Ketoconazole (456201)
XRPD
Sensitivity and Specificity
01 natural sciences
Analytical Chemistry
(M)DSC
Crystallinity
Differential scanning calorimetry
X-Ray Diffraction
Phase (matter)
Drug Discovery
Technology
Pharmaceutical
Dissolution
Spectroscopy
Cryo-milling
chemistry.chemical_classification
Calorimetry
Differential Scanning
010405 organic chemistry
Chemistry
Indomethacin (3715)
Spray drying
010401 analytical chemistry
Hot melt extrusion
Polymer
0104 chemical sciences
Amorphous solid
Solubility
Chemical engineering
Solvents
Nanoparticles
Griseofulvin (441140)
Powders
Crystallization
Amorphous solid dispersions
Itraconazole (55283)
Dispersion (chemistry)
Naproxen (156391)
Powder diffraction
Zdroj: Journal of Pharmaceutical and Biomedical Analysis. 178:112937
ISSN: 0731-7085
DOI: 10.1016/j.jpba.2019.112937
Popis: Amorphous solid dispersions (ASDs) are single-phase amorphous systems, where drug molecules are molecularly dispersed (dissolved) in a polymer matrix. The molecular dispersion of the drug molecules is responsible for their improved dissolution properties. Unambiguously establishing the phase behavior of the ASDs is of utmost importance. In this paper, we focused on the complementary nature of (modulated) differential scanning calorimetry ((m)DSC) and X-ray powder diffraction (XRPD) to elucidate the phase behavior of ASDs as demonstrated by a critical discussion of practical real-life examples observed in our research group. The ASDs were manufactured by either applying a solvent-based technique (spray drying), a heat-based technique (hot melt extrusion) or mechanochemical activation (cryo-milling). The encountered limiting factors of XRPD were the lack of sensitivity for small traces of crystallinity, the impossibility to differentiate between distinct amorphous phases and its impossibility to detect nanocrystals in a polymer matrix. In addition, the limiting factors of (m)DSC were defined as the well-described heat-induced sample alteration upon heating, the interfering of residual solvent evaporation with other thermal events and the coinciding of enthalpy recovery with melting events. In all of these cases, the application of a single analytical technique would have led to erroneous conclusions, whilst the combination of (m)DSC and XRPD elucidated the true phases of the ASD. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:178 ispartof: location:England status: published
Databáze: OpenAIRE
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