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Purpose.
The main objective of the study was to determine the ability of microthermal analysis (μTA) to assess the crystallinity of the drug in two noncommercial pharmaceutical solid dispersions.
Methods.
Pure substances, physical mixes, and solid dispersions were analyzed by μTA. The thermal values obtained by μTA were compared with data obtained by more conventional techniques like differential scanning calorimetry.
Results.
μTA was able to detect the drug in the waxy matrix. The technique was capable of showing that relatively large amorphous drug domains (up to 70 μm) are formed during the solidification of the solid dispersion. These amorphous domains are thermodynamically unstable and can crystallize upon aging.
Conclusions.
μTA was successfully applied to the physical characterization of solid dispersions. Local thermal analysis (LTA) offers a unique way to probe a selected area on the surface of the sample. It is capable of melting the drug locally without melting the lower melting point excipient. These results gave an understanding of the poor dissolution performance of these solid dispersions upon aging.
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Abbreviations
- LTA:
-
local thermal analysis
- MDSC:
-
modulated differential scanning calorimetry
- PEG:
-
polyethylene glycol
- PXRD:
-
powder X-ray diffraction
- TPGS:
-
d-α tocopheryl polyethylene glycol 1000 succinate
- μTA:
-
microthermal analysis
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Galop, M. Study of Pharmaceutical Solid Dispersions by Microthermal Analysis. Pharm Res 22, 293–302 (2005). https://doi.org/10.1007/s11095-004-1197-z
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DOI: https://doi.org/10.1007/s11095-004-1197-z