Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 93, Issue -, Pages 88-94Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2015.01.029
Keywords
Poorly soluble pharmaceutical; Phase behaviour; Indomethacin; PLGA; Copolymer; Thermodynamic model; PC-SAFT; Kwei-equation
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Funding
- CLIB-Graduate Cluster Industrial Biotechnology
- Alexander von Humboldt-Foundation
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In the current study, the phase behaviour of indomethacin and poly(lactic-co-glycolic acid) (PLGA) formulations was investigated as a function of the molecular weight and the copolymer composition of PLGA. The formulations were prepared by ball milling, and the phase behaviour, comprised of the glass-transition temperature of the formulations and the solubility of indomethacin in PLGA, was measured using modulated differential scanning calorimetry (mDSC). The results determined that the solubility of indomethacin in PLGA at room temperature was very low and increased with a corresponding decrease in the molecular weight of PLGA. The copolymer composition of PLGA had a minor effect on the indomethacin solubility. The effect of PLGA's molecular weight and copolymer composition on the solubility of indomethacin could be modelled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with a high degree of accuracy when compared with the experimental data. The glass-transition temperatures had a negative deviation from the weighted mean of the glass-transition temperatures of the pure substances, which could be described by the Kwei-equation. (C) 2015 Published by Elsevier B.V.
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