Predicted amorphous solubility and dissolution rate advantages following moisture sorption: Case studies of indomethacin and felodipine.
Int J Pharm
; 555: 100-108, 2019 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-30448307
ABSTRACT
Water is often readily absorbed by amorphous compounds, lowering their glass transition temperature (Tg) and facilitating their recrystallization (via nucleation-and-growth). At the same time, the increase in moisture content translates to a decrease in both the thermodynamic solubility and intrinsic dissolution rate, as compared to the corresponding dry (pure) amorphous phase, e.g. see [Murdande SB, Pikal MJ, Shanker RM, Bogner RH. 2010. Solubility advantage of amorphous pharmaceuticals I. A thermodynamic analysis. J Pharm Sci 991254-1264.]. In the case of pure indomethacin and felodipine, the solubility advantage of each amorphous phase over its crystalline counterpart were previously determined to be 7.6 and 4.7, respectively, using a new methodology together with basic calorimetric data taken from the literature. Herein, we demonstrate that, theoretically, following the uptake of just â¼0.5% w/w water, the solubility ratios decrease to 6.9 and 4.5, in the same order. Moreover, as the predicted intrinsic dissolution rate (based on the Noyes-Whitney equation) is directly proportional to the solubility advantage of a given amorphous-crystalline pair, it decreases proportionately upon moisture uptake. Applying the methodology presented herein, one can directly predict the extent of Tg-lowering observed at any moisture content, for a given amorphous phase. Knowing that value, it is possible to estimate the relative decrease in the solubility and/or intrinsic dissolution rate of the plasticized phase compared to the pure glass, and vice-versa.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Agua
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Felodipino
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Química Farmacéutica
/
Indometacina
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Año:
2019
Tipo del documento:
Article