The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Tatiane Cogo MachadoN Rodríguez-Hornedo

Abstract

Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and Ksp values of 1:1 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolution, cocrystals regulate the interfacial pH (pHint) to 1.6 for MLX-MLE and 4.5 for MLX-SLC, therefore diminishing the cocrystal dissolution rate dependence on bulk pH. Do values ranged from 2 (pH 6.5) to 410 (pH 1.6) and w...Continue Reading

Citations

Oct 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kinga JóźwiakAleksander Filarowski
Jun 3, 2021·Pharmaceutics·Fucheng LengTom Leyssens
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li ZhangYang Lu
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ilma Nugrahani, Rismaya Desti Parwati

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