Influence of Excipients on Solvent-Mediated Hydrate Formation of Piroxicam Studied by Dynamic Imaging and Fractal Analysis
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文摘
Hydrate formation of pharmaceutical compounds can affect critical drug properties such as solubility and dissolution. There is, early in development, a need for a deeper understanding of how excipients influence hydrate formation mechanistically. The influence of excipients and of biorelevant medium on the kinetics of hydrate formation of piroxicam was studied with the aim of describing the kinetic changes of both the bulk suspension and the drug compact surface. Kinetic experiments were based on a miniaturized method using X-ray diffraction for solid-state analysis and ultra-high pressure liquid chromatography for drug concentration determination in bulk solution. Surface changes on drug compacts were monitored by dynamic image analysis of microscopic pictures and subsequent determination of a fractal dimension using box counting. Surface analysis correlated well with bulk monitoring of the piroxicam hydrate formation. Individual excipients exhibited highly specific effects on the kinetics of hydrate formation, but at equilibrium, the finally obtained fractal dimensions reached the same value of 1.85. The cluster structure of hydrate particles and therefore the recrystallization process were hardly affected by excipients; in contrast, excipients strongly affected the kinetics of hydrate formation, which is of pharmaceutical relevance.

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