A miniaturized fluorescence assay on multi-well plates has been developed to study the solubility enhancement effect of (2-hydroxypropyl)-β-cyclodextrin on three anti-tumor alkaloids. The measurement of the fluorescence emission on a multi-well plate format has been proved to be a rapid and efficient technique to evaluate the solubility of pharmaceutical formulations of new drugs that help save time, reagents and wastes in the search for greener analytical strategies.
The proposed methodology was compared with a reference HPLC solubility study and was employed to examine the enhancement of the solubility of camptothecin, luotonin A, and a synthetic derivative of the latter in the presence of (2-hydroxypropyl)-β-cyclodextrin.
Considerable reductions in the time of analysis (almost 50 times faster) and the volume of organic solvents employed (close to 25 times less acetonitrile needed) were achieved. The nature of the inclusion complexes was investigated by analysis of the phase-solubility diagrams obtained by the newly developed method and was complemented with spectrofluorimetry and ESI-MS experiments.
The concentrations of solubilised compounds found by both methodologies were in good agreement (R2 > 0.98). The analytical figures of merit of both methodologies were compared and the adequacy of the proposed method for the development of drug solubilisation studies was discussed.
DOI: 10.1039/C3GC40974K, Paper
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A down-scaled high-throughput screening fluorescence assay for solubility studies achieves a 25-times reduction of organic solvent waste.
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