Mechanism of drug dissolution rate enhancement from beta-cyclodextrin-drug systems

The influence of beta-cyclodextrin on the physicochemical properties of bendrofluazide, chlorothiazide, hydrochlorothiazide and hydroflumethiazide was investigated using solubility, X-ray powder diffraction, differential scanning calorimetry (DSC) and intrinsic dissolution rate methods. The solubility of each drug was enhanced in the presence of beta-cyclodextrin, the effect being greatest with bendrofluazide. X-ray diffraction data on equimolar freeze dried systems indicated the formation of solid state inclusion complex only in the case of bendrofluazide. The relative increase in initial dissolution rate of drug from freeze dried systems varied from sixty fold for bendrofluazide to three fold for hydroflumethiazide. The observed dissolution rates were intermediate between those predicted by the classical two component soluble complex model and a carrier controlled model. It was concluded that the enhanced drug dissolution rates, which are above those predicted by the soluble complex model, are due to an extension of carrier phase dissolution control to higher drug weight fractions than predicted by the soluble complex model and that this was a consequence of the disparate solubilities of the carrier and drug.