ËÄÉ«AV

Our primary objective is to characterize theÌýself-associationÌý´Ç´ÚÌýrafoxanideÌýin alkalineÌýmedia. The second objective is to illustrate the feasibility of usingÌýrafoxanideÌýmicellar solution as the feed solution to prepareÌýamorphousÌýsolidÌýdispersion via spray drying.ÌýRafoxanideÌýis a poorly water-soluble drug. It is a weak acid, and its poorÌýaqueousÌýsolubility is due to its hydrophobicity. The surface-active property ofÌýrafoxanideÌýhas not been previously reported. It was discovered that the addition of a small percentage of organic solvents is required to elevate the solubility ofÌýrafoxanideÌýabove the critical micelle concentration to allow for the formation of micelles. Our fluorescence decay study confirms theÌýself-associationÌý´Ç´ÚÌýrafoxanideÌýin a cosolvent consisting of 70%, v/v, NaOH solution and 30%, v/v, acetone. The position of each functional group in the micellar structures using theÌý¹H NMR technique was identified. The critical micelle concentration ofÌýrafoxanideÌýin the cosolvent is determined to be 302 μg/mL using a surface tension method. The solubility ofÌýrafoxanideÌýin 0.1 N NaOH solution is less than 11 μg/mL. Interestingly, the apparent solubility increased to 38,400 μg/mL in the presence of 30% acetone as the result of micelle formation. This unique solubility characteristic makes it feasible to prepareÌýrafoxanideÌýamorphoussolidÌýdispersionsÌýby spray drying a predominantlyÌýaqueousÌý(70% 0.1 N NaOH solution and 30% acetone) based feed solution. Povidone and copovidone were both used as polymeric carriers. Based onÌýsolid-state characterization, including differential scanning calorimetry, X-ray powder diffraction, and hot-stage polarized light microscopy, our results indicate thatÌýrafoxanideÌýsoliddispersionsÌýprepared using this novel process areÌýamorphous. Approximately 750-fold increase in the concentration ofÌýrafoxanideÌýinÌýaqueousÌýmediaÌýat pH 6.8 was achieved with theÌýamorphousÌýsolidÌýdispersions.