Preparation Of Two Conazoles Nanosuspensions Freeze-dried Powder And The Mechanism Discussion Of The Increased Dissolution Rate

Both fluconazole (FN) and econazole nitrate (ENN) are triazole antifungal drug. Owing to their low aqueous solubility, the drug dissolution rates are limited. In this work, we prepared nanosuspensions freeze-dried powder of FN and ENN in order to improve their dissolution rate.In this paper, the research contents and research results are as follows:一、Preparation, characterization of FN nanosuspensions freeze-dried powder and the possible mechanism of the increased dissolution rate.FN nanosuspension was prepared by the solvent diffusion method, where metha-nol worked as organic solvent and the mixture of tween80and span20worked as dispersant. FN nanosuspension freeze-dried powder could be obtained adding mannitol to the FN nanosuspension as a cryoprotectant and then freezed at-90℃till it was dried.The results of scanning electron microscope (SEM) showed that the redispersed freeze-dried powder were round and uniform with the particle sizes about100nm. The freeze-dried nanosuspensions powders were left alone for two days, seven days, fifteen days, thirty days, one hundred eighty days, three hundred sixty days, and redispersed respectively. It was found that the particle size, PDI and Zeta potential were almost the same. The dissolution testing revealed that more than86%FN in the freeze-dried powder was released at140min. For FN nanosuspensions freeze-dried powder, it was found that the one FN molecule and one water molecule could form a monohydrate by single crystal X-ray diffractometry method. We guessed that the mechanism of increasing the dissolution rate of FN may be related with mannitol, and FN dissolved in the surface of the mannitol. Through the role of polar alcohol hydroxyl, FN were more likely to contact with the water and formed a monohydrate.二、Preparation, characterization of EN nanosuspensions freeze-dried powder and the possible mechanism of the increased dissolution rateEthanol worked as organic solvent, the sodium dodecyl sulfate (SDS) worked as surfactant, and the poloxamer188worked as cryoprotectant. The results of scanning electron microscope (SEM) showed that the redispersed freeze-dried powder were uniform with the particle sizes about100nm. The freeze-dried nanosuspensions powders were saved for two days, seven days, fifteen days, thirty days, one hundred eighty days, three hundred sixty days, and redispersed respectively. It was found that the particle size, PDI and Zeta potential were almost the same. The dissolution rate testing revealed that more than91%ENN in the freeze-dried powder was released at140min. For ENN nanosuspensions freeze-dried powder, it was found that the one ENN molecule and one SDS molecule could form hydrogen bonds by single crystal X-ray diffractometry method. We guessed that the mechanism of increasing the dissolution rate of ENN may be related with SDS. ENN and SDS can form a hydrogen bond, and ENN was pulled into water by the hydrophilic group on the other side of SDS. the cryoprotectant poloxamer188made the redispersed nanosuspensions suspended, which also increased the dissolution rate of ENN.