Soluplus®、PVP VA64为载体的氟苯尼考固体分散体的制备及体外评价

Preparation and in Vitro Evaluation of Florfenicol Solid Dispersions with Soluplus® and PVP VA64 as Matrix

关键词:  氟苯尼考  固体分散体  溶解度  溶出度

Key words:  florfenicol  solid dispersion  solubility  dissolution

摘要:

目的 采用新型载体材料Soluplus^®和PVP VA64制备氟苯尼考固体分散体，以增加其溶解度及体外溶出度。方法 应用溶解度参数法初步预测药物与载体材料的相容性，进一步采用溶剂蒸发法制备氟苯尼考-Soluplus^®和氟苯尼考-PVP VA64固体分散体，并采用差示扫描量热法（DSC）、X-射线粉末衍射法（XPRD）、傅里叶变换红外光谱法（FTIR）对所得固体分散体进行表征，且与PVP K30进行比较。以溶解度和体外溶出度为评价指标，对不同载体制备的氟苯尼考固体分散体进行比较。结果 DSC、XPRD和FTIR结果表明，不同高分子材料制得的氟苯尼考固体分散体中药物均呈无定型状态；几种载体材料均能增加氟苯尼考的溶解度及溶出速率，增溶效果为PVP VA64>PVP K30>Soluplus^®，其中PVP VA64固体分散体的溶解度增加最为显著，25℃在标准硬水、自来水、纯化水中的溶解度约为原料药的3倍，且自来水中5 min时累积溶出率可达88.23%，为氟苯尼考原料药的20.56倍。结论 采用溶剂蒸发法制备氟苯尼考-PVP VA64固体分散体可以显著提高药物的溶解度及体外溶出度。

Abstract:

OBJECTIVE To prepare florfenicol solid dispersions(FF-SDs) with Soluplus^® and PVP VA64 as matrix to improve its solubility and in vitro dissolution. METHODS The solubility parameter method was used to predict the compatibility between florfenicol and carrier materials. Consequently, FF-SDs were prepared by solvent evaporation method with Soluplus^® and PVP VA64 as matrix, respectively; and characterized by differential scanning calorimetry(DSC), X-ray powder diffraction(XPRD) and fourier transform infrared spectroscopy(FTIR), and compared with FF-SDs with PVP K30 as matrix. The effects of different carriers on the solubility and in vitro dissolution of florfenicol in solid dispersions were compared. RESULTS The results of DSC, XPRD and FTIR showed that FF was amorphous after being prepared into solid dispersions. In addition, compared with florfenicol, the solubility and cumulative dissolution of FF-SDs were improved. The efficiency of solubilization was as follows:PVP VA64>PVP K30>Soluplus^®. Especially, FF-SD with PVP VA64 as matrix could enhance the solubility remarkably. The solubility was about 3 times of free florfenicol in standard hard water, tap water, and purified water at 25℃, and the cumulative dissolution reached 88.23% at 5 min in hard water, which was 20.56 folds of florfenicol. CONCLUSION The FF-SDs prepared with PVP VA64 as matrix by solvent evaporation method can significantly enhance the solubility and dissolution of florfenicol.