莪术醇固体分散体的制备及体外评价

Preparation and in vitro evaluation of curcumol solid dispersion

目的制备莪术醇固体分散体(Cur-SDs),优选最优处方及工艺,以期提高其体外溶出度。方法以体外溶出度为评价指标,分别考察以聚乙烯吡咯烷酮K30(PVP K30)、泊洛沙姆188(F68)、聚乙二醇4000(PEG4000)、聚乙二醇6000(PEG6000)为载体以及采用溶剂法、熔融法或溶剂-熔融法制备所得SDs对莪术醇的增溶能力。并利用红外光谱(IR)、差示扫描量热(DSC)、X-射线衍射(XRD)对SDs中药物的存在形态进行研究,并初步考察了其在长期储存过程中的稳定性。结果以F68为载体,采用溶剂-熔融法制备的Cur-SDs体外溶出行为优于其他处方、工艺制备的SDs,最优药物-载体比为1∶5。DSC、IR及XRD结果表明药物主要以分子或无定形状态存在于SDs中,且药物分子未发生变化。稳定性研究表明,室温放置6个月其溶出度未见下降、物相状态未见明显改变。结论将难溶性药物莪术醇制备成SDs,能显著提高其体外溶出度及溶出速率,且稳定性良好,工艺简单可行。

Objective Curcumol solid dispersions（Cur-SDs） were explored and the optimal formulation was selected for improving the in vitro dissolution of curcumol. Methods In this study, Cur-SDs were prepared by solvent method, fusion method and solvent-fusion method using F68, PVP K30, PEG4000, and PEG6000 as matrix, and in vitro dissolution rate was evaluated. Fourier transform infrared spectroscopy（IR）, differential scanning calorimetry（DSC）, and X-ray diffractometry（XRD） were employed to characterize the molecular arrangement of curcumol in SDs. And a brief investigation of its stability in the long-term storage process was also performed. Results The Cur-SD prepared with F68 as matrix and by solvent-fusion method was better in improving the invitro dissolution than those with other matrix or those prepared by other methods. Furthermore, the optimal drug-matrix ratio was 1∶5. DSC, IR and XRD indicated that the drug could be dispersed molecularly or amorphously in matrix, and no chemical reaction occurred. There was no decrease in its dissolution, and no significant change in molecular arrangement in a six-month stability study under room temperature. Conclusion The preparation of insoluble drug curcumol into solid dispersion can significantly improve its dissolution rate in vitro. Moreover, the preparation method is simple and feasible, and has good stability.