白藜芦醇-壳寡糖无定型固体分散体的制备与体外评价

Preparation and in Vitro Evaluation of Resveratrol-chitosan Oligosaccharide Amorphous Solid Dispersion

关键词:  白藜芦醇  壳寡糖  无定型固体分散体  溶解度  体外溶出  稳定性

Key words:  resveratrol  chitosan oligosaccharide  amorphous solid dispersion  solubility  in vitro dissolution  stability

摘要:

目的 将白藜芦醇（resveratrol，RES）和壳寡糖（chitosan oligosaccharide，COS）联合使用制备成白藜芦醇无定型固体分散体（RES-COS amorphous solid dispersion，RES-COS ASD），提高RES的体外溶出度。方法 通过球磨法制备RES-COS ASD，采用差示扫描量热分析、粉末X-射线衍射、扫描电镜和傅里叶红外光谱对制备的RES-COS ASD进行表征分析，对RES-COS ASD在漏槽和非漏槽条件下的体外溶出进行评价，并考察RES-COS ASD的物理稳定性。结果 差示扫描量热分析、粉末X-射线衍射结果表明，RES-COS ASD制备成功。扫描电镜观察发现该无定型固体分散体呈不规则块状、颗粒状，RES和COS的特征不可见。在RES-COS ASD （1∶4）、RES-COS ASD （1∶2）中，RES的饱和溶解度显著提高（P<0.01），分别为晶体RES原料药的2.37倍和2.29倍。漏槽条件下（20 min时），与RES原料药组相比，RES-COS ASD组中RES的累积溶出率显著提高（P<0.01）。非漏槽条件下体外溶出结果表明，与RES原料药相比，RES-COS ASD组中RES具有较高的体外溶出度，并且维持长时间的超饱和程度。另外，RES-COS ASD在25℃和40℃条件下，至少保持6个月的物理稳定性。结论 RES和COS联合使用制备的RES-COS ASD能够有效地改善RES的体外溶出度以及维持超饱和程度。

Abstract:

OBJECTIVE To improve in vitro dissolution of resveratrol(RES) through preparation of RES-chitosan oligosaccharide(COS) amorphous solid dispersion(RES-COS ASD). METHODS The RES-COS ASD was prepared by ball milling, characterized by differential scanning calorimetry(DSC), X-ray powder diffraction(XRPD), scanning electron microscopy(SEM) and Fourier transform infrared spectroscopy(FTIR). The dissolution of RES-COS ASD was evaluated in vitro under sink and non-sink conditions, and the physical stability of RES-COS ASD was investigated. RESULTS DSC and XRPD indicated that RES-COS ASD was successfully prepared. SEM showed that RES-COS ASD was irregular, lumpy and granular, and the characteristics of RES and COS were disappeared. For RES-COS ASD(1∶4) and RES-COS ASD(1∶2), the saturation solubility of RES was significantly increased(P<0.01), which was 2.37 times and 2.29 times of raw materials, respectively. The dissolution rate of RES in the RES-COS ASD was significantly higher than that in pure RES at 20 min under sink condition (P<0.01). Besides, compared with pure RES, RES-COS ASD exhibited significantly improvement in vitro non-sink dissolution and maintained supersaturated degree for a long time. In addition, RES-COS ASD maintained physical stability for at least 6 months at 25 ℃ and 40 ℃. CONCLUSION RES-COS ASD prepared by COS combination of RES can effectively improve the dissolution of RES and maintain supersaturated dissolution.