摘要
目的:制备能够提高长春西汀(vinpocetine,VIN)分散状态和溶出速度的固体分散体(solid dispersion,SD),研究VIN在PVPK30中分散的热力学过程。方法:应用溶剂法制备长春西汀固体分散体,并采用差示扫描量热(DSC)分析及X射线衍射分析(X-RD),研究长春西汀在载体中的存在状态。采用溶出度法,考察不同比例的长春西汀、聚乙烯吡咯烷酮及柠檬酸制备的固体分散体对其体外溶出速度的影响,应用溶解度法测定VIN在PVPK30中分散过程的热力学参数。结果:DSC分析及X-RD分析结果表明长春西汀在载体PVPK30中以无定型形态存在。体外溶出结果表明长春西汀与聚乙烯吡咯烷酮比例为1:8和1:7之间时,长春西汀体外溶出速度最快,且两种比例无显著性差异。酸化剂的加入对长春西汀的溶出有一定促进作用,在试验范围内,VIN-PVPK30-SD表观稳定常数(Kc)随温度升高而减小,分散过程的△r H=-5.01k J/mol,△r S=-0.01 k J/mol,△r G<0。结论:加入酸化剂制备的VIN-PVP-CA-SD(1∶7∶0.5)可显著提高长春西汀的溶出速度,并提高了固体分散体的稳定性,VIN在PVPK30中的分散过程是放热过程且主要驱动力为焓驱动。
Objective： To prepare a solid dipersion（SD） of Vinpocetine（VIN）, which can enhance the state of dispersion and the rate of dissolution of VIN, and investigate the thermodynamics of VIN in PVPK30.Method： The co-precipitation was used to prepare the VIN-SDs. The dissolution characteristics in vitro of VIN-SD prepared with different ratio of PVPK30 and citric acid（CA） were studied. Differential scanning calorimetry（DSC） and powder X-ray diffraction（X-RD） analysis was utilized to test the physicochemical characteristics of VIN-SDs. The solubility and thermodynamic parameters of VIN in PVPK30 were determined by solubility techniques. Result： Powder X-ray diffraction and differential scanning calorimetry analysis confirmed that drugs were in the amorphous state in the carrier. When the ratio between VIN and PVP were 1∶7and 1∶8, the speed of dissolution of VIN-SDs was the best, and had no significant difference. And the dissolution of VIN-SD was improved by adding the acidulant. The apparent stability constant（Kc） was decreased as the temperature increased. In the reaction, △rH =-212.87 k J/mol, △rS=-0.57 k J/mol, △r G〈0. Conclution： The dissolution rate of VIN was significantly enhanced by the VIN-PVP-CA-SD（1∶7∶0.5） prepared with acidulant, and the stability of the SD（1：7：0.5） was improved. Thermodynamic studies indicated that VIN dispersing into PVPK30 is drived by the enthalpy.
出处
《浙江化工》
CAS
2016年第4期14-18,21,共6页
Zhejiang Chemical Industry
关键词
长春西汀
酸化剂
固体分散体
溶出度
表观稳定常数
热力学参数
Vinpocetine
acidulant
solid dispersion
dissolution rate
apparent stability constant
ther modynamic parameter
