Tantishaiyakul V, Kaewnopparat N, Ingkatawornwong S
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand.
Int J Pharm. 1999 Apr 30;181(2):143-51. doi: 10.1016/s0378-5173(99)00070-8.
Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug.
采用溶剂法,以聚乙烯吡咯烷酮(PVP)K - 17 PF和PVP K - 90制备了吡罗昔康固体分散体。通过X射线衍射、傅里叶变换红外(FTIR)光谱和差示扫描量热法(DSC)对固体分散体和物理混合物的物理状态以及药物与PVP的相互作用进行了表征。FTIR分析表明,在固体分散体中吡罗昔康与PVP之间存在分子间氢键。这些相互作用反映了吡罗昔康晶体结构的变化。通过吡罗昔康N - H或O - H峰的消失,可以预测PVP部分内的无定形状态在吡罗昔康分散体中存在。溶出度研究表明,吡罗昔康分散在PVP中时溶出度显著增加。低分子量的PVP K - 17比高分子量的PVP K - 90取得了更好的结果。PVP K - 17中的非无定形固体分散体显示出与PVP K - 90中的无定形分散体几乎相同快的溶出速率。由于PVP K - 90的粘度非常高,PVP K - 90中固体分散体的溶出机制主要是扩散控制。含药物与PVP K - 17比例为1:5和1:6的无定形固体分散体溶出度最大,与纯药物相比,在5分钟内溶出度增加了40倍。