Jug Mario, Bećirević-Laćan Mira
Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Drug Dev Ind Pharm. 2004;30(10):1051-60. doi: 10.1081/ddc-200040245.
The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with beta-cyclodextrin (beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, Ks, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug-CD and drug-CD-polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta-potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.
本研究的目的是研究羟丙基甲基纤维素(HPMC)对吡罗昔康(PX)与β-环糊精(β-CD)和二甲基-β-环糊精(DM-β-CD)在溶液和固态下络合的影响。相溶解度研究表明该聚合物对药物络合有积极作用。三元络合物稳定性常数Ks值的提高清楚地证明了添加HPMC对提高络合效率的益处。通过喷雾干燥制备了固体二元和三元络合物。通过差示扫描量热法(DSC)、ζ电位测量和粒度分布研究了药物 - CD和药物 - CD - 聚合物在固态下的相互作用。即使在二元和三元络合物中也观察到PX溶解速率显著增加。三元络合物中HPMC的存在略微延缓了PX的释放。环糊精络合增加了半透膜上的PX浓度梯度,导致PX通量增加。PX向膜界面的扩散受阻降低了三元络合物的PX通量值。