Fernandes Catarina Marques, Veiga Francisco José Baptista
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Chem Pharm Bull (Tokyo). 2002 Dec;50(12):1597-602. doi: 10.1248/cpb.50.1597.
The inclusion ability of triacetyl-beta-cyclodextrin (TAbetaCD), a hydrophobic cyclodextrin (CD) derivative was examined, using nicardipine hydrochloride (NC) as model drug. The binary compounds were prepared in a 1 : 1 molar ratio by the kneading and the spray-drying techniques. In order to confirm the complexation between NC and TAbetaCD in the solid state, differential scanning calorimetry, X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscopy were carried out and the results were compared with the corresponding physical mixture in the same molar ratio. The kneaded product presented only slight modifications on the drug physicochemical and morphological properties, which could mean that no complex formation occurred during this process. In contrast, spray-drying was found to produce inclusion complexes with amorphous nature. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the United States Pharmacopoeia (USP) basket method. The NC in vitro release from the kneaded and spray-dried products was markedly retarded in both dissolution media. However, this retarding effect was significantly more evident for the spray-dried compound. It was concluded that the formation of real inclusion complexes could only be achieved by the spray-drying method.
以盐酸尼卡地平（NC）为模型药物，考察了疏水性环糊精（CD）衍生物三乙酰基-β-环糊精（TAbetaCD）的包合能力。通过捏合和喷雾干燥技术，以1:1的摩尔比制备二元化合物。为了确认固态下NC与TAbetaCD之间的络合作用，进行了差示扫描量热法、X射线衍射法、傅里叶变换红外光谱法和扫描电子显微镜检查，并将结果与相同摩尔比的相应物理混合物进行比较。捏合产物在药物理化性质和形态上仅表现出轻微变化，这可能意味着在此过程中未形成络合物。相比之下，发现喷雾干燥可产生具有无定形性质的包合物。根据美国药典（USP）篮法，在模拟胃液（pH 1.2）和肠液（pH 6.8）中进行体外溶出度研究。在两种溶出介质中，捏合和喷雾干燥产物中NC的体外释放均明显延迟。然而，这种延迟作用在喷雾干燥化合物中更为明显。得出结论，只有通过喷雾干燥法才能形成真正的包合物。
