Corti Giovanna, Capasso Gaetano, Maestrelli Francesca, Cirri Marzia, Mura Paola
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Florence, via U.Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
J Pharm Biomed Anal. 2007 Nov 5;45(3):480-6. doi: 10.1016/j.jpba.2007.07.018. Epub 2007 Jul 20.
Interaction products of metformin hydrochloride (MF.HCl), an oral anti-hyperglycaemic agent highly soluble in water, with triacetyl-beta-cyclodextrin (TAbetaCyD), a hydrophobic CyD derivative practically insoluble in water, were prepared to evaluate their suitability for the development of a sustained-release dosage form of the drug. Equimolar MF.HCl-TAbetaCyD solid compounds were obtained by different techniques, i.e., physical mixing, kneading, co-grinding, sealed-heating, and spray-drying, in order to investigate and compare their effectiveness and influence on the physical-chemical properties of the final products. Differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used for the solid-state characterization of the different MF.HCl-TAbetaCyD systems, whereas their in vitro dissolution properties were determined according to the dispersed amount method. According to the results of solid-state studies, the ability of the different preparation methods to promote effective interactions between drug and CyD varied in the order: spray-drying>co-grinding>kneading>sealed-heating approximately physical mixing. The same effectiveness rank order was observed also in dissolution studies. In fact the time to dissolve 100% drug varied increased from 1 min, for pure drug, to 3, 7, 40, 120 up to 420 min for physically mixed, sealed-heated, kneaded, co-ground and spray-dried products, respectively. Thus the drug-TA(CyD products obtained by spray drying and co-grinding were selected as the best candidates for the future development of a suitable prolonged-release oral dosage form of MF.HCl.
盐酸二甲双胍（MF.HCl）是一种极易溶于水的口服抗高血糖药物，它与三乙酰-β-环糊精（TAbetaCyD）（一种实际上不溶于水的疏水性环糊精衍生物）的相互作用产物被制备出来，以评估它们对于开发该药物缓释剂型的适用性。通过不同技术，即物理混合、捏合、共研磨、密封加热和喷雾干燥，获得了等摩尔的MF.HCl-TAbetaCyD固体化合物，以便研究和比较它们的有效性以及对最终产品物理化学性质的影响。差示扫描量热法、X射线粉末衍射法、傅里叶变换红外光谱法和扫描电子显微镜用于不同MF.HCl-TAbetaCyD体系的固态表征，而它们的体外溶出特性则根据分散量法测定。根据固态研究结果，不同制备方法促进药物与环糊精之间有效相互作用的能力按以下顺序变化：喷雾干燥＞共研磨＞捏合＞密封加热≈物理混合。在溶出研究中也观察到了相同的有效性排序。实际上，药物溶解100%的时间从纯药物的1分钟增加到物理混合、密封加热、捏合、共研磨和喷雾干燥产品的分别为3、7、40、120直至420分钟。因此，通过喷雾干燥和共研磨获得的药物-TA（环糊精）产品被选为未来开发合适的MF.HCl长效口服剂型的最佳候选物。
