Suihko E, Korhonen O, Järvinen T, Ketolainen J, Jarho P, Laine E, Paronen P
Department of Pharmaceutics, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland.
Int J Pharm. 2001 Mar 14;215(1-2):137-45. doi: 10.1016/s0378-5173(00)00682-7.
The physicochemical and tableting properties of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and its tolbutamide (TBM) complex were studied. The kinetics of TBM/HP-beta-CD inclusion complex formation in solution were determined by the phase solubility method. Solid complexes were prepared by freeze-drying and spray-drying. Water sorption-desorption behaviour of the materials were studied and compacts were made using a compaction simulator. TBM and HP-beta-CD formed 1:1 inclusion complexes in aqueous solution with an apparent stability constant of 63 M(-1). HP-beta-CDs and TBM/HP-beta-CD complexes were amorphous whereas the freeze-dried and spray-dried TBMs were polymorphic forms II and I, respectively. Sorption-desorption studies showed that HP-beta-CDs were deliquescent at high relative humidities. TBM/HP-beta-CD complexes had slightly lower water contents at low relative humidities than the physical mixtures. However, at high humidities their water sorption and desorption behaviours were similar to those of corresponding physical mixtures, indicating a glass transition of the complexed materials. TBM/HP-beta-CD complexes demonstrated a worse compactability than similarly prepared HP-beta-CDs or physical mixtures. Also particle properties that resulted from these preparation methods affected the compactability of the materials. In conclusion, the physicochemical and tableting properties of HP-beta-CD were modified by complexation it with TBM.
研究了羟丙基-β-环糊精（HP-β-CD）及其与甲苯磺丁脲（TBM）的复合物的物理化学性质和压片性能。采用相溶解度法测定了溶液中TBM/HP-β-CD包合物形成的动力学。通过冷冻干燥和喷雾干燥制备了固体复合物。研究了材料的水吸附-解吸行为，并使用压片模拟器制备了压片。TBM和HP-β-CD在水溶液中形成1:1的包合物，表观稳定常数为63 M⁻¹。HP-β-CD和TBM/HP-β-CD复合物为无定形，而冷冻干燥和喷雾干燥的TBM分别为II型和I型多晶型。吸附-解吸研究表明，HP-β-CD在高相对湿度下会潮解。TBM/HP-β-CD复合物在低相对湿度下的含水量略低于物理混合物。然而，在高湿度下，它们的水吸附和解吸行为与相应物理混合物相似，表明复合物质发生了玻璃化转变。TBM/HP-β-CD复合物的可压性比类似制备的HP-β-CD或物理混合物差。而且这些制备方法产生的颗粒性质影响了材料的可压性。总之，HP-β-CD与TBM复合后其物理化学性质和压片性能发生了改变。
