Zhao Xue-ling, Li Qiang, Gong Xian-feng, Li San-ming
Department of Pharmaceutical Science and Engineering, Heilongjiang University, Harbin 150080, China.
Yao Xue Xue Bao. 2007 Feb;42(2):226-30.
To investigate the delivery mechanism of micro-porous osmotic pump tablets ( MPOP), taking tramadol hydrochloride ( TR) as the model drug, tramadol hydrochloride micro-porous osmotic pump tablets (TR MPOP) were prepared with compressible starch as diluent, cellulose acetate as coating material, polyethylene glycol 400 as pore-forming agents. The equilibrium solubility and osmolality of TR were determined. The effects of fillers in tablet cores, coating levels, and osmotic pressures of release media on expansion behavior of preparations were described. The influences of the category, osmolality, and pH value of release media, release methods, and release conditions on release curves of tablets were evaluated. Based on several models, the delivery pattern of TR MPOP was fitted. The equilibrium solubility in water and osmolality of TR were (775.8 +/- 17.7) g x L(-1) and 4.036 Osmol x kg(-1), respectively. During the drug-release period, it was observed that the tablets expanded markedly in response to the expansion characteristics of compressible starch and the osmotic pressure difference across the membrane. When osmotic pressure of release media increased, the significant change of the equilibrium solubility of TR was not found, but the release rates of TR MPOP decreased significantly. The delivery rate was not influenced by the pH of release mediums, dissolution methods and paddle stirring rates. The drug release profile conformed to the model of zero order in 8 h. The pore-forming agents were dissolved in release medium, which caused micro-pores. The expansion of tablets made the size of micropores bigger, and then the drug-releasing pores were obtained. It was proved that the drivers of drug delivering from TR MPOP were mainly the difference of osmotic pressure, and secondly the difference of solubility. TR MPOP were the controlled-release preparation.
以盐酸曲马多(TR)为模型药物,以可压性淀粉为稀释剂、醋酸纤维素为包衣材料、聚乙二醇400为致孔剂,制备盐酸曲马多微孔渗透泵片(TR MPOP),考察其释药机制。测定TR的平衡溶解度和渗透压。描述片芯填充剂、包衣层厚度及释放介质渗透压对制剂膨胀行为的影响。评价释放介质种类、渗透压、pH值、释放方法及释放条件对片释药曲线的影响。基于多种模型拟合TR MPOP的释药模式。TR在水中的平衡溶解度和渗透压分别为(775.8±17.7)g·L⁻¹和4.036 Osmol·kg⁻¹。在药物释放期,观察到片剂因可压性淀粉的膨胀特性和膜两侧的渗透压差异而显著膨胀。当释放介质渗透压增加时,TR的平衡溶解度未发现显著变化,但TR MPOP的释放速率显著降低。释药速率不受释放介质pH值、溶出方法及桨板搅拌速率的影响。药物释放曲线在8 h内符合零级模型释药。致孔剂在释放介质中溶解形成微孔,片剂膨胀使微孔尺寸增大,从而形成药物释放孔道。结果表明,TR MPOP释药的驱动力主要是渗透压差异,其次是溶解度差异。TR MPOP为控释制剂。