Jürgens K, Müller B W
Department for Pharmaceutics and Biopharmaceutics, Christian-Albrecht-University Kiel, Germany.
Pharmazie. 2005 Sep;60(9):665-70.
The parenteral application of active substances with poor solubility in water is often bound to the use of stabilizing excipients or surfactants with serious undesired side effects. A new concept is introduced based on a drug concentrate, comprising the active substance dissolved in parenterally acceptable organic solvents, and an aqueous dilution medium, which are mixed in a special mixing device immediately prior to application and thus generating the applicable formulation directly prior to administration. Due to the requirement of formulation stability for only a few minutes, the amount of stabilizing agents can be reduced significantly. It can be shown that model drugs dissolved in a mixture of polyoxyethylen glycol, ethanol and soya lecithin as stabilizer may be mixed to an aqueous glucose solution resulting in a parenterally acceptable and administerable dispersion which is physically stable for several minutes. First in vivo data show good tolerability and blood plasma levels which are comparable to conventional solutions.
对于在水中溶解度较差的活性物质，肠胃外给药往往需要使用具有严重不良副作用的稳定辅料或表面活性剂。基于药物浓缩物引入了一种新概念，该药物浓缩物包括溶解在肠胃外可接受有机溶剂中的活性物质和水性稀释介质，在给药前立即在特殊混合装置中混合，从而在给药前直接生成适用制剂。由于制剂仅需几分钟的稳定性，稳定剂的用量可显著减少。可以证明，溶解在聚乙二醇、乙醇和大豆卵磷脂混合物中作为稳定剂的模型药物可与葡萄糖水溶液混合，得到肠胃外可接受且可给药的分散体，其在物理上可稳定几分钟。首批体内数据显示出良好的耐受性，血浆水平与传统溶液相当。
