Roston D A, Sun J J, Collins P W, Perkins W E, Tremont S J
Searle Research and Development, Skokie, Illinois 60077, USA.
J Pharm Biomed Anal. 1995 Nov;13(12):1513-20. doi: 10.1016/0731-7085(95)01588-4.
We have recently been involved in the development of a method for assaying the active component in a controlled-release drug formulation, which is composed of a drug substance covalently bonded to polymer matrix. The drug substance in the formulation is the active enantiomer of misoprostol, a synthetic analog of natural prostaglandins and the active ingredient in Cytotec. Our method development consisted of a systematic evaluation of dynamic, off-line supercritical fluid extraction (SFE) as sample preparation for the formulation assay. Extracts were analyzed with normal phase and reversed-phase HPLC methods. The reversed-phase system utilized postcolumn reaction to provide selective detection of the extracted prostaglandin sample components. Several SFE parameters were investigated to optimize the recovery of the drug substance from the formulation, including sample quantity, extraction cell volume, extraction duration, supercritical carbon dioxide modifier, temperature, pressure, and collection solvent. The SFE experiments were completed with a commercially available multicell extractor. Preliminary validation studies utilized a formulation made with radiolabeled drug to determine the recovery achieved under the optimized SFE conditions and assessed the precision of replicate determinations. Analysis was completed under the optimized conditions to quantitate levels of the active component and related compounds in lots of the experimental polymeric formulation and to determine the total weight per cent extracted.
我们最近参与了一种用于测定控释药物制剂中活性成分的方法的开发，该制剂由与聚合物基质共价结合的药物组成。制剂中的药物是米索前列醇的活性对映体，米索前列醇是天然前列腺素的合成类似物，也是喜克溃中的活性成分。我们的方法开发包括对动态离线超临界流体萃取（SFE）进行系统评估，作为制剂分析的样品制备方法。提取物用正相和反相高效液相色谱法进行分析。反相系统利用柱后反应对提取的前列腺素样品成分进行选择性检测。研究了几个SFE参数以优化药物从制剂中的回收率，包括样品量、萃取池体积、萃取持续时间、超临界二氧化碳改性剂、温度、压力和收集溶剂。SFE实验使用市售的多池萃取器完成。初步验证研究使用含放射性标记药物的制剂来确定在优化的SFE条件下实现的回收率，并评估重复测定的精密度。在优化条件下完成分析，以定量实验性聚合物制剂批次中活性成分和相关化合物的含量，并确定提取的总重量百分比。
