Janjikhel R K, Adeyeye C M
Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
J Microencapsul. 1997 Jul-Aug;14(4):409-26. doi: 10.3109/02652049709033826.
Ibuprofen microspheres were prepared from the racemate, (+)-S and (-)-R enantiomers using waxes such as ceresine and glyceryl stearate and stereospecifically characterized. The method of preparation of the microspheres was a hydrophobic congealable disperse phase encapsulation process and variables such as particle size, wax type, enantiomeric form were evaluated. Dissolution studies were carried out by a modified USP type II method and the samples were analysed by a stereospecific HPLC assay using S-(-)-1(1) naphthylethylamine as the derivatizing agent and fenoprofen as the internal standard. The mean particle sizes of (+)-S and (-)-R enantiomers determined by microscopy/image analysis were 64 and 99 microns respectively while that of the racemate was 48 microns. Differential Scanning Calorimetry (DSC) of ibuprofen and the enantiomers showed endothermic peaks at 72 and 55 degrees C respectively. Thermograms of the physical mixture and microspheres did not show the characteristic ibuprofen peak, indicating a change in crystallinity of the drug. Powder X-ray diffraction patterns of the enantiomers and racemic ibuprofen were found to be dissimilar indicating different crystal properties. The X-ray patterns for the microspheres did not show the characteristic peaks for the drug indicating that ibuprofen may be in solid solution with the waxes. Scanning electron micrographs of the microspheres showed a generally smooth and spongy appearance for the microspheres made of compritol and glyceryl stearate. Microspheres made from the paraffin waxes had rough and hard surface characteristics consistent with the higher melting point of the waxes. Ceresine microspheres made with the enantiomers had a rougher and more porous surface compared to the microspheres made with racemic ibuprofen. Stereospecific release of the recemate from the formulations was found to be sustained (T25 of 4 h), while release from the enantiomers was less sustained (T50 of 2 h). From the S:R ratios and statistical analysis of the data, the release of the enantiomers of ibuprofen from the formulations containing the racemate was found to be non-stereoselective.
使用诸如微晶蜡和硬脂酸甘油酯等蜡，由外消旋体、（+）-S和（-）-R对映体制备布洛芬微球，并对其进行立体特异性表征。微球的制备方法是疏水可凝结分散相包封法，并评估了诸如粒径、蜡类型、对映体形式等变量。采用改良的美国药典II型方法进行溶出度研究，并使用S-（-）-1（1）萘乙胺作为衍生剂、非诺洛芬作为内标，通过立体特异性高效液相色谱法对样品进行分析。通过显微镜/图像分析测定，（+）-S和（-）-R对映体的平均粒径分别为64微米和99微米，而外消旋体的平均粒径为48微米。布洛芬及其对映体的差示扫描量热法（DSC）分别在72℃和55℃显示吸热峰。物理混合物和微球的热重曲线未显示出布洛芬的特征峰，表明药物的结晶度发生了变化。发现对映体和外消旋布洛芬的粉末X射线衍射图谱不同，表明晶体性质不同。微球的X射线图谱未显示出药物的特征峰，表明布洛芬可能与蜡形成固溶体。微球的扫描电子显微镜照片显示，由硬脂醇和硬脂酸甘油酯制成的微球通常外观光滑且呈海绵状。由石蜡制成的微球具有粗糙且坚硬的表面特征，这与蜡的较高熔点一致。与由外消旋布洛芬制成的微球相比，由对映体制成的微晶蜡微球表面更粗糙且孔隙更多。发现制剂中外消旋体的立体特异性释放是持续的（T25为4小时），而对映体的释放持续性较差（T50为2小时）。根据S:R比值和数据统计分析，发现含有外消旋体的制剂中布洛芬对映体的释放是非立体选择性的。
