Van Eerdenbrugh Bernard, Froyen Ludo, Van Humbeeck Jan, Martens Johan A, Augustijns Patrick, Van Den Mooter Guy
Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Leuven, Belgium.
Eur J Pharm Sci. 2008 Nov 15;35(4):344-53. doi: 10.1016/j.ejps.2008.08.003. Epub 2008 Aug 14.
Four alternative matrix formers [Avicel PH101, Fujicalin (CaHPO(4)), Aerosil 200 (SiO(2)) and Inutec SP1] were evaluated for their capability in preserving rapid dissolution after spray-drying of nanosuspensions. Model drug compounds selected were cinnarizine (CIN), itraconazole (ITR) and phenylbutazone (PHB) as they showed a decrease in dissolution rate upon spray-drying in the absence of additional matrix formers, yielding release values after 5min of dissolution (release(5min)) of 57.7+/-1.0% (CIN), 56.3+/-3.8% (ITR) and 67.4+/-1.3% (PHB). Compared to the situation without matrix former inclusion, the performance of Avicel PH101 was good for CIN (release(5min)=90.9+/-7.7%), intermediate for PHB (release(5min)=81.0+/-6.4%) and poor for ITR (release(5min)=42.1+/-4.2%). For Fujicalin, intermediate (PHB: release(5min)=87.7+/-3.0%) or poor (CIN: release(5min)=66.1+/-3.4%; ITR: release(5min)=55.9+/-5.2%) performance was seen. Results for Aerosil 200 were good for all compounds (CIN: release(5min)=91.5+/-2.5%; ITR: release(5min)=83.8+/-3.4%; PHB: release(5min)=95.5+/-2.4%), indicating that the large specific surface area was in this case translated into good matrix forming capabilities. Finally, the best results were obtained for Inutec SP1 (CIN: release(5min)=88.7+/-1.2%; ITR: release(5min)=93.4+/-2.4%; PHB: release(5min)=101.3+/-4.9%). Except for Avicel PH101, Cl-maps from X-ray microanalysis of the itraconazole powders supported the hypothesis that better dispersion of drug in the powders results in faster dissolution.
评估了四种替代型基质形成剂[微晶纤维素PH101、富山纤维素（磷酸氢钙）、气相二氧化硅200（二氧化硅）和益他敏SP1]在喷雾干燥纳米混悬液后保持快速溶解的能力。所选的模型药物化合物为桂利嗪（CIN）、伊曲康唑（ITR）和保泰松（PHB），因为在没有额外基质形成剂的情况下，它们在喷雾干燥后溶解速率降低，在溶解5分钟后的释放值（release(5min)）分别为57.7±1.0%（CIN）、56.3±3.8%（ITR）和67.4±1.3%（PHB）。与未加入基质形成剂的情况相比，微晶纤维素PH101对CIN的性能良好（release(5min)=90.9±7.7%），对PHB中等（release(5min)=81.0±6.4%），对ITR较差（release(5min)=42.1±4.2%）。对于富山纤维素，观察到中等性能（PHB：release(5min)=87.7±3.0%）或较差性能（CIN：release(5min)=66.1±3.4%；ITR：release(5min)=55.9±5.2%）。气相二氧化硅200对所有化合物的结果都很好（CIN：release(5min)=91.5±2.5%；ITR：release(5min)=83.8±3.4%；PHB：release(5min)=95.5±2.4%），表明在这种情况下，大比表面积转化为良好的基质形成能力。最后，益他敏SP1获得了最佳结果（CIN：release(5min)=88.7±1.2%；ITR：release(5min)=93.4±2.4%；PHB：release(5min)=101.3±4.9%）。除了微晶纤维素PH101外，伊曲康唑粉末的X射线微分析中的Cl图谱支持了药物在粉末中更好的分散导致更快溶解的假设。
