Department of Pharmaceutical Science, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Colloids Surf B Biointerfaces. 2011 Jun 1;84(2):508-14. doi: 10.1016/j.colsurfb.2011.02.006. Epub 2011 Feb 25.
The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.
本研究旨在开发一种适合硫酸庆大霉素（GS）的制剂，以实现药物的持续释放。因此，将该药物载入聚（D，L-丙交酯-共-乙交酯）（PLGA）和聚（乳酸-共-羟甲基乙二醇酸）（PLHMGA）微球中。考察了各种制剂参数（乙醇、表面活性剂、外相渗透压、聚合物类型和浓度）对颗粒特性（粒径、载药量和释放）的影响。采用复乳蒸发技术制备GS 载药微球。结果表明，乙醇和表面活性剂对药物载药量（约 4-10%）均无有利影响。然而，外相缓冲液浓度（即渗透压）的增加会导致 GS 载药量的显著增加（从 10%增加到 28%）。此外，DCM 中 PLGA 浓度从 10%增加到 15/20%会使药物载药量增加 4 倍。本研究中确定的最佳制剂的载药效率约为 70%，得到载药量为 6%（w/w）的 PLGA 微球。这些颗粒表现出药物的突释，这取决于其孔隙率，随后是 35 天几乎没有药物释放的阶段。然后，药物可能由于微球的降解而缓慢释放约 25 天。GS 在 PLHMGA 中的载药效率与 PLGA 微球无显著差异（64%）。GS 从 PLHMGA 微球中的释放速度快于 PLGA，因为 PLHMGA 的降解速度快于 PLGA。本研究表明，通过将该药物载入可生物降解的脂肪族聚酯微球中，可以获得庆大霉素的长效释放。
