Irwan Anastasia W, Berania Jacqueline E, Liu Xueming
a Analytical R&D-Singapore, AbbVie Inc. , The Helios , Biopolis , Singapore.
Pharm Dev Technol. 2016 Mar;21(2):231-8. doi: 10.3109/10837450.2014.991877. Epub 2014 Dec 11.
This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.
本文报道了使用两种结晶聚合物，一种两亲性的普朗尼克®F - 127（PF - 127）和一种亲水性聚乙二醇（PEG6000）作为药物递送载体，通过形成胶束和固体分散体（SD）来改善难溶性药物非诺贝特（FEN）的药物释放。在10%的PF - 127（水溶液）中，由于胶束的形成，FEN的平衡溶解度约为0.6毫克/毫升。相比之下，在10%的PEG6000（水溶液）中，FEN的平衡溶解度仅为0.0037毫克/毫升。PF - 127中负载FEN的胶束通过直接溶解和膜透析制备。两种方法的最高载药量（DL）仅为0.5%。通过溶剂蒸发制备了DL为5 - 80%的FEN在PF - 127和PEG6000中的SD。体外溶出试验表明，胶束和SD均显著提高了FEN的释放速率。当DL高达50%时，FEN在PF - 127中的SD显示出比结晶FEN快得多的释放速率，而当DL不超过20%时，PEG6000的SD在释放速率上有类似的提高。当DL不超过50%时，PF - 127的SD的DSC热谱图在约55 - 57℃处呈现一个单一的相变峰，而当DL不超过35%时，PEG6000中的SD在约61 - 63℃处呈现类似的峰。当PF - 127的SD的DL超过50%且PEG6000的SD的DL超过35%时，DSC热谱图分别显示载体聚合物和FEN的两个熔融峰。FT - IR研究表明，PF - 127与FEN的疏水 - 疏水相互作用比PEG6000更强。PF - 127在其SD中对提高FEN释放速率的更强作用可能是分散和胶束形成共同作用的结果。
