School of Pharmacy, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK.
Pharm Res. 2013 Jan;30(1):290-302. doi: 10.1007/s11095-012-0873-7. Epub 2012 Sep 15.
To evaluate the role of polymer-surfactant interactions in drug solubilisation/stabilisation during the dissolution of spray-dried solid dispersions and their potential impact on in vivo drug solubilisation and absorption.
Dissolution/precipitation tests were performed on spray-dried HPMC-Etravirine solid dispersions to demonstrate the impact of different surfactants on the in vitro performance of the solid dispersions. Interactions between HPMC and bio-relevant and model anionic surfactants (bile salts and SDS respectively) were further characterised using surface tension measurements, fluorescence spectroscopy, DLS and SANS.
Fast and complete dissolution was observed in media containing anionic surfactants with no drug recrystallisation within 4 h. The CMCs of bile salts and SDS were dramatically reduced to lower CACs in the presence of HPMC and Etravirine. The maximum increases of the apparent solubility of Etravirine were with the presence of HPMC and SDS/bile salts. The SANS and DLS results indicated the formation of HPMC-SDS/bile salts complexes which encapsulated/solubilised the drug.
This study has demonstrated the impact HPMC-anionic surfactant interactions have during the dissolution of non-ionic hydrophilic polymer based solid dispersions and has highlighted the potential relevance of this to a fuller understanding of drug solubilisation/stabilisation in vivo.
评估聚合物-表面活性剂相互作用在喷雾干燥固体分散体溶解过程中对药物增溶/稳定的作用，及其对体内药物增溶和吸收的潜在影响。
对 HPMC-依曲韦林喷雾干燥固体分散体进行溶解/沉淀试验，以证明不同表面活性剂对固体分散体体外性能的影响。进一步采用表面张力测量、荧光光谱法、DLS 和 SANS 对 HPMC 与生物相关和模型阴离子表面活性剂（分别为胆汁盐和 SDS）之间的相互作用进行了表征。
在含有阴离子表面活性剂的介质中观察到快速且完全的溶解，4 小时内无药物重结晶。在 HPMC 和依曲韦林存在的情况下，胆汁盐和 SDS 的 CMC 急剧降低至更低的 CAC。依曲韦林的表观溶解度最大增加是在存在 HPMC 和 SDS/胆汁盐的情况下。SANS 和 DLS 结果表明形成了 HPMC-SDS/胆汁盐复合物，该复合物包裹/增溶了药物。
本研究证明了 HPMC-阴离子表面活性剂相互作用在非离子亲水性聚合物基固体分散体溶解过程中的影响，并强调了这对更全面理解体内药物增溶/稳定的潜在相关性。
