Al-Obaidi Hisham, Lawrence M Jayne, Buckton Graham
The School of Pharmacy, University of Reading, Reading, UK.
Institute of Pharmaceutical Science, King's College London, London, UK.
J Pharm Pharmacol. 2016 Nov;68(11):1373-1383. doi: 10.1111/jphp.12645. Epub 2016 Oct 2.
To understand the impact of ionic and non-ionic surfactants on the dissolution and stability properties of amorphous polymeric dispersions using griseofulvin (GF) as a model for poorly soluble drugs.
Solid dispersions of the poorly water-soluble drug, griseofulvin (GF) and the polymers, poly(vinylpyrrolidone) (PVP) and poly(2-hydroxypropyl methacrylate) (PHPMA), have been prepared by spray drying and bead milling and the effect of the ionic and non-ionic surfactants, namely sodium dodecyl sulphate (SDS) and Tween-80, on the physico-chemical properties of the solid dispersions studied.
The X-ray powder diffraction data and hot-stage microscopy showed a fast re-crystallisation of GF. While dynamic vapour sorption (DVS) measurements indicated an increased water uptake, slow dissolution rates were observed for the solid dispersions incorporating surfactants. The order by which surfactants free dispersions were prepared seemed critical as indicated by DVS and thermal analysis. Dispersions prepared by milling with SDS showed significantly better stability than spray-dried dispersions (drug remained amorphous for more than 6 months) as well as improved dissolution profile.
We suggest that surfactants can hinder the dissolution by promoting aggregation of polymeric chains, however that effect depends mainly on how the particles were prepared.
以灰黄霉素（GF）作为难溶性药物的模型，了解离子型和非离子型表面活性剂对无定形聚合物分散体的溶解和稳定性的影响。
通过喷雾干燥和珠磨法制备了难溶性药物灰黄霉素（GF）与聚合物聚乙烯吡咯烷酮（PVP）和聚甲基丙烯酸2-羟丙酯（PHPMA）的固体分散体，并研究了离子型和非离子型表面活性剂，即十二烷基硫酸钠（SDS）和吐温80对固体分散体物理化学性质的影响。
X射线粉末衍射数据和热台显微镜显示GF快速重结晶。虽然动态蒸汽吸附（DVS）测量表明吸水量增加，但含表面活性剂的固体分散体的溶解速率较慢。DVS和热分析表明，制备表面活性剂游离分散体的顺序似乎至关重要。用SDS研磨制备的分散体显示出比喷雾干燥分散体显著更好的稳定性（药物在6个月以上保持无定形）以及改善的溶解曲线。
我们认为表面活性剂可通过促进聚合物链的聚集来阻碍溶解，然而这种影响主要取决于颗粒的制备方式。
