Pharmacy and Pharmaceutical Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Int J Pharm. 2013 Nov 30;457(1):197-205. doi: 10.1016/j.ijpharm.2013.09.027. Epub 2013 Sep 29.
Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin.
采用聚维酮（PVP）和聚乙二醇（PEG）聚合物共混物制备了青蒿素的固体分散体，旨在提高青蒿素的溶解度和体外透皮渗透。通过分子动力学（MD）模拟、差示扫描量热法（DSC）、X 射线衍射（XRD）和傅里叶变换红外光谱（FT-IR）对制剂进行了表征。在两种溶剂中测定了青蒿素的溶解度：去离子水和磷酸盐缓冲盐水（PBS；pH7.4），同时使用兔皮作为模型膜进行了体外药物渗透研究。MD 模拟显示药物与聚合物之间具有混溶性。DSC 证实了药物在聚合物共混物中的分子分散性。XRD 和 FT-IR 分别证实了青蒿素结晶度相对于聚合物含量的降低以及药物与聚合物之间不存在特定的相互作用。与纯药物的饱和溶液相比，青蒿素固体分散体的溶解度显著提高，青蒿素的渗透也得到了提高。该研究表明，青蒿素的高能固体形式可能能够实现青蒿素的经皮给药。
