Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Arch Pharm Res. 2010 Jun;33(6):901-10. doi: 10.1007/s12272-010-0613-7. Epub 2010 Jul 6.
Solid dispersions of artemether (ARM), a poorly soluble drug, were prepared using polyvinylpyrrolidone (PVPK25, MW 25000) and polyethyleneglycol (PEG4000, MW 4000) as excipients. These dispersions were studied by physical mixture, freeze-drying, and melting methods. They were characterized by X-ray diffraction pattern, fourier transform infrared spectrophotometry, differential scanning calorimetery, and dissolution studies. X-ray diffraction pattern revealed the complete crystalline nature of artemether, whereas physical mixtures, melt mixtures (MM), and freeze-dried solid dispersions (FDSD) of ARM-PVP and ARM-PEG showed reduced peak intensities with increased PVP/PEG content. PEG showed lower decreases in intensity than PVP preparations. Differential scanning calorimetery also confirmed this finding by showing either a small or absent endotherm. Red shifts in O-H stretching vibrations of ARM were higher in the MM of ARM-PVP than its FDSD as exhibited by fourier transform infrared spectrophotometry. The carbonyl peak of PEG was blue shifted in MM and FDSD, whereas the C=O peak of PVP was red shifted in FDSD and MM, indicating different H-bonding by PEG and PVP with ARM. The rate of dissolution (phosphate buffer at pH 4.5) was improved up to 4-fold in MM and FDSD compared to artemether, and up to 50% compared to physical mixtures. The preparation of solid dispersions influenced the rate of dissolution at various drug-carrier ratios, i.e., the dissolution order of 1:1-1:4 ratio was MM > FDSD; FDSD > MM at 1:6-1:8 ratios of both ARM-PVP and ARM-PEG; and FDSD of ARM-PEG > FDSD of ARM-PVP > MM of ARM-PEG > MM of ARM-PVP at a 1:10 ratio.
固体分散体的青蒿素(ARM ),一种溶解度差的药物,是用聚乙烯吡咯烷酮(PVPK25 ,分子量为 25000 )和聚乙二醇(PEG4000 ,分子量为 4000 )作为赋形剂制备的。这些分散体通过物理混合物,冷冻干燥和熔融方法进行研究。它们的特征在于 X 射线衍射图,傅里叶变换红外分光光度法,差示扫描量热法和溶解研究。X 射线衍射图显示青蒿素完全具有结晶性质,而物理混合物,熔融混合物( MM )和冷冻干燥固体分散体( FDSD )的 ARM-PVP 和 ARM-PEG 的峰强度降低,随着 PVP/PEG 含量的增加而降低。PEG 显示出比 PVP 制剂更低的强度降低。差示扫描量热法也通过显示小的或不存在的吸热峰来证实这一发现。傅里叶变换红外分光光度法显示,ARM-PVP 的 MM 中 ARM 的 O-H 伸缩振动的红移高于其 FDSD 。MM 和 FDSD 中 PEG 的羰基峰发生蓝移,而 FDSD 和 MM 中 PVP 的 C=O 峰发生红移,表明 PEG 和 PVP 与 ARM 具有不同的氢键。与青蒿素相比,在 MM 和 FDSD 中,溶解速率( pH4.5 的磷酸盐缓冲液)提高了 4 倍,与物理混合物相比提高了 50 %。固体分散体的制备影响了在各种药物载体比下的溶解速率,即 1:1-1:4 比例的溶解顺序为 MM > FDSD ; 1:6-1:8 比例的 ARM-PVP 和 ARM-PEG 的 FDSD > MM ;而在 1:10 比例下,ARM-PEG 的 FDSD > ARM-PVP 的 FDSD > ARM-PEG 的 MM > ARM-PVP 的 MM 。