Vélaz I, Sánchez M, Martín C, Martínez-Ohárriz M C
Dpto. de Química Sección de Química-Fisica, Facultad de Ciencias, Universidad de Navarra, Pamplona, Spain.
Eur J Drug Metab Pharmacokinet. 1998 Apr-Jun;23(2):103-8. doi: 10.1007/BF03189323.
Naproxen is a nonsteroidal anti-inflammatory drug characterized by its low wettability and poor water solubility. Solid dispersions naproxen:PEG 4000 have been prepared in order to improve the solubility and dissolution rate of the drug, since these factors can be the limiting steps for absorption and bioavailability of poorly soluble drugs. X-ray diffraction analysis, infrared spectroscopy and differential scanning calorimetry detected no physico-chemical interaction between the drug and the inert carrier PEG 4000. The phase diagram of the naproxen-PEG 4000 system produced by DSC and hot stage microscopy is reported. The intrinsic dissolution rate of naproxen is calculated. The dissolution kinetics of solid dispersions prepared by the solvent and melt methods are compared with those of free drug and physical mixture. The studies were carried out at 37 degrees C and pH 1.2 according to the dispersed amount method. The dissolution profiles obtained indicate that a significant dissolution enhancement occurs with solid dispersions in comparison with the physical mixture. In addition, the physical mixture showed a dissolution rate higher than the free drug. Dissolution rate constants were determined by fitting the experimental data to the cube root function, to get straight line plots.
萘普生是一种非甾体抗炎药，其特点是润湿性低且水溶性差。制备了萘普生与聚乙二醇4000的固体分散体，以提高药物的溶解度和溶出速率，因为这些因素可能是难溶性药物吸收和生物利用度的限制步骤。X射线衍射分析、红外光谱和差示扫描量热法未检测到药物与惰性载体聚乙二醇4000之间的物理化学相互作用。报道了通过差示扫描量热法和热台显微镜得到的萘普生-聚乙二醇4000体系的相图。计算了萘普生的固有溶出速率。将溶剂法和熔融法制备的固体分散体的溶出动力学与游离药物和物理混合物的溶出动力学进行了比较。根据分散量法在37℃和pH 1.2条件下进行研究。得到的溶出曲线表明，与物理混合物相比，固体分散体的溶出显著增强。此外，物理混合物的溶出速率高于游离药物。通过将实验数据拟合到立方根函数来确定溶出速率常数，以得到直线图。
