Mura P, Moyano J R, González-Rodríguez M L, Rabasco-Alvaréz A M, Cirri M, Maestrelli F
Dipartimento di Scienze Farmaceutiche, Polo Scientifico, Sesto Fiorentino, Firenze, Italia.
Drug Dev Ind Pharm. 2005 May;31(4-5):425-34. doi: 10.1080/03639040500214621.
The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has been investigated. Physicochemical and morphological properties of the various solid systems were determined by differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction analysis, and scanning electron microscopy. The results from dissolution studies, performed according to the USP 24 basket method, indicated that all ternary dispersed systems were significantly (p < 0.001) more efficacious than the corresponding binary ones, by virtue of the additive wetting and solubilizing effect due to the presence of the surfactant. The relative effectiveness of the incorporated surfactant was in the same order as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the solid dispersion preparation method, coevaporated products always gave better results than the corresponding cofused ones; however, this effect was statistically significant (p < 0.001) only in the initial phase of the dissolution process. The most effective solid dispersion was the 10-80-10 w/w drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary coevaporate) and dissolution of about 100% drug after 30 min (in comparison with > 120 min for the binary coevaporate).
研究了掺入阴离子型表面活性剂（十二烷基硫酸钠[SDS]或二辛基磺基琥珀酸钠[DSS]）或非离子型表面活性剂（吐温60[TW60]）对酮洛芬在聚乙二醇15000（PEG）中固体分散体性质的影响。通过差示扫描量热法、热台显微镜、X射线粉末衍射分析和扫描电子显微镜测定了各种固体体系的物理化学和形态学性质。根据美国药典24篮法进行的溶出度研究结果表明，由于表面活性剂的存在具有增湿和增溶的叠加效应，所有三元分散体系均比相应的二元体系显著更有效（p<0.001）。掺入表面活性剂的相对有效性与相溶解度研究中的顺序相同（即SDS>DSS> TW60）。关于固体分散体制备方法，共蒸发产物的效果总是优于相应的共熔产物；然而，这种效应仅在溶出过程的初始阶段具有统计学意义（p<0.001）。最有效的固体分散体是10-80-10 w/w药物-PEG-SDS三元共蒸发物，其仅在6分钟后就能使50%的药物溶解（相比之下，单独药物>120分钟，二元共蒸发物17分钟），30分钟后约100%的药物溶解（相比之下，二元共蒸发物>120分钟）。
