Fujimori Miki, Kadota Kazunori, Tozuka Yuichi
Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
J Pharm Sci. 2017 Apr;106(4):1117-1123. doi: 10.1016/j.xphs.2016.12.024. Epub 2017 Jan 3.
Transglycosylated stevia (stevia-G) can effectively improve the dissolution and bioavailability of poorly water-soluble drugs. Furthermore, addition of an ionic surfactant to stevia-G solution has been shown to enhance the dissolution effect of stevia-G on flurbiprofen. Herein, 4 surfactants, namely sodium dodecyl sulfate, sodium N-dodecanoylsarcosinate, sodium monododecyl phosphate, and lauryltrimethylammonium chloride (LTAC) were screened to investigate their synergistic effect with stevia-G in enhancing the solubility of mefenamic acid (MFA). The ternary formulation containing LTAC produced the highest increase in solubility, whereas the binary MFA/LTAC formulation did not increase the solubility of MFA. Surface tension was evaluated to analyze the interaction between stevia-G and each ionic surfactant, wherein the Rubingh model was applied to predict mixed micelle formation between stevia-G and LTAC. Interaction parameters calculated by the Rubingh model reflected mixed micelle formation between stevia-G and LTAC relative to the self-interactions of the 2 individual surfactants. All interaction parameters in this system showed negative values, indicating a favorable interaction (e.g., hydrogen bond or electrostatic and dipole) between binary components in the mixed micelles. Spray-dried particles of ternary formulations (MFA/stevia-G/LTAC) were prepared to evaluate the dissolution profile and physicochemical properties. Dissolution profiling showed that the concentration of MFA released from spray-dried particles was significantly higher than untreated MFA.
转糖基甜菊糖苷（甜菊糖苷-G）能有效提高难溶性药物的溶出度和生物利用度。此外，向甜菊糖苷-G溶液中添加离子型表面活性剂已被证明可增强甜菊糖苷-G对氟比洛芬的溶出效果。在此，筛选了4种表面活性剂，即十二烷基硫酸钠、N-十二酰肌氨酸钠、单十二烷基磷酸钠和十二烷基三甲基氯化铵（LTAC），以研究它们与甜菊糖苷-G在提高甲芬那酸（MFA）溶解度方面的协同作用。含LTAC的三元制剂溶解度增加最高，而二元MFA/LTAC制剂并未提高MFA的溶解度。评估表面张力以分析甜菊糖苷-G与每种离子型表面活性剂之间的相互作用，其中应用鲁宾模型预测甜菊糖苷-G与LTAC之间混合胶束的形成。通过鲁宾模型计算的相互作用参数反映了甜菊糖苷-G与LTAC之间相对于两种单一表面活性剂自身相互作用的混合胶束形成情况。该体系中所有相互作用参数均为负值，表明混合胶束中二元组分之间存在良好的相互作用（如氢键或静电及偶极作用）。制备了三元制剂（MFA/甜菊糖苷-G/LTAC）的喷雾干燥颗粒以评估其溶出曲线和理化性质。溶出曲线表明，喷雾干燥颗粒释放的MFA浓度显著高于未处理的MFA。
