Yong Chul Soon, Yang Chae Ha, Rhee Jong-Dal, Lee Beom-Jin, Kim Dong-Chool, Kim Dae-Duk, Kim Chong-Kook, Choi Jun-Shik, Choi Han-Gon
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Int J Pharm. 2004 Jan 9;269(1):169-76. doi: 10.1016/j.ijpharm.2003.09.013.
To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.
为了使用泊洛沙姆和薄荷醇提高难溶性布洛芬在直肠中的生物利用度，研究了薄荷醇和泊洛沙姆188对布洛芬水溶性的影响。随后进行了由泊洛沙姆188和薄荷醇组成的泊洛沙姆凝胶递送布洛芬的溶出度和药代动力学研究。在没有泊洛沙姆的情况下，布洛芬的溶解度增加，直到薄荷醇与布洛芬的比例从0:10增加到4:6，随后在比例高于4:6时溶解度突然下降，这表明四份薄荷醇与六份布洛芬形成了低共熔混合物。在有泊洛沙姆的情况下，相同薄荷醇与布洛芬比例的溶液中布洛芬的溶解度突然增加。薄荷醇/布洛芬比例为1:9且泊洛沙姆188高于15%的泊洛沙姆凝胶显示布洛芬的最大溶解度为1.2mg/ml。薄荷醇提高了布洛芬从泊洛沙姆凝胶中的溶出速率。释放机制表明，不含薄荷醇的泊洛沙姆凝胶中布洛芬的释放速率与时间无关，但含薄荷醇的泊洛沙姆凝胶中的药物可能通过菲克扩散释放。此外，含薄荷醇的泊洛沙姆凝胶（泊洛沙姆/薄荷醇/布洛芬（15%/0.25%/2.5%））给予的布洛芬初始血浆浓度、C(max)和AUC显著高于固体栓剂，表明泊洛沙姆凝胶中的药物在大鼠体内比固体栓剂中的药物吸收更多。因此，含有泊洛沙姆188和薄荷醇的泊洛沙姆凝胶是一种更有效的布洛芬直肠剂型。
