Yong Chul Soon, Jung Se Hyun, Rhee Jong-Dal, Choi Han-Gon, Lee Beom-Jin, Kim Dong-Chool, Choi Young Wook, Kim Chong-Kook
College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
Drug Deliv. 2003 Jul-Sep;10(3):179-83. doi: 10.1080/713840406.
To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were 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 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.
为了用泊洛沙姆和薄荷醇提高难溶性布洛芬的溶解度和体外溶出度,研究了薄荷醇和泊洛沙姆188对布洛芬在水中溶解度的影响。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时溶解度急剧下降,这表明4份布洛芬与6份薄荷醇形成了低共熔混合物。在有泊洛沙姆188存在的情况下,相同薄荷醇与布洛芬比例的溶液中布洛芬的溶解度急剧增加。此外,比例为4:6的溶液中布洛芬的溶解度分别比没有泊洛沙姆和没有薄荷醇的溶液增加了2.5倍以上和6倍以上。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。溶出机制表明,没有薄荷醇的泊洛沙姆凝胶中布洛芬的溶出速率与时间无关,但药物可能通过菲克扩散从含有薄荷醇的泊洛沙姆凝胶中溶解出来。因此,使用与薄荷醇的低共熔混合物开发的泊洛沙姆凝胶提高了药物的溶解度和溶出度,是负载布洛芬的透皮和直肠给药系统的潜在候选者。