Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent.
Gelucire 44/14 is a surface-active excipient that can solubilize poorly soluble drugs. We investigated its solubilization behavior when coexisting with dimethylacetoamide (DMA) or dimethylsulfoxide (DMSO), both of which are also expected to enhance drug solubility. Gelucire was confirmed to form micelles by surface tension and fluorescence measurements both in water and water/cosolvent mixtures. Light-scattering measurements revealed that DMA and DMSO affect the micellar morphology in a different manner. DMA helped form large structures by being entrapped in the hydrophobic region of the micelles and/or inducing the aggregation. DMSO was likely to be anchored to the interfacial layer and did not induce micelle growth. Two model drugs, phenytoin and indomethacin, were employed to observe the solubilization behavior of poorly soluble drugs in Gelucire/cosolvent mixtures. The solubility of these drugs in the mixtures could be explained very well by using the new solubility model introduced in this article. Addition of cosolvents to the Gelucire solution did not enhance the solubility very much, and thus the combined use of cosolvents with Gelucire offered only little advantage from the viewpoint of solubility.
Kawakami
Kohsaku
K
Developmental Research Laboratories, Shionogi & Co., Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. kohsaku.kawakami@shionogi.com
Miyoshi
Kyoko
K
Ida
Yasuo
Y
D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D012997:Solvents / Q000737:chemistry* / Q000493:pharmacokinetics; D013500:Surface Tension / Q000187:drug effects
D004338:Drug Combinations; D012997:Solvents; C104509:gelucire 44-14; D011092:Polyethylene Glycols