Formulation of parenteral microemulsion containing itraconazole.
The aim of this study was to develop an aqueous parenteral formulation containing itraconazole (ITZ) using an o/w microemulsion system. A mixture of benzyl alcohol and medium chain triglyceride (3/1) was chosen as the oil phase. Pseudoternary phase diagrams of the microemulsion formations were constructed in order to determine the optimum ratio of oils, the concentration range of surfactant and cosurfactant and the optimum ratio between them. Consequently, the suitability of the chosen microemulsion system as a parenteral formulation was evaluated using droplet size analysis and hemolysis tests. Among the surfactants and cosurfactants screened, a mixture of polyoxyethylene (50) hydrogenated castor oil and ethanol (3/1) showed the largest o/w microemulsion region in the phase diagram. The average droplet size of the microemulsions was < 150 nm, and the hemolysis test showed this formulation to be nontoxic to red blood cells. The pharmacokinetic profiles of the ITZ-microemulsion for itraconazole and its major metabolite, hydroxyitraconazole, were compared with those of a PEG 400 solution and cyclodextrin formulations in rats. Overall, these results highlight the potential of an ITZ-microemulsion formulation for the parenteral route.
Rhee
Yun-Seok
YS
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Park
Chun-Woong
CW
Nam
Tae-Young
TY
Shin
Yoon-Sub
YS
Chi
Sang-Cheol
SC
Park
Eun-Seok
ES
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D019905:Benzyl Alcohol / Q000737:chemistry; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry* / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D007275:Injections, Intravenous; D017964:Itraconazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
D000935:Antifungal Agents; D004655:Emulsions; D005079:Excipients; D012997:Solvents; D013501:Surface-Active Agents; D014280:Triglycerides; D047392:beta-Cyclodextrins; D014867:Water; C084794:hydroxyitraconazole; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017964:Itraconazole; D000431:Ethanol; D011092:Polyethylene Glycols; C023040:polyethoxylated castor oil; D002368:Castor Oil; D019905:Benzyl Alcohol