title: Development and characterization of self-microemulsifying drug delivery system of tacrolimus for intravenous administration.
abstract: Tacrolimus (FK 506), a poorly soluble immunosuppressant is currently formulated in nonaqueous vehicle containing hydrogenated castor oil derivative for intravenous administration. Hydrogenated castor oil derivatives are associated with acute anaphylactic reactions. This proposes to overcome the problems of poor aqueous solubility of the drug and the toxicity associated with currently used excipients by the development of a new parenterally acceptable formulation using self-microemulsifying drug delivery system (SMEDDS). Solubility of FK 506 in various oils, surfactants, and cosurfactants was determined to identify SMEDDS components. Phase diagrams were constructed at different ratios of surfactants:cosurfactant (K(m)) to determine microemulsion existence area. Influence of oily phase content, K(m), aqueous phase composition, dilution, and incorporation of drug on mean globule size of microemulsions was studied. SMEDDSs were developed using ethyl oleate as oily phase and Solutol HS 15 as surfactant. Glycofurol was used successfully as a cosurfactant. Developed SMEDDS could solubilize 0.8% (wt/wt) FK 506 and on addition to aqueous phase could form spontaneous microemulsion with mean globule size < 30 nm. The resulting microemulsion was iso-osmotic, did not show any phase separation or drug precipitation even after 24 h, and exhibited negligible hemolytic potential to red blood cells.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz, Mumbai, India.
authors.forename: Vivek Baban
authors.initials: VB
authors.lastname: Borhade
authors.forename: Hema Ajit
authors.initials: HA
authors.lastname: Nair
authors.forename: Darshana Deepak
authors.initials: DD
authors.lastname: Hegde
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D004339:Drug Compounding; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D005615:Freezing; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D051379:Mice; D009821:Oils / Q000737:chemistry; D009997:Osmotic Pressure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013242:Sterilization; D013501:Surface-Active Agents / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D009821:Oils; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D016559:Tacrolimus; C018557:glycofurol