title: Preparation and characterization of microemulsion of cilostazol for enhancement of oral bioavailability.
abstract: Cilostazol is a promising drug for antiplatelet combination therapy that is very important for treatment for various cardiovascular disorders. However, oral delivery of this drug is greatly impeded by the poor solubility in aqueous solutions. The aim of this study was to develop microemulsion (ME) delivery system capable of improving the drug bioavailability. In this study, Capmul MCM C8 (glycerol monocaprylate) based MEs containing Tween 20(polysorbate 20) and/or Labrafil M 1944(poly oxyglycerides) as surfactant(S) and Transcutol P(diethyl glycol monoethyl ether) as cosurfactant(CoS) were studied as potential delivery systems of cilostazol. A number of such systems were prepared containing different S:CoS ratios(1:1, 2:1 and 3:1) based on phase diagrams. Loading of cilostazol was selected as per solubilization capacity and was characterized for pH, viscosity, conductivity, particle size, zeta potential and % transmittance. The MEs systems were further investigated for chemical stability, diffusion and bioavailability. Cilostazol displayed high solubility in microemulsions with particle size up to 70 nm. It was also stable at ambient temperature up to 6 months without significant change in particle size, zeta potential, and % transmittance. Dilution up to 100 fold with aqueous medium observed a visible cloudiness having a particle size up to 104 nm. The in vitro release, and ex vivo intraduodenal diffusion, and in vivo study indicated the capacity of developed ME to improve the bioavailability (1.43 fold) via oral route administration when compared with commercially available tablets (Pletoz-50).
authors.forename: Samir G
authors.initials: SG
authors.lastname: Patel
authors.forename: Sadhana J
authors.initials: SJ
authors.lastname: Rajput
authors.forename: Anastasia
authors.initials: A
authors.lastname: Groshev
authors.affiliation: Department of Pharmaceutical Sciences, University of South Florida College of Pharmacy, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612-4749, USA. vsutariy@health.usf.edu.
authors.forename: Vijaykumar B
authors.initials: VB
authors.lastname: Sutariya
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D000077407:Cilostazol; D016503:Drug Delivery Systems; D004355:Drug Stability; D004386:Duodenum / Q000378:metabolism; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006207:Half-Life; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010316:Particle Size; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D004655:Emulsions; D005079:Excipients; D058987:Phosphodiesterase 3 Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol