title: Preparation, characterization and optimization of probucol self-emulsified drug delivery system to enhance solubility and dissolution.
abstract: The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution and better chance for oral absorption. The methods included determination of the solubility of probucol in different oils, surfactants and co-surfactants using saturation solubility method and HPLC for drug analysis. The ingredients showing high drug solubility were used to prepare PBSEDDS after being tested for physical and chemical compatibility with the drug using DSC and FTIR. The prepared formulations were evaluated for droplet size, turbidity, spontaneity of emulsification and dissolution in water. Optimization was performed using a three-factor, three-level Box-Behnken experimental design. The results showed high drug solubility and compatibility with soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant ratio showed large influence on the characteristics of PBSEDDS. Several fold improvement of drug dissolution was observed compared to drug solution in soybean oil alone. Optimization study showed that observed and predicted values of cumulative percent drug dissolution after 60 min were in reasonable agreement. The experimental design applied helped in understanding the effects and the interaction effects between the independent factors. The prepared PBSEDDS may have the potential to enhance the therapeutic bioavailability of probucol.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait. abdel@hsc.edu.kw
authors.forename: A
authors.initials: A
authors.lastname: Zaghloul
authors.forename: I
authors.initials: I
authors.lastname: Khattab
authors.forename: A
authors.initials: A
authors.lastname: Nada
authors.forename: S
authors.initials: S
authors.lastname: Al-Saidan
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients; D007202:Indicators and Reagents; D015233:Models, Statistical; D009391:Nephelometry and Turbidimetry; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011341:Probucol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents; D014867:Water / Q000737:chemistry
chemical_list: D000924:Anticholesteremic Agents; D004655:Emulsions; D005079:Excipients; D007202:Indicators and Reagents; D009821:Oils; D012996:Solutions; D013501:Surface-Active Agents; D014867:Water; D011341:Probucol