title: Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.
abstract: Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires , Buenos Aires , Argentina and.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Monteagudo
authors.forename: Mariana
authors.initials: M
authors.lastname: Langenheim
authors.forename: Claudia
authors.initials: C
authors.lastname: Salerno
authors.forename: Fabián
authors.initials: F
authors.lastname: Buontempo
authors.forename: Carlos
authors.initials: C
authors.lastname: Bregni
authors.forename: Adriana
authors.initials: A
authors.lastname: Carlucci
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009821:Oils / Q000737:chemistry; D010634:Phenobarbital / Q000008:administration & dosage* / Q000737:chemistry; D012212:Rheology; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013649:Taste
chemical_list: D000927:Anticonvulsants; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D009821:Oils; D013501:Surface-Active Agents; D010634:Phenobarbital
keywords: Biopharmaceutical advantages; SEDDS; chemical degradation; electronic tongue; microemulsion