PURPOSE: This study evaluated the effects of combined use of two nonionic surfactants on the characteristics (i.e., appearance, emulsification time, and particle size) of oil-in-water microemulsions generated from flurbiprofen-loaded preconcentrates. METHODS: Three phase diagrams were constructed using Capmul PG8 (propylene glycol monocaprylate) as the oil, Tween 20 (polysorbate 20) and/or Cremophor EL (polyoxyl 35 castor oil) as surfactants. A number of preconcentrates were selected based on phase diagrams: O20T80 (20% Capmul PG8, 80% Tween 20), O20C80 (20% Capmul PG8, 80% Cremophor EL), O20T40C40 (20% Capmul PG8, 40% Tween 20, 40% Cremophor EL). Flurbiprofen loading in preconcentrates was tested at 0%, 1%, 2.5%, and 5% (w/w). The resulting mixtures of these preconcentrates upon dilution 100-fold with aqueous medium were characterized by visual and microscopic observation, HPLC and photon correlation spectroscopy. RESULTS: (a) For preconcentrates using single surfactant, either O20T80 or O20C80, the dilution generated emulsions with visible cloudiness. The particle size increased as the drug loading increased; (b) for preconcentrates using two surfactants O20T40C40, the dilution generated clear microemulsions with small particle sizes (10-11nm), and the increased drug loading seemed to have little effect on the particle size. The microemulsions from preconcentrate O20T40C40 was also found to be stable at ambient temperature over 20 days without significant change in particle size at different drug loadings. Dilution with different aqueous medium, either water, or simulated gastric fluid or simulated intestinal fluid, also did not change the particle sizes of the microemulsions. CONCLUSIONS: The combined use of surfactants in preconcentrate showed the promise in generating desired self-emulsifying microemulsions with small particle size, increased drug loading, and improved physical stability. This will have significant implications in future dosage development for poorly water-soluble drugs in using self-emulsifying microemulsions drug delivery system (SMEDDS).
PURPOSE: This study evaluated the effects of combined use of two nonionic surfactants on the characteristics (i.e., appearance, emulsification time, and particle size) of oil-in-water microemulsions generated from flurbiprofen-loaded preconcentrates. METHODS: Three phase diagrams were constructed using CapmulPG8 (propylene glycol monocaprylate) as the oil, Tween 20 (polysorbate 20) and/or Cremophor EL (polyoxyl 35 castor oil) as surfactants. A number of preconcentrates were selected based on phase diagrams: O20T80 (20% CapmulPG8, 80% Tween 20), O20C80 (20% CapmulPG8, 80% Cremophor EL), O20T40C40 (20% CapmulPG8, 40% Tween 20, 40% Cremophor EL). Flurbiprofen loading in preconcentrates was tested at 0%, 1%, 2.5%, and 5% (w/w). The resulting mixtures of these preconcentrates upon dilution 100-fold with aqueous medium were characterized by visual and microscopic observation, HPLC and photon correlation spectroscopy. RESULTS: (a) For preconcentrates using single surfactant, either O20T80 or O20C80, the dilution generated emulsions with visible cloudiness. The particle size increased as the drug loading increased; (b) for preconcentrates using two surfactants O20T40C40, the dilution generated clear microemulsions with small particle sizes (10-11nm), and the increased drug loading seemed to have little effect on the particle size. The microemulsions from preconcentrate O20T40C40 was also found to be stable at ambient temperature over 20 days without significant change in particle size at different drug loadings. Dilution with different aqueous medium, either water, or simulated gastric fluid or simulated intestinal fluid, also did not change the particle sizes of the microemulsions. CONCLUSIONS: The combined use of surfactants in preconcentrate showed the promise in generating desired self-emulsifying microemulsions with small particle size, increased drug loading, and improved physical stability. This will have significant implications in future dosage development for poorly water-soluble drugs in using self-emulsifying microemulsions drug delivery system (SMEDDS).
Authors: Jean F Cuiné; William N Charman; Colin W Pouton; Glenn A Edwards; Christopher J H Porter Journal: Pharm Res Date: 2007-02-15 Impact factor: 4.200
Authors: Jia Xi; Qi Chang; Chak K Chan; Zhao Yu Meng; Geng Nan Wang; Jia Bei Sun; Yi Tao Wang; Henry H Y Tong; Ying Zheng Journal: AAPS PharmSciTech Date: 2009-02-18 Impact factor: 3.246