Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions
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The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. The primary surfactant was PEG-8 caprylic/capric glycerides (Labrasol (R)). The cosurfactants were commercially available mixtures of octoxynol-12 and polysorbate 20 without or with the addition of PEG-40 hydrogenated castor oil (Solubilisant gamma (R) 2421 and Solubilisant gamma (R) 2429, respectively). The oil phase of microemulsions was isopropyl myristate. Phase behaviour study of the pseudo-ternary systems Labrasol (R)/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K-m) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. Solubilization of a model drug ibuprofen in concentration common f...or topical application (5%, w/w) was achieved at the water contents below 50% (w/w). Drug free and ibuprofen-loaded microemulsions M1-M6, containing 45% (w/w) of water phase, were prepared and characterized by polarized light microscopy, conductivity, pH, rheological and droplet size measurements. In vitro ibuprofen release kinetics from the microemulsions was investigated using paddle-over-enhancer cell method and compared with the commercial 5% (w/w) ibuprofen hydrogel product (Deep Relief (R), Mentholatum Company Ltd., USA). The investigated microemulsions were isotropic, low viscous Bingham-type liquids with the pH value (4.70-6.61) suitable for topical application. The different efficiency of the tensides mixtures for microemulsion stabilisation was observed, depending on the cosurfactant type and K-m value. Solubilisant gamma (R) 2429 as well as higher K-m (i.e., lower relative content of the cosurfactant) provided higher surfactant/cosurfactant synergism. The drug molecules were predominantly solubilized within the interface film. The amount of drug released from the formulations M3 (10.75%, w/w) and M6 (13.45%, w/w) (K-m 60: 40) was limited in comparison with the reference (22.22%, w/w) and follows the Higuchi model. Microemulsions M2 and M5 (K-m 50: 50) gave zero order drug release pattern and similar to 15% (w/w) ibuprofen released. The release profiles from microemulsions M1 and M4 (K-m 40: 60) did not fit well with the models used for analysis, although the amounts of ibuprofen released (24.47%, w/w) and 17.99% (w/w), respectively) were comparable to that of the reference hydrogel. The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides corresponded to the faster drug release.
Кључне речи:Microemulsions / Surfactant/cosurfactant synergism / Drug solubilization capacity / In vitro release testing (IVRT) / Ibuprofen
Извор:International Journal of Pharmaceutics, 2012, 433, 1-2, 25-33
- Elsevier Science BV, Amsterdam