Characterization and evaluation of solid self-microemulsifying drug delivery systems with porous carriers as systems for improved carbamazepine release


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Abstract

The purpose of this study was to investigate solid self-microemulsifying drug delivery system (SSMEDDS), as potential delivery system for poorly water soluble drug carbamazepine (CBZ). Self-microemulsifying drug delivery system (SMEDDS) was formulated using the surfactant polyoxyethylene 20 sorbitan monooleate [Polysorbate 80] (S), the cosurfactant PEG-40 hydrogenated castor oil [Cremophor® RH40] (C) and the oil caprylic/capric triglycerides [Mygliol® 812] (O). Four different adsorbents with high specific surface area were used: Neusilin® UFL2, Neusilin® FL2 (magnesium aluminometasilicate), Sylysia® 320 and Sylysia® 350 (porous silica). Microemulsion area at the surfactant to cosurfactant ratio (Km) 1:1 was evaluated and for further investigation SMEDDS with SC/O ratio 8:2 was selected. Solubilization capacity of selected SMEDDS for CBZ was 33.771 ± 0.041 mg/ml. Rheological measurements of unloaded and CBZ-loaded SMEDDS at water content varied from 10 to 60% (w/w) were conducted. It has been found that CBZ has great influence on rheological behaviour of investigated system upon water dilution. Photon correlation spectroscopy has shown the ability of CBZ-loaded SMEDDS to produce microemulsion droplet size. SSMEDDS improved release rate of CBZ, but the type of adsorbent significantly affects release rate of CBZ. For SSMEDDS with different magnesium aluminometasilicate adsorbents, release rate of CBZ decreased with increasing specific surface area due to entrapment of liquid SMEDDS inside the pores and its gradual exposure to dissolution medium. With porous silica adsorbents no difference in release rate was found in comparison to physical mixtures. In physical mixtures at 12.5% (w/w) CBZ content, presence of amorphous CBZ led to high dissolution rate.

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