| Self-microemulsion drug delivery system (SMEDDS) is a kind of new drug delivery system. In this study, it has been employed as a vehicle to improve the dissolution and absorption of drug and enhance the bioavailability significantly. Moreover, some excipients are used to absorb the SMEDDS that is proved to be valuable for development of dosage forms.To prepare the SMEDDS and evaluate the in vivo properties within the pre-formulation study, first of all, the IBU is selected as the model drug and the HPLC analytic methods were established. The physiochemical properties of IBU were investigated. The solubility of IBU increases with respect to the increase of pH value. It has the biggest solubility in oil (MCT) that is 91.6 mg·ml-1 and the apparent partition coefficients of IBU in octanol / 0.1 mol·l-1 HCl, octanol / water and octanol / PBS (pH 6.8) are 2.20, 1.48 and 1.16, indicate that IBU was lipophilic.In the formulation study, the MCT is selected as the oil that has the biggest solubility of IBU. With the compatibility study of MCT and surfactants and drawing of the pseudo-ternary phase diagrams of oil / surfactant / cosurfactant, Cremophor RH 40 and PEG 400 are selected as surfactant and cosurfactant respectively. The effect of oil, surfactant, and temperature and drug amount on the IBU SMEDDS is studied. By drawing the ternary phase diagrams at different Km values, the raw Km value is fixed on 1. Uniform Design is utilized and the average particle is selected as the response variables to optimize the SMEDDS formulation (oil 9.6 % and the optimal Km value 1.1). The largest content of IBU in blank SMEDDS is 11 % and the final formulation: IBU 9.0 g, MCT 8.8 g, RH 40 43.4 g, PEG 400 38.8 g. The processing factors that affect the self-microemulsifying time have been studied. The final processes are fixed on the 120 r·min-1 for 20 minutes below 40℃with a magnetic stirrer.The IBU SMEDDS formulation could form oil-in-water ME when diluted with water. The formed ME droplets present sphericity and uniformity under transmission electron microscopy, with the mean particle size of 23 nm, and its Zeta potential was -25.6 mv.The stability of IBU SMEDDS show that there are no obvious change for the drug content, self-microemulsifying time and particle compared with original state when it was stored under accelerated condition and at 4, 40, 60℃and room temperature. In vitro dissolution experiment, the IBU SMEDDS formulation dissolution is no significant in three dissolution media including distilled water, 0.1mol·l-1 hydrochloric acid and the FeSSIF, all more than 95 % in 45 min; however, the commercial tablet is no more than 40 %.The solidification is studied and the SiO2 / lactose (9:1) are used to absorb the IBU SMEDDS to make the powder. The stability of powder is showed by the results of dissolution of IBU from powder, press experiment and stored at room temperature for 6 months. It is proved that the powder indeed improves the stability of IBU SMEDDS and increases the developments of dosage. |
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