Formulation and Characterization of Toremifene Self-Microemulsifying Drug Delivery System for Enhancement of Oral Bioavailability.

The limited water solubility and dissolution of drugs classified under the Biopharmaceutics Classification System (BCS) class II category provide constraints on their oral bioavailability. In the present study, a self-micro emulsifying drug delivery system (SMEDDS) was employed to enhance the aqueous solubility and oral bioavailability of toremifene, which belongs to the Biopharmaceutics Classification System (BCS) class II category. The selection of Oleic Acid, Transcutol-P, and Span 20 as the oil, surfactant combination, and cosurfactant, respectively, was based on the solubility. The optimal composition (Oleic Acid / Transcutol-P / Span 20 in a volume ratio) for toremifene, which exhibits a small droplet size (132.1 nm) and consistent microemulsification was determined by the use of pseudo-ternary phase diagrams. Differential scanning calorimetry and powder X-ray diffraction were employed to identify the loss of crystallinity in lyophilized toremifene. The results indicated that toremifene existed in a molecularly dissolved or amorphous state inside the SMEDDS formulation. The saturation solubility and dissolving rate of toremifene -SMEDDS exhibited significant enhancements compared to toremifene powder when tested in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8). The female rats exhibited a 1.94-fold increase in the area under the curve and a 1.80-fold increase in the highest plasma concentration following the oral administration of toremifene-SMEDDS compared to the oral administration of the toremifene dispersion. In summary, the findings of our study suggest that self-microemulsifying drug delivery systems (SMEDDS) have promise as an oral formulation for enhancing the therapeutic efficacy of toremifene. [ABSTRACT FROM AUTHOR]