Molecular modelling and multisimplex optimization of tocotrienol-rich Self Emulsified Drug Delivery Systems

作者：Alayoubi Alaadin; Satyanarayanajois Seetharama D; Sylvester Paul W; Nazzal Sami^*

来源：International Journal of Pharmaceutics, 2012, 426(1-2): 153-161.

DOI：10.1016/j.ijpharm.2012.01.049

• Surfactants
• Nanoemulsions
• Physical characterization
• Tocotrienol
• Multisimplex (R)
• SEDDS

The objective of this study was to optimize a novel tocotrienol (TRF)-rich Self Emulsified Drug Delivery System (SEDDS). In the first part, an unusual phenomenon was investigated. It was observed that by substituting Tween (R) 80 with Cremophor (R) EL in the SEDDS it was possible to emulsify > 55% TRF (by weight of the formulation) into submicron (<200 nm) emulsion. With Tween (R), only 17.5% of the loaded TRF could be emulsified into crude emulsion. The superiority of Cremophor (R) was attributed to the special arrangement of the surfactant at the oil/water interface, which was confirmed by modelling and docking studies. In the second part of this study, the composition of the secondary ingredients in the TRF-rich SEDDS were optimized by the modified Multisimplex (R) approach. SEDDS were manufactured at pre-defined step-size and tested for their dissolution behavior. Testing was performed sequentially until the optimum composition that can emulsify 50% of the loaded TRF into a stable < 150 nm submicron emulsion was obtained. Optimization end-point was identified when the "membership value" approached 1, which was confirmed by a second Multisimplex (R) run. Overall, this study demonstrated the utility of docking studies and the Multisimplex (R) approach in product development when little is known about the experimental "design space".

• 出版日期2012-4-15