Molecular modelling and multisimplex optimization of tocotrienol-rich self emulsified drug delivery systems.
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 80 with Cremophor EL in the SEDDS it was possible to emulsify>55% TRF (by weight of the formulation) into submicron (<200 nm) emulsion. With Tween, only 17.5% of the loaded TRF could be emulsified into crude emulsion. The superiority of Cremophor 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 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 run. Overall, this study demonstrated the utility of docking studies and the Multisimplex approach in product development when little is known about the experimental "design space".
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States.
Alaadin
A
Alayoubi
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States.
Seetharama D
SD
Satyanarayanajois
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States.
Paul W
PW
Sylvester
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: nazzal@ulm.edu.
Sami
S
Nazzal
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D000073878:Palm Oil; D010316:Particle Size; D010938:Plant Oils / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D024508:Tocotrienols / Q000737:chemistry*; D014815:Vitamins / Q000737:chemistry*
D004337:Drug Carriers; D004655:Emulsions; D010938:Plant Oils; D011136:Polysorbates; D013501:Surface-Active Agents; D024508:Tocotrienols; D014815:Vitamins; D000073878:Palm Oil; C000515:cremophor EL; D005990:Glycerol