"Vitamin E" fortified parenteral lipid emulsions: Plackett-Burman screening of primary process and composition parameters.

The objective of this study was to screen the effect of eight formulations and process parameters on the physical attributes and stability of "Vitamin E"-rich parenteral lipid emulsions. Screening was performed using a 12-run, 8-factor, 2-level Plackett-Burman design. This design was employed to construct polynomial equations that identified the magnitude and direction of the linear effect of homogenization pressure, number of homogenization cycles, primary and secondary emulsifiers, pre-homogenization temperature, oil loading, and ratio of vitamin E to medium-chain triglycerides (MCT) in the oil phase on particle size, polydispersity index, short-term stability, and outlet temperature of manufactured emulsions. The viscosity of vitamin E was reduced from 3700 (100%) to 64 mPa.s (30%) by MCT addition. As viscosity is critical for efficient emulsification, vitamin/MCT ratio was the most significant contributor for the stability of emulsions. Particle size increased from 236 to 388 nm, and percentage vitamin remaining emulsified after 48 h dropped from 100 to 73% with increase in vitamin/MCT ratio from 30/70 to 70/30. Significant decrease in particle size and PI, and an increase in outlet temperature were also observed with increase in homogenization pressure and number of homogenization cycles. Emulsifiers and oil loading, however, had insignificant effect on the responses. Overall, stable submicron emulsions at vitamin/MCT ratio of 30/70 could be prepared at 25,000 psi and 25 cycles in ambient conditions. The identification of these parameters by a well-constructed design demonstrated the utility of screening studies in the "Quality by Design" approach to pharmaceutical product development.