(730a) Emulsifier Studies and Stability Optimization of the Production of Pharmaceutical Nanosuspensions Using Emulsion Precipitation | AIChE

(730a) Emulsifier Studies and Stability Optimization of the Production of Pharmaceutical Nanosuspensions Using Emulsion Precipitation


Romanski, F. - Presenter, Rutgers University
Jayjock, E. - Presenter, Rutgers University
Tomassone, M. S. - Presenter, Rutgers University

In this work, we study the effect of a wide range of emulsifiers on the production of poorly water soluble drug nanosuspensions using an emulsion precipitation technique. The synthesis methodology utilizes a scalable three-stage operation where a partially water-miscible emulsion is formed and subsequently precipitated to form the nanosuspension. The entire process was conducted using only generally regarded as safe (GRAS) components, making the process highly desirable for food and pharmaceutical applications. Specifically, three different classes of emulsifier were tested for effectiveness for both formation of a stable emulsion, and formation of stable nanoparticles. The three classes of emulsifier (sorbitan esters, sucrose esters, and propylene glycol esters) were compared with a lecithin emulsifier, which was commonly used for this process. Ibuprofen, a model poorly water soluble drug was used as a model drug and was processed using an oil-water emulsion consisting of either n-butyl lactate or ethyl acetate as the oil phase. A wide range of Hydrophilic-Lipophilic Balance (HLB) index surfactants were tested by the mixing of two similar structured surfactants of contrasting HLB-value at precise concentrations. It was found, counter-intuitively, that despite the fact that certain values of HLB consistently produced the best emulsion, in terms of smallest droplet size and longest stability, this did not correlate with the subsequent production of particles from the emulsions. In fact, it was found that although sorbitan esters, sucrose esters, and propylene glycol esters all produced stable emulsions in the HLB range of 10-12, only the sorbitan esters and propylene glycol esters successfully produced nanosuspensions from the emulsions. It was found that sorbitan esters were able to produce the smallest particle size nanosuspension with a mean particle diameter of 110 nm. It was subsequently determined that the effect of the surfactant molecular weight, morphology and interactions can negatively impact the dissolution of the droplets required to produce a nanosuspension. Finally, suspensions were evaluated for long term stability by monitoring the size over time and the zeta potential of the suspensions. This work has revealed that while the HLB index can consistently predict emulsions stability, this does not translate into a successful production of nanosuspensions as previously thought. Additionally, it has been found that several classes and mixtures of non-ionic surfactants can be used to create GRAS emulsion-precipitated nanosuspensions, further adding to the robust nature of the methodology.