(106d) Production of Pharmaceutical Nanoparticles Using An Environmentally-Safe Emulsion Template
- Conference: AIChE Annual Meeting
- Year: 2009
- Proceeding: 2009 Annual Meeting
- Group: Food, Pharmaceutical & Bioengineering Division
- Time: Monday, November 9, 2009 - 1:10pm-1:30pm
Recently, the poor water-solubility of many drugs has become a focal point of the pharmaceutical industry. Pharmaceutical nanoparticles have been proven to aid this problem by achieving a faster solubility rate and an increased bioavailability. Nanoparticles have driven the innovation of several novel techniques to administer safe and effective drug levels. Furthermore, nanoparticles exhibit many other unique advantages for drug delivery including: targeting, variable optical properties, and the ability to be functionalized. Traditional nanoparticle synthesis techniques work by breaking particles down mechanically, by building them using highly-mixed crystallizations, or by the solidification of hot lipid emulsions. However, a newer technique has been developed called the emulsion-diffusion process. In this process, emulsion droplets act as the site for the nucleation and subsequent growth of pharmaceutical nanocrystals. Specifically, the active drug is dissolved in the dispersed oil phase of an emulsion that is partially miscible with the continuous water phase. High pressure homogenization breaks droplets down to the nano-scale which are introduced into a well mixed system of additional anti-solvent; this quickly extracts the partially miscible oil phase resulting in a controlled, surfactant-stabilized crystallization inside the shrinking droplet. The product of this process is a monodisperse suspension of 100nm diameter nanoparticles that remain stable for several days, a significant improvement over existing techniques. A model has been derived for the behavior of the emulsion droplets in presence of excess aqueous phase based on the diffusion of the different phases. A focal point of this technique is the entire process can be conducted using only FDA recognized safe ingredients. Two different environmentally-safe dispersed phases have been explored: Triacetin and n-Butyl Lactate, as well as, two different drugs: Griseofuvlin and Ascorbyl Palmitate. Triacetin-based suspensions have created relatively dilute solutions containing a monodisperse suspension of nanoparticles as small as 86 nm in diameter, while n-Butyl Lactate-based emulsions produced a significantly more concentrated suspension with a consequential larger particle size of 200-300 nm in diameter. Both drugs exhibited similar behavior and had little effect on final particle size. This process is a scalable, two-step operation with the ability to create large volumes of concentrated nanosuspensions for use in drug delivery without the use of harmful solvents.