Use of Lecithin As an Antistatic Agent in Nonconductive Crystallization Slurries for Isolating Pure Active Pharmaceutical Ingredients

Static buildup in glass-lined processing train during pure API crystallizations in organic solvents can result in costly glass damage to the vessel internals, and presents a potential safety risk of fire or explosion. The propensity for static buildup is directly related to the conductivity of the solvent system and is especially high for nonpolar organic solvents such as toluene and heptane. Lecithin is a zwitterionic organic surfactant commonly used in the food and pharmaceutical industry. Lecithin has been proposed as an antistatic agent due to its relatively high solubility in nonpolar organic solvents, as well as its charge carrying capabilities when dissolved. Because lecithin is routinely used in the pharmaceutical industry including in final drug product formulations, it has the advantage of having a reduced regulatory hurdle for implementation during API processing relative to other commercial antistatic agents that do not have precedence for pharmaceutical applications. Experimental results show that addition of lecithin at ppm levels is sufficient to increase solution and pure API slurry conductivity to above an acceptable threshold that reduces the risk of static charge buildup with a linear relationship between conductivity and lecithin concentration demonstrated. Noteworthy is the observation that the amount of lecithin required is related to the surface area of the API solids, as sufficient lecithin must be added to coat the solid surface with approximately monolayer coverage before the excess lecithin is solvated and electrically active in solution. Finally, head-to-head comparison studies with and without lecithin for three API compounds have shown that lecithin does not significantly impact the crystallization process or the physical properties of the API generated.