(585f) The in Situ Analysis and Characterization of the Coprecipitation of a Model Drug and Polymer

Williams, J. V., Food and Drug Administration
Shah, R. B., Food and Drug Administration
Wu, H., FDA

Coprecipitation is a solid dispersion technique whereby a drug substance and polymer simultaneously precipitate out of solution. The technique has been adopted to enhance the bioavailability of poorly water-soluble drugs. While this process helps meet the need for improved drug delivery systems, it has not been well-studied to the point where process variability can be understood and controlled. ?Quality by design? principles provide us the opportunity to understand and control the variability, such as formulation variables and particle growth dynamics, during the coprecipitation process. Thus, we can achieve desirable drug release profiles.

In this work, we designed and characterized a co-precipitation process, using a design of experiment strategy, observing which formulation variables, such as solvent type, anti-solvent addition rate and drug/polymer ratio, have the greatest affect on drug product. We then implemented two in situ technologies, FBRM and PVM to elucidate the effects of crystal nucleation and growth during coprecipitation, on the properties of the drug substance, excipient and drug/excipient complex. The metastable zone width was calculated and interpreted, such that the regions of optimum process conditions were identified.