Impact of downstream processing on crystal quality during the precipitation of a pharmaceutical product

In pharmaceutical industries, active pharmaceutical ingredients (API) are made of crystals whose properties must be controlled because they influence the end-use properties of the drug. Even if crystal quality is mainly determined during the precipitation step, downstream processing also has an influence. In this study, the influence of washing on the crystal size and shape was analyzed. For the API being considered, different impurities have to be removed from the final suspension by filter cake washing. The efficiency of the washing steps was measured by different types of characterization on the solid phase (differential scanning calorimetry, scanning electron microscopy, and size distribution) and on the remaining filtrate (concentration of impurities). A second component also coprecipitates with the API. A specific study has been carried out on the withdrawal of this by-product and on its impact on the evolution of the crystalline form during washing steps. It was found that three filter cake washings allow us to remove all the impurities and to obtain a pure crystalline form.

Graphical AbstractThe efficiency of the washing steps of API crystals was measured by different types of characterization on the solid phase (differential scanning calorimetry, scanning electron microscopy, and size distribution) and on the remaining filtrate (concentration of impurities by ICP). These methods permitted also to determine the mechanisms of washing and to put into light the coprecipitation of API with a by-product.Figure optionsDownload as PowerPoint slide