Use of in situ Raman, FBRM, and ATR-FTIR probes for the understanding of the solvent-mediated polymorphic transformation of II-I etiracetam in methanol

The objective of the present paper is to show the utility of combining distinct online and in situ probes, tracking both the solid and the liquid phases, to come to a full understanding of the mechanism underlying polymorphic transformations. The study focuses on the batch crystallization process of etiracetam (racemic intermediate to the synthesis of levetiracetam [Keppra, UCB Pharma], presenting two enantiotropically related crystallographic forms) in methanol, as this process relies on a polymorphic transformation in solution prior to the isolation of the final compound. The polymorphic transformation is shown to follow a solvent-mediated polymorphic transformation mechanism, which is characterized by three successive phases. Identification and understanding of each of these phases requires the knowledge on the nature of the crystallographic form (Raman probe), the variations in particle size distributions (FBRM probe) as well as the solute concentration in solution (ATR-FTIR probe), showing the necessity of combining these different online analyzers. © 2011 American Chemical Society

Development and field application of a new combined vaccine against Peste des Petits Ruminants and Sheep Pox

A combined vaccine against Peste des Petits Ruminants (PPR) and Sheep/Goat Pox (SGP) was developed and applied in the field, using a new association of vaccine strains: PPR Nigeria 75 strain with a titre of 104.1 TCID50 and Sheep Pox Romania strain with a titre of 104.0 TCID50. Safety and efficacy were evaluated on goats and sheep in comparison with monovalent PPR and SGP vaccines. Goats were challenged by PPR virulent strain and sheep by SP virulent strain. The result shows that the combined PPR/SGP vaccine confers a good protection against both PPR and SGP infection with no significant difference with monovalent vaccines. The combined vaccine was used in the field on sheep flocks and good sero-conversion was detected for both diseases as soon as 14 days post vaccination

A crystallisation development workflow for the manufacturability improvement of active pharmaceutical ingredients

More than 70% active pharmaceutical ingredients (APIs), in the development pipeline, exhibit poor manufacturability (e.g., Isolation, flowability, tabletability) posing major challenges in the production of consistent product with desired performance1. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated as a critical process to improve manufacturability of the drug