(34g) Mechanistic Insights into a Process Intensification Strategy in Pharmaceutical Manufacturing
- Conference: AIChE Annual Meeting
- Year: 2018
- Proceeding: 2018 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Sunday, October 28, 2018 - 5:36pm-5:57pm
Co-agglomeration of APIs and excipients has been achieved using Emulsion Solvent Diffusion(ESD). Despite its initial success, developing a robust ESD process still remains a challenging task. The success of ESD hinges on selecting the right combinations of solvents, antisolvents, API concentration and emulsifier concentration. This is further compounded by the fact that in ESD, the Primary Particle Size Distribution(PSD) and the Agglomerate Size Distribution(ASD) need to be controlled simultaneously during the diffusion process which gives less number of degrees of freedom from a process control standpoint.
Although much work has been done on finding the effect of process conditions(flow rate, concentration of API) on the ASD, there is still a huge knowledge gap in literature regarding the mechanisms of the fundamental rate processes behind ESD. This work delves into gaining a mechanistic understanding of the ESD by giving systemic perturbations to the process and studying the system response characteristics. Process Analytical Technologies(PAT) tools viz. FBRM have also been used in the process to monitor the evolution of the Chord Length Distribution. It has been shown that use of in-situ PAT tools gives novel insights into the mechanisms of ESD process that would have been otherwise unattainable by just studying the end of batch response characteristics to systemic perturbations.