Liquid-Liquid Phase Separation and Crystallization

On Demand Webinar

Liquid-Liquid Phase Separation and Crystallization

Development and Monitoring of Crystallization Process Exhibiting Liquid-Liquid Phase Separation

Liquid-Liquid Phase Separation and Crystallization
Liquid-Liquid Phase Separation and Crystallization

Liquid-Liquid Phase Separation (LLPS), also known as oiling out or phase demixing, is often encountered during the development of an Active Pharmaceutical Ingredient (API). This phenomenon is characterized by the formation of a dispersed phase (solute rich droplets) and a continuous phase (solute lean) from an initial single liquid phase.  Liquid-Liquid Phase Separation (LLPS) can have signficant effects on crystal purity and scale-up.

This presentation describes a strategy employed to design and develop robust, scalable crystallization processes that avoids Liquid-Liquid Phase Separation (LLPS) or oiling out. 

Moussa Boukerche - Eli Lilly
40 Minutes

Experimental and modeling approaches are presented for an intermediate and a final Active Pharmaceutical Ingredient (API) exhibiting Liquid-Liquid Phase Separation (LLPS). This webinar focuses specifically on examples where Liquid-Liquid Phase Separation (LLPS) occurs in a ternary system (solute/solvent/anti-solvent). The solvent and anti-solvent are fully miscible in the P,T phase diagram but the presence of the solute forces a spinodal decomposition that inhibits/delays the formation of crystals.  A thermodynamic and kinetic development is proposed to explain why:

  1. The rich and lean phases have the same supersaturation (i.e. same chemical potential/Gibbs free energy) once Liquid-Liquid Phase Separation (LLPS) occurs
  2. The supersaturation level in each individual phase should be in theory similar (or lower) to the supersaturation of the original single phase (i.e. before the demixing)
  3. The oil droplets should crystallize preferentially
Liquid-Liquid Phase Separation and Crystallization
Dr. Moussa Boukerche

Guest Presenter

As a Senior Consultant Engineer at Eli Lilly, Moussa Boukerche is currently responsible for the design and development of crystallization processes in API manufacturing.  Prior to Eli Lilly, Moussa worked in the field of industrial crystallization for several companies, including SANOFI (France), Pfizer (UK), and Aughinish Alumina (Ireland).

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