Dr. Christian Lübbert, amofor GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany

An amorphous solid dispersion (ASD) is a state-of-the art formulation technique to enable sufficient bioavailability of poorly-water-soluble active pharmaceutical ingredients (APIs). In an ASD, the API is dissolved in a polymer to prevent recrystallization during shelf life.

Intermolecular interactions between API and polymer must be understood to predict the optimal API load in an ASD, the ASD shelf life or ASD processing parameters for manufacturing processes (e.g. spray drying). This webinar will elucidate the strong potential of combining dynamic vapor sorption (DVS) measurements with thermodynamic modeling as universal tool for formulation development far beyond regular water sorption determinations.

Based on sorption measurements in an ASD and thermodynamic modeling, the crystalline solubility of an API in a polymer is predictable quickly requiring minimal sample amount (<2mg API per API/polymer combination). This method is beneficial compared to techniques like the melting point depression method via differential scanning calorimetry, as the sorption data is acquired at storage test relevant temperatures and not diffusion velocity limited. Additionally, a method to predict the ASD shelf life only based on DVS and modeling is presented. One DVS measurement characterizing the crystallization velocity of the API at harsh conditions (to obtain the glass stability of the pure API) and one ASD diffusion measurement (to obtain the viscosity of the ASD as function of relative humidity). With this minimal data set, the shelf life of an ASD at different storage and humidity conditions (months to years) can be predicted in advance by the measurements (few days) and the modeling only.

During spray drying process development, the optimal solvent or solvent mixture must be identified dissolving polymer and API sufficiently. This is again possible with DVS only, as sorption measurements combined with thermodynamic modeling allow via extrapolations even reliable miscibility and solubility predictions.

The entire ASD formulation development is enhanced by DVS measurements combined with thermodynamic modeling. Scientists have a powerful combined tool at hand, as experiments require minimal sample amount and results from calculations are obtained within minimal time.