Amorphous Solid Dispersions (ASD) – Considerations in Product Development

• ASD in current market place  
• Challenges and considerations in early and late phase ASD development
• Technologies and Analytical Characterization
• The Future - Novel materials, Data Science and Modelling

Amorphous Solid Dispersions (ASD) are enabling delivery systems that primarily improve the oral bioavailability of poorly soluble, crystalline drugs. The development of ASD is challenging as it involves conversion of drug from a thermodynamically stable crystalline state to a kinetically stabilized amorphous state and retention of the amorphous state from the time of manufacturing to the time of in-vivo drug release upon dosing, a period of several months to years. The formulation composition and technologies used to manufacture, package and characterize ASD in a market product play an important role in the kinetic stabilization process and determination of drug release metrics. Considerations in early phase development include establishing solubility and supersaturation limits, determining drug polymer affinity and enabling a molecular level dispersion with high drug loading with a suitable technology. The challenges in late phase development include conversion of ASD to an acceptable market product governed by physical and mechanical properties, scale-up of technology and commercial registration, ensuring stability of ASD through shelf-life storage and acceptable performance in clinical and relative bioavailability studies. Throughout the development process, analytical characterization of ASD plays a key role in determining its quality attributes. While several ASD products have been successfully developed and marketed, the advent of new stabilizing materials and data science and modelling approaches can further enhance our knowledge of ASD as a delivery system, reduce cycle time of development and provide highly differentiated and value-added medicines to patients.

Raman Iyer, Associate Director, Technical R&D, Novartis Pharmaceuticals Corp.