Improving Amorphous Solid Dispersions

26. January 2018

Abstract

The understanding of amorphous solid dispersions has grown significantly in the past decade. This is evident from the number of approved commercial amorphous solid dispersion products. While amorphous formulation is considered an enabling technology, it has become the norm for formulating poorly soluble compounds. Despite this success, improvements can still be made that enable early development formulation decisions, to develop a rationale for selecting a manufacturing process, to overcome degradation and phase separation during processing, to help achieve physical stability during storage, and to optimize dissolution behavior. The purpose of this literature review is to present recently reported strategies for improving the development and performance of ASDs. The benefits and limitations of each strategy as well as recent relevant case studies will be presented in this review. The strategies are presented from three different aspects: (a) prediction techniques that enable formulation decisions, (b) manufacturing considerations that help produce physically and chemically stable ASDs, and (c) formulation strategies that enhance dissolution behavior.

Conclusion

Great strides have been made in the formulation and process design of amorphous solid dispersions. However, despite commercial success and a wealth of information, improvements could still be made to enhance the development and performance of ASDs. The application of predictive tools will enable a much more efficient early development process, eliminating the need for long-term stability screening studies and enabling informed formulation decisions. After early development, a rationale for choosing a manufacturing technique should also be employed to ensure a high-quality ASD.

The processing of high melting point compounds with poor organic solvent solubility remains another burden for the development of ASDs. Drug degradation is a signif- icant drawback of extrusion, but the current work in this area bridges process understanding with molecular level understanding to significantly reduce degradation during extrusion.

Finally, the explosion of interest in the dissolution behavior of ASDs has brought a new level of understanding in just the past few years. As we develop an understanding of ASDs during dissolution, improvements in ASD formulation can be adopted to enable better development decisions and excellent bioavailability enhancement.