ABSTRACT
Drug development pipelines have changed dramatically over the last 40 years, yielding a number of candidate molecules with challenging properties that limit drugability.1-4 These properties range from physicochemical stability to permeability, with the most signicant limitation for oral molecules being poor aqueous solubility. Driven by the advent of high throughput screening and the need to enhance molecular structure to facilitate target binding efciency, compounds have evolved lower solubility, making many of the lead compounds in modern pipelines more insoluble than marble.5 This has led to the characterization of many modern active pharmaceutical ingredients as “brick dust.” These compounds are often physically delineated by a higher melting temperature and larger melting enthalpy.6 Another dening characteristic of many modern new chemical entities has been a transition in lipophilicity,7 increasing to high log P values thereby reducing the ability to wet and subsequently dissolve. Additionally, the higher degree of molecular complexity challenges the ability to generate a stable crystalline drug substance. Other non-ideal properties such as chemical instability, the need for nontraditional release proles, and/ or alternative delivery routes makes solid dispersion technology an ideal approach for enabling next-generation therapies.
