Amorphous Formulations For Insoluble Drugs: Rational Design & Practical Approaches On Formulation Screening & Development

By Jim Huang, PhD, Founder & CEO, Ascendia Pharmaceuticals

For poorly water-soluble “brick dust compounds” (Classes II and IV) characterized as high molecular weights, large log P values, and poor water solubilities, the drug absorptions process is often limited by the drug solubility or dissolution rate from the dosage forms. The bioavailability and absorption rate of those compounds into human body can be significantly improved by: 1) an increase in effective dissolution surface area by particle size reduction to the micron or the nanometer size range or by increasing wettability of the hydrophobic drugs, and 2) improvement in the solubility by formation of amorphous nanoparticles or amorphous solid dispersions that form nanoparticles in situ in the GI fluids. However, a comprehensive understanding of amorphous properties and their relationship with in vivo performance are still lagging. Development of characterization techniques to elucidate the structure of amorphous materials, prediction of in vitro and in vivo performance, and custom design of amorphous formulations has remained as the three major needs for the development of an amorphous drug delivery system. The issues associated with amorphous formulations include solid state stability, chemical stability, reproducibility of API manufacturing, impurity of API, stability in aqueous solution, in vitro in vivo performance, process and scale-up, etc.