Design, Translational, and Regulatory Barriers in Advancing Nanocrystal-Based Therapeutics

Barriers to Advancing Nanocrystal-Based Therapeutics

Abstract

Poor aqueous solubility is one of the major critical issues that hinder the clinical integration of nearly 90% of the drug candidates in the discovery pipeline (1, 2). Addressing that biopharmaceutical problem, nanocrystal-based drug formulations have emerged as a promising solution, particularly for BCS Class II and IV drugs, where oral absorption is comprised mainly due to inadequate solubility or permeability (1, 2). Nanocrystals consist of crystalline particles of the pure drug, stabilized by minimal concentration of excipients and do not contain any carrier system (1, 2). By engineering these crystalline active ingredients into the nanometer range, dissolution velocity is significantly increased, resulting in better aqueous solubility, improved bioavailability and potential dose reduction (1-3). However, several translational, design, and regulatory barriers continue to limit the seamless transition of nanocrystal therapeutics into clinical use (1-4).