Anti-inflammatory drug nanocrystals: state of art and regulatory perspective

Anti-inflammatory drugs have been prescribed extensively for a wide range of diseases. Combined with over-the-counter use, approximately 30 billion doses of non-steroidal inflammatory drugs (NSAIDs) are consumed annually in the USA. The global market of glucocorticoids (GCs) is forecast to reach US$ 8.6 billion by 2025. Severe adverse effects have been reported for NSAIDs, GCs, and COX-2 selective NSAIDs (COXIBs). Furthermore, the overwhelming majority of these drug substances are BCS class II, which limits their bioavailability due to poor water solubility. Drug nanocrystals, a carrier-free nanosystem, can increase saturation solubility, dissolution rate, and the mucoadhesiveness of these drugs. The enhancement of these properties was highlighted in our findings. These features improve the efficacy and safety of anti-inflammatory drugs. In this review, we show that drug nanocrystals are an attractive strategy that contributes to an important shift in the development of innovative products for different routes of administration. The possibility of targeting can minimize the adverse effects and improve the efficacy in the management of inflammatory conditions. We comprehensively review the critical quality attributes (CQAs) in the anti-inflammatory drug nanocrystals preparation, which are fundamental to developing a successful marketable product. Despite the advantages, maintaining properties such as average particle size, surface properties, and physicochemical stability of these preparations during shelf life poses challenges to be overcome.