Novel manufacturing strategies for poorly water-soluble drugs

The presented research focuses on innovative additive manufacturing platforms and pharmaceutical formulations to improve the efficacy of the delivered drug. Drug discovery is a time-consuming and expensive process costing approximately US $1.8 billion and involves two major steps namely target identification and lead optimization. 90% of drugs currently in the pipeline and 36% marketed drugs fall in one of the two biopharmaceutical classes suffering poor aqueous solubility (BCS-II, and IV). The development of supersaturating drug delivery systems such as amorphous solid dispersions and pharmaceutical cocrystals which stabilize the drug in their high-energy or other rapidly dissolving forms while maintaining a sustained level of supersaturation over the luminal surfaces has proven efficient in solving the problem at hand. Further, with the advances in additive manufacturing processes, 3D printing personalized medicine, rapid prototyping of formulations, and added versatility of designing structures to improve the efficacy of the delivered drug have become a possibility. Here we show the utility of hot-melt extrusion and 3D printing individually and synergistically in manufacturing amorphous solid dispersions and cocrystal compositions with improved in vitro performance and stability. The conducted research investigated the influence of different processing parameters and formulation variables involved in fused deposition modeling 3D printing and selective laser sintering processes on the solid-state, stability, and quality of the 3D amorphous solid dispersions and hot-melt extruded pharmaceutical cocrystals for challenging drugs. From the conducted research, results, and observations it can be concluded that fused deposition modeling and selective laser sintering can be used for manufacturing pharmaceutical dosage forms containing amorphous solid dispersions of heat-sensitive, light-sensitive and poor glass forming drugs where the release of the drug from the dosage forms can modulate by controlling formulation and processing variables. Moreover, pharmaceutical cocrystals of heat-sensitive drugs with poor glass-forming ability manufactured using polymer-assisted hot-melt extrusion processing can be engineered to show a pH-dependent targeted release to improve their stability and performance in vitro.