Applications of hot-melt extrusion in drug solubility enhancement: recent innovations and future directions.

Objective: Hot-melt extrusion (HME) has emerged as a solvent-free, scalable, efficient, and continuous process to overcome the challenges of poor solubility in new drug entities. Using HME technique, crystalline drugs are converted to amorphous solid dispersions (ASDs), which significantly enhances their dissolution rates and oral bioavailability. This review is aimed to provide a comprehensive review of HME as a transformative strategy in pharmaceutical manufacturing.

Significance of review: This review critically analyzes the mechanistic insights of solubility enhancement using HME, its advantages over traditional methods, key formulation components, and the influence of processing parameters on drug stability and performance. Moreover, translational case studies emphasizing the applications of HME in solubility enhancement, and the growing role of artificial intelligence (AI) and molecular modeling are discussed in detail. It also covers the patent landscape relevant to HME and compares HME with other methods of ASD preparation.

Key findings: The literature indicated that recent technological advancements in HME including nanocrystal generation, co-crystallization, hybrid methods, and three-dimensional printing integration garners its immense potential and highlighting its wide scope of applications. Recent integration of AI and machine learning (ML) with HME has emerged as a forward-looking strategy that can be employed successfully in the optimization of formulation design and manufacturing.

Conclusions: The continuous processing capabilities, adaptability to various dosage forms, and compatibility with modern drug development strategies have highlighted the importance and versatile applications of HME. Moreover, growing regulatory acceptance and continuous innovations have placed HME at the forefront of pharmaceutical development for poorly soluble compounds.