In recent years, the demand for developing patient-centric dosage forms is increasing enormously with the increasing patient population. Much research is ongoing exploring various additive manufacturing techniques for developing pharmaceutical medications. Poor solubility of drug substances and underdeveloped manufacturing strategies are majorly affecting the pharmaceutical industry's revenue. Developing intravenous dosage forms for drug substances with poor solubility will affect the revenue of the pharmaceutical industries. Thus, improving solubility remains to be the major prerequisite for the developmental scientist. In addition to improving solubility, establishing a robust manufacturing process with commercial viability is also essential. In recent years hot melt extrusion (HME) has been most widely investigated for developing amorphous solid dispersions (ASDs) over other techniques such as spray drying and KinetisolÒ. The process of HME can be coupled with the fused deposition modeling (FDM) three-dimensional (3D) printing technique which is capable of fabricating on-demand patient-centric dosage forms. A continuous manufacturing line can be established by painting HME and FDM 3D printing processes. The quality of the product can be controlled and monitored by employing suitable process analytical technology (PAT) tools. Though the process of the HME-paired FDM 3D printing process has resulted in various advantages compared to the conventional manufacturing process, still many limitations, such as the limited number of polymers, reproducibility, and stability, need to be addressed.

In recent years amorphous solid dispersions (ASD) has gained a tremendous response for improving the solubility of poorly water-soluble drug substances. Despite the stability challenges, various ASD commercial products have been successfully launched into the market over the last two decades. Among various manufacturing approaches, hot melt extrusion (HME) and spray drying techniques have attracted industries attributing to their simple manufacturing processes. In addition, KinetisolÒ, a solvent-free approach, is also being most widely investigated for developing ASDs since the thermal exposure time of the formulations is significantly less compared with the hot melt extrusion process. KinetisolÒ can be employed for developing ASDs of thermolabile drug substances. Another solvent-based technique, electrospinning, is also employed for developing nanofibers-based ASD. However, much research is warranted for the electrospinning process before implementing it in commercial manufacturing. Various critical factors such as drug-polymer solubility, the solubility of the drug in the polymer, drug-polymer interactions, type of manufacturing process, and storage conditions need to be considered for developing a stable and robust ASD formulation. This review mainly focuses on the most advanced manufacturing technologies of ASDs, namely HME, spray drying, KinetisolÒ, and electrospinning, along with a note on the various critical factors that affect the stability of ASD formulations. Keywords: amorphous solid dispersions; hot melt extrusion; spray drying; KinetisolÒ; electrospinning

In today’s world with increasing patient population, the demand for pharmaceutical medications is increasing enormously. However, poor solubility of drug substances and underdeveloped manufacturing process are affecting the revenue of the pharmaceutical industries. Improving the solubility and establishing a robust manufacturing process is the primary prerequisite of the developmental scientists. Among various approaches amorphous solid dispersion has gained a tremendous response for improving the solubility of the drug substances. In addition, the process of hot melt extrusion has attracted the investigators from regulatory agencies and industries. The process of hot melt extrusion involves application of thermal and mechanical energy on to the processing material. The process requires no solvent and is referred as “green technique.” Various factors need to be taken into consideration for developing amorph amorphous solid dispersions. The miscibility of drug and polymer, solubility of drug in polymer, drug-polymer interactions, glass transition temperature, storage conditions majorly influence the stability of the amorphous solid dispersions systems. Though hot melt extrusion is most widely employed for developing amorphous solid dispersions still a lot of research is warranted for developing strategies to formulate high drug loading medications with improved stability. This review article mainly focuses on the instrumentation, and process for developing amorphous solid dispersions by hot melt extrusion with a small note on the various advantages and limitations.

Hot melt extrusion is one of the most popular techniques for the manufacturing of amorphous solid dispersions (ASDs). Over few decades, it has transitioned from lab scale to commercial scale with various products in the market. The current review aims at summarizing various considerations in the formulation development of ASDs using HME. Various types of ASDs from Type I to Type IV are discussed along with the solid state of drug and polymeric carrier in each type. Also, various polymeric carriers used in ASDs are outlined along with information about their glass transition temperature, melting point, hygroscopicity and regulatory status. There are various mechanisms by which the polymeric carriers stabilize the amorphous form of drug in ASDs. These mechanisms are classified as crystallization inhibition, anti-plasticization, intermolecular interactions, and reduction of molecular mobility. These four mechanisms are discussed along with case studies. Finally, various considerations in the formulation of ASDs like, rationale selection of polymers, process design and optimization and stability testing with respect to formulation of ASDs using hot melt extrusion are discussed. In conclusion, the current state of formulating ASDs using HME are discussed and the need for restructuring the formulation approach is mentioned.