Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

Abstract

Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in particular, it offers the possibility of improving drug bioavailability. HME involves the mixing of a drug with one or more excipients, in general polymers and even plasticizers, which can melt, often forming a solid dispersion of the drug in the polymer. The molten mass is extruded and cooled, giving rise to a solid material with designed properties. This process, which can be realized using different kinds of special equipment, may involve modifications in the drug physicochemical properties, such as chemical, thermal and mechanical characteristics thus affecting the drug physicochemical stability and bioavailability. During process optimization, the evaluation of the drug solid state and stability is thus of paramount importance to guarantee stable drug properties for the duration of the drug product shelf life. This manuscript reviews the most important physicochemical factors that should be investigated while designing and optimizing a hot melt extrusion process, and by extension, during the different pre-formulation, formulation and process, and post-formulation phases. It offers a comprehensive evaluation of the chemical and thermal stability of extrudates, the solid physical state of extrudates, possible drug-polymer interactions, the miscibility/solubility of the drug-polymer system, the rheological properties of extrudates, the physicomechanical properties of films produced by hot melt extrusion, and drug particle dissolution from extrudates. It draws upon the last ten years of research, extending inquiry as broadly as possible.

An Undergraduate Study for the Comparison of Dissolution Profiles using 3D Printed PVA and Commercial Paracetamol Tablets

“…This was lower than the theoretical value as a result of adhesion of the fine API powder to the walls of the barrel of the HME during the extrusion process. [15] The tablets showed similar values to the filament indicating that no degradation took place during the printing process. Tablets also showed high uniformity in size and weight (mean dimensions: 12.93 mm diameter x 4.08 mm height, mean weight: 1.2459 g) which rendered a concise method of manufacture.…”

Bio- Fortification of Angelica gigas Nakai Nano-Powder Using Bio-Polymer by Hot Melt Extrusion to Enhance the Bioaccessibility and Functionality of Nutraceutical Compounds

“…Thermal analysis shows the behavior of the solid extrudate materials as a function of temperature and time. It provides information about particle morphology and crystallization, as well as solid transformations during heating [14]. The glass transition temperature (Tg) is an important property of an amorphous material.…”

“…Twin screw extrusion generates high shear stress with a higher degree of mixing capacity than the single screw extruder. Hot melt extrusion (HME) equipped with twin screw is widely used in the pharmaceutical and food industries, to develop solid composites with a nanosized particle of the active compounds [14] ( Figure 2). The HME extrusion process is generally carried out above the gelling temperature of the polymer components, to achieve the optimal miscibility of the active compounds and polymer [15].…”

“…Hydrophilic plasticizers have a significantly positive effect on the increase in dissolution rate. During the HME process, biopolymers are depolymerized, and polymer chains break down due to thermal and high shear stress [14]. During the HME process, the active compounds are supposed to be dispersed into a polymeric matrix where active compounds are present as dissolved particles or as a solid solution [19].…”

Drug Incorporation into Polymer Filament Using Simple Soaking Method for Tablet Preparation Using Fused Deposition Modeling

“…HME has been used to mask drug bitterness, improve drug dissolution, and enable sustained drug release. 15) As HME is applicable for the preparation of polymer filaments for FDM printing, the preparation of polymer filaments for 3D printing has been reported. 16) Drug-loaded polymer filaments for FDM printing can also be prepared by simply soaking the polymer filament in a drug solution.…”