Over the last few decades, hot melt extrusion (HME) has emerged as a successful technology for a broad spectrum of applications in the pharmaceutical industry. As indicated by multiple publications and patents, HME is mainly used for the enhancement of solubility and bioavailability of poorly soluble drugs. This review is focused on the recent reports on the solubility enhancement via HME and provides an update for the manufacturing/scaling up aspects of melt extrusion. In addition, drug characterization methods and dissolution studies are discussed. The application of process analytical technology (PAT) tools and use of HME as a continuous manufacturing process may shorten the drug development process; as a result, the latter is becoming the most widely utilized technique in the pharmaceutical industry. The advantages, disadvantages, and practical applications of various PAT tools such as near and mid-infrared, ultraviolet/visible, fluorescence, and Raman spectroscopies are summarized, and the characteristics of other techniques are briefly discussed. Overall, this review also provides an outline for the currently marketed products and analyzes the strengths, weaknesses, opportunities and threats of HME application in the pharmaceutical industry.

The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus® were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses. This work reports the successful fabrication of solid-dispersion filaments with an API dispersed in HPMC based matrix via HME technology, and the production of zero order controlled release tablets with different 3D structures (tablets #3, 5, 6, and 9) using a 3D printer.

Floating dosage forms are an important formulation strategy for drugs with a narrow absorption window and low intestinal solubility, and for localized gastric treatment. Novel floating pellets were prepared using the hot-melt extrusion (HME) technology. Uniformly foamed strands were created by liquid injection pumping and screw configuration modification. The ammonio methacrylate copolymer (Eudragit® RSPO) foaming structure was formed by a liquid-vapor phase transition inside the strand upon die exiting resulting from the sudden decrease in external pressure, vaporizing the liquid ethanol and vacating the extruded material. This generated uniform vacuous regions in the extrudate. The pellets’ internal structure was investigated using scanning electron microscopy (SEM). The formulation constituents’ and processing parameters’ effects on the drug release profiles, floating force, and the pellets’ micromeritic properties were evaluated by design of experiments: all formulations showed zero lag time and excellent floating strength, indicating immediate-floating pellet formation. The pellets’ drug release profiles were controlled by multiple independent variables at different time points (≤24 h). Drug loading significantly affected drug release within the first hour; the hydroxypropyl methylcellulose (HPMC) content thereafter. Understanding the variables’ effects on the formulations allows for the tailoring of this delivery system to obtain various drug release profiles.

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The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6–11 s) and more than 95% dissolution in 5 min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.