Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Abstract

Abstract. Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

3D Printing Factors Important for the Fabrication of Polyvinylalcohol Filament-Based Tablets

“…15,17) Hot-melt extrusion is an established method that uses an extruder. 23,24) In contrast, the soaking method involves the simple soaking of a polymer filament in organic solvent saturated with the drug (in this case, a drug ethanoic solution) and the drug diffuses into the polymer filament. The soaking method is limited to drugs soluble in organic solvent, and the resulting loaded amount of drug is lower than obtained using the hot-melt extrusion method.…”

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

“…A twin screw extruder, compared to single screw extruder, provides the following advantages: a higher dispersibility, easier feeding, a lower risk of overheating, higher process productivity, and a better modulation of process parameters [9,19,20].…”

“…Materials can be thrown into the extruder, moved towards the die and homogeneously blended by rotating screws, and extruded from the die (or an orifice) [8][9][10][11]. During the HME process, the temperature of barrels is designed above the glass transition temperature (T g ) and sometimes over the melting temperature (T m ) of polymeric substances, and the drug can be molecularly dispersed in the polymer matrix [9,12,13].…”

“…Conclusively, the use of SP in HME processing can improve solubility and the bioavailability of poorly water-soluble drugs [9,14,16,17]. So far, the HME technique has been used principally to make solid dispersions of organic molecules, which have low molecular weight and poor water solubility, with appropriate polymers (i.e., cellulose derivatives, poly (ethylene-co-vinyl acetate), polyethylene glycol, polyvinylpyrrolidone, and SP) [9,14,16,18]. Herein, ZnSO 4 /SP nanocomposites (NCs) were fabricated by HME processing, and their physicochemical and biosafe properties were investigated.…”

Development of an Ointment Formulation Using Hot-Melt Extrusion Technology

“…In HME process, rotating screws drive the physical mixture (drug+inactive excipients) above the glass transition temperature (Tg) and/or above the melting temperature (Tm) based on the type of material used in the formulation. Thus, uniform mixing of active pharmaceutical ingredient and thermoplastic binders, polymers, or both is achieved (3). Thus, HME technology is used to formulate granules, pellets, immediate and controlled release tablets, and transdermal and transmucosal drug delivery systems (4)(5)(6).…”