Evaluation of Hot-Melt Extrusion and Injection Molding for Continuous Manufacturing of Immediate-Release Tablets

Abstract

The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its possible advantages in terms of improved sustainability. Tablet-forming agents were initially screened based on processability by single-screw extruder and micromolding machine as well as disintegration/dissolution behavior of extruded/molded prototypes. Various polymers, such as low-viscosity hydroxypropylcellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, various sodium starch glycolate grades (e.g., Explotab(®) CLV) that could be processed with no need for technological aids, except for a plasticizer, were identified. Furthermore, the feasibility of both extruded and molded IR tablets from low-viscosity hydroxypropylcellulose or Explotab(®) CLV was assessed. Explotab(®) CLV, in particular, showed thermoplastic properties and a very good aptitude as a tablet-forming agent, starting from which disintegrating tablets were successfully obtained by either techniques. Prototypes containing a poorly soluble model drug (furosemide), based on both a simple formulation (Explotab(®) CLV and water/glycerol as plasticizers) and formulations including dissolution/disintegration adjuvants (soluble and effervescent excipients) were shown to fulfill the USP 37 dissolution requirements for furosemide tablets.

3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs

“…no need for solvents, scalability, possibility of continuous manufacturing and patentability) and improvement of product characteristics (e.g. versatility, possibility of obtaining solid dispersions/solutions of the active ingredient) [10]. Molded functional containers do represent a step forward in drug delivery as they would enable an independent development of the contents and the shell, thereby offering important benefits from both the regulatory and technical point of view, e.g.…”

Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers

“…In addition to the narrow absorption window and the intestinal efflux proteins further decrease its bioavailability [2]. Khandavilli et al prepared high-solubility crystalline hydrates of Na and K furosemide salts to improve the poor solubility behavior [3], while other researchers have created several alternative drug carriers, like supramolecular complexes [4,5], hot-melt extrusion products [6], nanocapsules [7], microspheres [8] and halloysites [9] to overcome the unfavorable drug features. Drug-loaded nanofibrous delivery systems could be a promising alternative in case of furosemide, offering unique properties which contribute to the increase of bioavailability with a highly porous structure and a high surface-area-to-volume ratio, and enabling the preservation of the initially crystalline drug in amorphous form in the fibers, either in solid dispersion or in solid solution [10][11][12].…”

Comparison of fused-filament fabrication to direct compression and injection molding in the manufacture of oral tablets

“…However, it is not a requisite to melt process formulations for injection moulding applications. The literature offers examples of direct feeding of powder blends for the manufacture of drug dosage forms via injection moulding (Cuff and Raouf, 1999;Eggenreich et al, 2016), including continuous manufacturing processes (Mascia et al, 2013;Melocchi et al, 2015). The technology is also being investigated for tablet coating applications (Desai et al, 2018a(Desai et al, , 2018bPuri et al, 2018).…”

“…Despite the technical hurdles, there is a growing interest in the utilization of the technology for pharmaceutical applications (Jamróz et al, 2017;Norman et al, 2017;Prasad and Smyth, 2016). Researchers have investigated the use of the process to make oral dosage forms such as tablets (Beck et al, 2017;Chai et al, 2017;Goyanes et al, 2015bGoyanes et al, , 2015cGoyanes et al, , 2014Long et al, 2017;Okwuosa et al, 2016;Solanki et al, 2018;Verstraete et al, 2018),caplets (Goyanes et al, 2016b(Goyanes et al, , 2015d, among other more intricate geometries, compositions and functions (Genina et al, 2017;Maroni et al, 2017;Melocchi et al, 2015;Sadia et al, 2018). Other than the ready production of tablets with complex shapes, a primary driver for the technology is the possibility of the tailored dosage forms to enable the personalisation of treatment (Konta et al, 2017).…”