Manufacturing of hybrid drug delivery systems by utilizing the fused filament fabrication (FFF) technology

Figures & data

Table 1. Hybrid drug delivery systems that incorporate the FFF technology (ABS, acrylonitrile butadiene styrene; EC, ethyl cellulose; HPC, hydroxypropyl cellulose; HPMC, hydroxypropyl methylcellulose; HPMCAS, hydroxypropyl methylcellulose acetate succinate; PCL, poly – ε – caprolactone; PEO, polyethylene oxide; PLA, polylactic acid; PLLA, Poly L-lactic acid; PVA, poly(vinyl alcohol)).

Category	Filament type/origin	Active ingredient	Aim	Ref.
Manual Filling	PLA commercial	riboflavin	A gastric floating device with ease of manufacturing	[8]
	PVA, ABS commercial	metronidazole	A gastric floating device with constant drug release	[9]
	HPC, EC in-lab	theophylline	A gastric floating device with desirable lag time for pulsatile release	[10]
	PVA commercial	amoxicillin	A gastric floating device to provide prolonged drug release in the stomach	[11]
	PVA, PLA commercial	carbamazepine, halofantrine, saquinavir	Compartmental dosage forms with multiple active ingredients	[12]
	PVA, PLA commercial	isoniazid, rifampicin B	An anti-tuberculosis dual-compartmental device to modulate drug release	[13]
	PLA, PVA commercial, HPMC,HPMCAS in-lab	acetaminophen and dyes	Separate inner compartments forming a capsular device	[14]
	PVA commercial	dronedarone hydrochloride, ascorbic acid	Separate inner compartments providing predictable drug release profiles	[15]
	PVA commercial	progesterone	3D printed suppository molds for filling with different suppository formulations	[16]
	PLA commercial Eudragit L100-55 Eudragit S100	5-Fluorouracil	pH responsive for colonic targeting with controlled release	[17]
	HPMC phthalate in-lab	macromolecular dye	Gastroresistance, sustained release	[18]
	PVA commercial	lamivoudine, unknown proprietary Merck API	Flexibility in the form of the drug carrier	[20]
Automated/Manual Filling	PVA commercial	lamivoudine, unknown proprietary Merck API	Automation, one-step process printing and filling.	[20]
Automated Filling	Eudragit EPO, Eudragid RL in-lab	dipyridamole, theophyline	Instantaneous printing and filling of liquid capsules	[21]
	PLA commercial	anhydrous theophylline	A combinatorial system to produce colonic specific formulations	[22]
FFF/Electro-spinning	PCL (FFF apparatus)	heparin	Tubular scaffold reinforced with an outer layer	[23]
	PLLA commercial	osteocalcin, hydroxyapatite, type I collagen	Improvement of cell adhesion and proliferation	[24]
Other systems	PCL, PEO, Kollidon in-lab	hydrochlorothi–azide, lovastatin	Mass-customization, multi-drug loading and diverse release profiles	[25]
	HPC in-lab, PLA, PVA commercial	paracetamol	Measures to assure authenticity and tracking	[26]
	PVA, EC in-lab	diclofenac sodium	Utilization of commercial edible sheet in 3D printing as backing layer	[27]

Figure 1. Illustration of the potential of 3D printing for engineering drug release. The rows are representative examples of (from top to bottom): different tablet geometries (tablet length is denoted as L), their respective plots of normalized tablet width (w), and the experimental/theoretical data of drug release (blue/red dotted lines) corresponding to the different tablet shapes. Reprinted with permission from reference [19].

Figure 2. A conceptualized hybrid DDS with multiple chambers that provide immediate (blue), delayed (red), and sustained (green) release profiles of different APIs, as well as functional elements (white), e.g., mucoadhesive components, permeation enhancers, stabilizers, enzyme inhibitors and pH regulators.

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