Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics

Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient’s needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments’ properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented.

 

Download the full MDPI publication here: Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics or continue reading here: Pereira, G.G.; Figueiredo, S.; Fernandes, A.I.; Pinto, J.F. Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics. Pharmaceutics 2020, 12, 795.

Characteristics and thermal properties of the polymers used in hot-melt extrusion (HME)-coupled to FDM

Chemical Name of the PolymerTrade NameFDA ApprovedBiodegradable PolymerTm (°C)Tg (°C)Degradation Temperature (°C)
Polyvinyl alcohol (PVA)---YesYes---85---
Poly(vinylpyrrolidone) (PVP)
(MW 7000–11,000)Kollidon® 17 PFYesYes---140217
(MW 2000–3000)Kollidon® 12 PFYesYes---72196
Poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) (MW 45,000–70,000)Kollidon® VA64YesYes---105270
Poly(vinyl caprolactam-covinylacetate-ethylene glycol (MW 90,000–140,000)Soluplus®YesYes---72278
Hydroxypropyl cellulose (HPC)(MW 95,000)Klucel® LFYesYes---111227
Hydroxypropylmethyl cellulose (HPMC) (MW 25,000)Methocel™ K100LVYesYes168147259
Hydroxypropylmethyl cellulose (HPMC)(MW 150,000)Methocel™ K100MYesYes17396259
Hydroxypropyl methyl cellulose acetate succinate (HPMCAS)Affinisol™YesYes---115<250
Poly ethylene oxide (PEO)---YesYes100−67340
Poly(butyl methacrylate-co-(2-demethylamino ethyl) methacrylate-co-methyl methacrylate) 1:2:1Eudragit E PO®YesYes189–193 52250
Poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonio ethyl methacrylate chloride) 1:2:0.2Eudragit RL®YesYes---63166
Poly(methacrylic acid-co-methyl methacrylate) 1:1Eudragit L®YesYes---111176
Poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethylmethacrylate chloride) 1:2:0.1Eudragit RS®YesYes---64170
Poly(e-caprolactone) (PCLa)---YesYes60---310
Ethylene vinyl acetate (EVA)---YesYes7091300
Ethylcellulose (4 cPs)Ethocel® 4P168128200
Ethylcellulose (7 cPs)Ethocel® 7PYesYes168128205
Ethylcellulose (10 cPs)Ethocel® 10P172132205
Polyvinyl alcohol;polyethylene glycol graft copolymer (PVA:PEG)Kollicoat® IRYesYes---208200

 

Most common drugs used in FDM 3D printing and their characteristics

DrugBCS Class 1Therapeutic ClassMolecular Weight (g/mol)Melting Point (°C)Solubility at 37 °C (mg/mL)
4-Aminosalicylic acidIIAntitubercular agent153.141502
5-Aminosalicylic acidIVAnti-inflammatory153.1352750.1
AcetaminophenIAnti-inflammatory151.16170218
Amlodipine besylateIICalcium channel blocker408.881980.207
AmoxicillinIVAntibiotic365.41940.958
AripiprazoleIVAtypical antipsychotic448.381400.00777
Ascorbic acidIVitamin/Antioxidant176.12191330
BaclofenIIIGamma-aminobutyric acid agonist213.662070.712
BicalutamideIINon-steroidal anti-androgen430.371920.00928
BudesonideIICorticosteroid430.52260.0457
CaffeineIIBronchodilator or vasodilator194.1923411
CaptoprilIAngiotensin-converting-enzyme inhibitor217.29427160
CarvedilolIIAntihypertensive442.9114.50.00444
CiprofloxacinIVAntibiotic318.1581.81.35
Diclofenac sodiumIIAnti-inflammatory430.52850.00482
DomperidoneIIAntiemetic425.912420.986
Dronedarone hydrochlorideIIAntiarrhythmic556.761400.00201
DypyridamoleIIAntiplatelet drug504.631630.922
FelodipineIIAntihypertensive384.2647119.7
GlimepirideIIAntidiabetic490.622070.0384
GlipizideIIAntidiabetic445.532000.0164
HaloperidolIIAntipsychotic375.91480.00446
HydrochlorothiazideIIDiuretic297.742672.24
IbuprofenIIAnti-inflammatory206.293190.021
IndapamideIIAntihypertensive365.841610.0342
IndomethacinIIAnti-inflammatory357.81620.937
ItraconazoleIIAntifungal agent705.641660.00964
Lisinopril dihydrateIIIAntihypertensive405.491480.216
MetforminIIAntidiabetic129.161721.38
NitrofurantoinIIAntibiotic238.162250.415
PantoprazoleIIProton pump inhibitor383.371550.431
PrednisoloneICorticosteroid360.442300.24
QuinineIAntimalarial324.42570.334
RamiprilIIAntihypertensive416.51090.035
Rosuvastatin calciumIIAntihyperlipidemic481.541550.0886
TheophyllineIBronchodilator180.162705.5
WarfarinIAnticoagulant308.321610.0472
Keywords: extrudability; fused deposition modelling (FDM); hot-melt extrusion (HME); polymers; printability; three-dimensional printing
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