The ability to customize products with additive manufacturing allows manufacturers to meet the unique requirements and functionality for individual applications. By printing dissolvable materials as a matrix material, the release of active agents over time can be tailored on a per part basis by varying both geometry and printed material properties. Direct printing of actives via filament material extrusion is challenging because many active agents become inactive at the elevated temperatures found in the melt-based process. This limitation is circumvented by in situ embedding the active agents into a priori designed voids of a printed water-soluble capsule. In this work, this process is demonstrated by the in situ deposition of liquids and powders into thin-walled, water-soluble, printed structures. The authors demonstrate the ability to tune dissolution time by varying the thickness of a printed part’s walls in order to create a delay in release and by creating parts with multiple chambers to initiate a multistaged release. This ability provides opportunities for creating customized containers for the prescribed release of liquid and powdered active agents.
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References
1.
BhatiaSK, HarvardU, SharmaS. Massachusetts I of T. 3D-Printed Prosthetics Roll Off the Presses. American Institute of Chemical Engineers; 2014;(May).
2.
ChungKS, ShinDA, KimKN, et al.Vertebral reconstruction with customized 3-dimensional−printed spine implant replacing large vertebral defect with 3-year follow-up. World Neurosurg, 2019; 126:90–95; doi: 10.1016/j.wneu.2019.02.020
3.
ChartrainNA, WilliamsCB, WhittingtonAR. A review on fabricating tissue scaffolds using vat photopolymerization. Acta Biomater, 2018; 74:90–111; doi: 10.1016/j.actbio.2018.05.010
4.
SadiaM, SośnickaA, ArafatB, et al.Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. Int J Pharm, 2016; 513(1–2):659–668; doi: 10.1016/j.ijpharm.2016.09.050
5.
OkwuosaTC, StefaniakD, ArafatB, et al.A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res, 2016; 33(11):2704–2712; doi: 10.1007/s11095-016-1995-0
6.
MelocchiA, PariettiF, MaroniA, et al.Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int J Pharm, 2016; 509(1–2):255–263; doi: 10.1016/j.ijpharm.2016.05.036
7.
GoyanesA, ChangH, SedoughD, et al.Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. Int J Pharm, 2015; 496(2):414–420; doi: 10.1016/j.ijpharm.2015.10.039
8.
PietrzakK, IsrebA, AlhnanMA. A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharm Biopharm, 2015; 96:380–387; doi: 10.1016/j.ejpb.2015.07.027
9.
KatstraWE, PalazzoloRD, RoweCW, et al.Oral dosage forms fabricated by three dimensional printing E. J Control Release, 2000; 66(1):1–9.
10.
KhaledSA, BurleyJC, AlexanderMR, et al.3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. J Control Release, 2015; 217:308–314; doi: 10.1016/j.jconrel.2015.09.028
11.
KhaledSA, BurleyJC, AlexanderMR, et al.Desktop 3D printing of controlled release pharmaceutical bilayer tablets. Int J Pharm, 2014; 461(1–2):105–111.
12.
SkowyraJ, PietrzakK, AlhnanMA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci, 2015; 68:11–17; doi: 10.1016/j.ejps.2014.11.009
13.
WursterD, SeitzJ. Investigation of drug release from solids III: Effect of a changing surface-weight ratio on the dissolution rate. J American Pharmaceutical, 1960; 49(6):335–338.
14.
WuW, ZhengQ, GuoX, et al.A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy. Biomed Mater, 2009; 4(6):65005; doi: 10.1088/1748-6041/4/6/065005
15.
GoyanesA, WangJ, BuanzA, et al.3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. Mol Pharm, 2015; 12(11):4077–4084; doi: 10.1021/acs.molpharmaceut.5b00510
16.
Billy DunnMD. NDA Approval 207958. 2015; doi: Reference ID: 3800218
17.
GuptaMK, MengF, JohnsonBN, et al.3D printed programmable release capsules. Nano Lett, 2015; 15(8):5321–5329; doi: 10.1021/acs.nanolett.5b01688
18.
KarasuluHY, ErtanG. Different geometric shaped hydrogel theophylline tablets: Statistical approach for estimating drug release. Farmaco, 2003; 57(11):939–945; doi: 10.1016/S0014-827X(02)01297-1
19.
GoyanesA, RoblesP, BuanzA, et al.Effect of geometry on drug release from 3D printed tablets. Int J Pharm, 2015; 494(2):657–663; doi: 10.1016/j.ijpharm.2015.04.069
20.
GoyanesA, BuanzABM, BasitAW, et al.Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm, 2014; 476(1–2):88–92; doi: 10.1016/j.ijpharm.2014.09.044
21.
ChengK, ZhuJ, SongX, et al.Studies of hydroxypropyl methylcellulose donut-shaped tablets. Drug Dev Ind Pharm, 1999; 25(9):1067–1071; doi: 10.1081/DDC-100102271
22.
ZhouY, WuXY. Finite element analysis of diffusional drug release from complex matrix systems. I. Complex geometries and composite structures 1. J Controlled Release, 1997; 49(2–3):277–288.
23.
CleaveJP. Some geometrical considerations concerning the design of tablets. J Pharm Pharmacol, 1965; 17(11):698–702; doi: 10.1111/j.2042-7158.1965.tb07591.x
24.
LeeBK, HeeY, SukJ, et al.Fabrication of drug-loaded polymer microparticles with arbitrary geometries using a piezoelectric inkjet printing system. Int J Pharm, 2012; 427(2):305–310; doi: 10.1016/j.ijpharm.2012.02.011
25.
SunY, SohS. Printing tablets with fully customizable release profi les for personalized medicine. Adv Mater, 2015; 27(47):7847–7853; doi: 10.1002/adma.201504122
26.
GoyanesA, BuanzABM, HattonGB, et al.3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm, 2015; 89:157–162; doi: 10.1016/j.ejpb.2014.12.003
27.
ZawaskiC, MargarettaE, StevensonA, et al.Embedding of Liquids into Water Soluble Materials via Additive Manufacturing for Timed Release. Solid Freeform Fabrication Proceedings, 2017:2047–2059.
28.
OkwuosaTC, SoaresC, GollwitzerV, et al.On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing. Eur J Pharm Sci, 2018; 118(February):134–143; doi: 10.1016/j.ejps.2018.03.010
29.
SchmitzM, LeisterA, DezfuliN, et al.Liquido: Embedding liquids into 3D printed objects to sense tilting and motion. Conference on Human Factors in Computing Systems - Proceedings 2016;07-12-May-:2688–2696; 2016; doi: 10.1145/2851581.2892275
30.
MelocchiA, PariettiF, LoretiG, et al.3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. J Drug Deliv Sci Technol, 2015; 30:360–367; doi: 10.1016/j.jddst.2015.07.016
31.
OkwuosaTC, PereiraBC, ArafatB, et al.Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm Res, 2017; 34(2):427–437; doi: 10.1007/s11095-016-2073-3
32.
MaroniA, MelocchiA, PariettiF, et al.3D printed multi-compartment capsular devices for two-pulse oral drug delivery. J Control Release, 2017; 268(October):10–18; doi: 10.1016/j.jconrel.2017.10.008
33.
MoonA, KashyaP, TakdhatP, et al.Formulation and In-Vitro characterization of calcitriol soft gelatin capsule. World J Pharm Res, 2018; 7(5):1590–1612; doi: 10.20959/wjpr20185-11346
34.
MeiselNA, ElliottAM, WilliamsCB. A procedure for creating actuated joints via embedding shape memory alloys in PolyJet 3D printing. J Intell Mater Syst Struct, 2015; 26(12):1498–1512; doi: 10.1177/1045389X14544144
35.
EspalinD, MuseDW, MacDonaldE, et al.3D Printing multifunctionality: Structures with electronics. Int J Adv Manuf Technol, 2014; 72(5–8):963–978; doi: 10.1007/s00170-014-5717-7
36.
GaikwadAM, WhitingGL, SteingartDA, et al.Highly flexible, printed alkaline batteries based on mesh-embedded electrodes. Adv Mater, 2011; 23(29):3251–3255; doi: 10.1002/adma.201100894
37.
IyerV, ChanJ, GollakotaS. 3D printing wireless connected objects. ACM Trans Graph, 2017; 36(6):1–13; doi: 10.1145/3130800.3130822
38.
DutyC, AjinjeruC, KishoreV, et al.A viscoelastic model for evaluating extrusion-based print conditions. Solid Freeform Fabrication Symposium 2017; 495–506.
39.
GordeevEG, GalushkoAS, AnanikovVP. Improvement of quality of 3D printed objects by elimination of microscopic structural defects in fused deposition modeling. PLoS One, 2018; 13(6):e0198370; doi: 10.1371/journal.pone.0198370
40.
SinhaS, MeiselNA. Influence of Embedding Process on Mechanical Properties of Material Extrusion Parts. Solid Freeform Fabrication 2016, 2016:847–863.
41.
MatosBDM, RochaV, da SilvaEJ, et al.Evaluation of commercially available polylactic acid (PLA) filaments for 3D printing applications. J Therm Anal Calorim, 2019; 137(2):555–562; doi: 10.1007/s10973-018-7967-3
42.
SeppalaJE, Hoon HanS, HillgartnerKE, et al.Weld formation during material extrusion additive manufacturing. Soft Matter, 2017; 13(38):6761–6769; doi: 10.1039/C7SM00950J
43.
ZaldivarRJ, WitkinDB, McLouthT, et al.Influence of processing and orientation print effects on the mechanical and thermal behavior of 3D-Printed ULTEM® 9085 Material. Addit Manuf, 2017; 13:71–80; doi: 10.1016/j.addma.2016.11.007
44.
RippieEG, JohnsonJR. Regulation of dissolution rate by pellet geometry. J Pharm Sci, 1969; 58(4):428–431.
