Additive manufacturing (AM) is an emerging pharmaceutical manufacturing technique feasible for patient-centric personalised medicine with tailored pharmacotherapy. Fused filament fabrication (FFF) is a highly emphasised 3D printing technology because it is highly economical and user friendly. However, bridging fused filament fabrication with hot-melt extrusion for filament synthesis is one of the crucial steps involved. This study highlights the feasibility of prototyping a diclofenac sodium-filled enteric hollow compartmental device to avoid gastric irritation associated with the drug. Furthermore, for the first time Kollicoat MAE100P was evaluated for its extrudability in hot-melt and printability during fused filament fabrication. A novel hollow compartmental device was designed with improved sealing conditions, unlike conventional capsules. An optimistic printable filament was extruded using triethyl citrate (TEC) and talc as plasticiser and filler, respectively. The thermal and chemical stabilities of the polymers were confirmed by DSC and FTIR analyses, respectively. The final layer-by-layer printed drug-filled hollow compartmental device was evaluated for its morphology and in vitro enteric release behaviour at pH 6.8, showing a complete release within 4 h with a lag period in an acidic environment of pH 1.2 and the release kinetics fit well with first-order kinetics (R2 > 0.9522). The gastric resistance of the hollow compartmental device was confirmed by in vivo pharmacokinetic assessment, which revealed a 30-min lag phase of the drug release and obtained PK parameters compiles for the delayed release phenomenon. This study revealed the possibility of fabricating a hollow compartmental device with an improved sealing effect using Kollicoat MAE100P by combining FFF with the melt extrusion process. The results showed that the designed hollow compartmental device provided intestinal release, successfully bypassing release in an acidic environment.
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Harvey A et al (2012) The future of technologies for personalised medicine. New Biotechnol 29(6):625–633. https://doi.org/10.1016/j.nbt.2012.03.009
Chen G, Xu Y, Kwok PCL, Kang L (2020) Pharmaceutical applications of 3D printing. Addit Manuf 34:101209
Ozyilmaz ED, Turan A, Comoglu T (2021) An overview on the advantages and limitations of 3D printing of microneedles. Pharm Dev Technol 26(9):923–933. https://doi.org/10.1080/10837450.2021.1965163
A. Standard, “Standard terminology for additive manufacturing technologies,” ASTM Int. F2792–12a, 2012.
Xu X et al (2021) “Smartphone-enabled 3D printing of medicines. Int J Pharm 609:121199. https://doi.org/10.1016/j.ijpharm.2021.121199
Ibrahim M et al (2019) 3D printing of metformin HCl PVA tablets by fused deposition modeling: drug loading, tablet design, and dissolution studies. AAPS PharmSciTech 20(5):1–11
Mwema FM, Akinlabi ET (2020) Basics of fused deposition modelling (FDM). in Fused Deposition Modeling: Strategies for Quality Enhancement, F. M. Mwema and E. T. Akinlabi, Eds. Cham: Springer International Publishing, 2020, pp. 1–15. doi: https://doi.org/10.1007/978-3-030-48259-6_1.
Repka MA et al (2018) Melt extrusion with poorly soluble drugs—An integrated review. Int J Pharm 535(1):68–85. https://doi.org/10.1016/j.ijpharm.2017.10.056
Kallakunta VR, Sarabu S, Bandari S, Tiwari R, Patil H, Repka MA (2019) An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I. Expert Opin Drug Deliv 16(5):539–550. https://doi.org/10.1080/17425247.2019.1609448
Butreddy A et al (2022) Hot-melt extruded hydroxypropyl methylcellulose acetate succinate based amorphous solid dispersions: Impact of polymeric combinations on supersaturation kinetics and dissolution performance. Int J Pharm 615:121471. https://doi.org/10.1016/j.ijpharm.2022.121471
Zema L, Melocchi A, Maroni A, Gazzaniga A (2017) Three-dimensional printing of medicinal products and the challenge of personalized therapy. J Pharm Sci 106(7):1697–1705
Altman R, Bosch B, Brune K, Patrignani P, Young C (2015) Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs 75(8):859–877. https://doi.org/10.1007/s40265-015-0392-z
Jeganathan B, Prakya V, Deshmukh A (2016) Preparation and evaluation of diclofenac sodium tablet coated with polyelectrolyte multilayer film using hypromellose acetate succinate and polymethacrylates for pH-dependent, modified release drug delivery. AAPS PharmSciTech 17(3):578–587. https://doi.org/10.1208/s12249-015-0385-y
Arany P et al (2020) In vitro tests of FDM 3D-printed diclofenac sodium-containing implants. Molecules 25:24. https://doi.org/10.3390/molecules25245889
Nollenberger K, Albers J (2013) Poly(meth)acrylate-based coatings. Int J Pharm 457(2):461–469. https://doi.org/10.1016/j.ijpharm.2013.09.029
Kapoor D, Maheshwari R,Verma K, Sharma S, Ghode P, Tekade RK (2020) “Chapter 14—Coating technologies in pharmaceutical product development,” in Drug Delivery Systems, R. K. Tekade, Ed. Academic Press, 2020, pp. 665–719. doi: https://doi.org/10.1016/B978-0-12-814487-9.00014-4.
Nober C et al (2019) Feasibility study into the potential use of fused-deposition modeling to manufacture 3D-printed enteric capsules in compounding pharmacies. Int J Pharm 569:118581. https://doi.org/10.1016/j.ijpharm.2019.118581
Eleftheriadis GK, Katsiotis CS, Bouropoulos N, Koutsopoulos S, Fatouros DG (2020) FDM-printed pH-responsive capsules for the oral delivery of a model macromolecular dye. Pharm Dev Technol 25(4):517–523. https://doi.org/10.1080/10837450.2019.1711396
“Capsule Sizes,” Nutraceuticals Group Europe. https://nutraceuticalsgroup.com/uk/tools/capsule-sizes/ (Accessed Jan. 03, 2022).
Feuerbach T, Kock S, Thommes M (2020) Slicing parameter optimization for 3D printing of biodegradable drug-eluting tracheal stents. Pharm Dev Technol 25(6):650–658. https://doi.org/10.1080/10837450.2020.1727921
Mendyk A, Jachowicz R (2007) Unified methodology of neural analysis in decision support systems built for pharmaceutical technology. Expert Syst Appl 32(4):1124–1131. https://doi.org/10.1016/j.eswa.2006.02.019
Choudhury D, Jala A, Murty US, Borkar RM, Banerjee S (2022) In vitro and in vivo evaluations of berberine-loaded microparticles filled in-house 3D printed hollow capsular device for improved oral bioavailability. AAPS PharmSciTech 23(4):89. https://doi.org/10.1208/s12249-022-02241-9
Malakar TK, Chaudhari VS, Dwivedy SK, Murty US, Banerjee S (2021) “3D printed housing devices for segregated compartmental delivery of oral fixed-dose anti-tubercular drugs adopting print and fill strategy”, 3D Print. Addit Manuf. https://doi.org/10.1089/3dp.2021.0037
“USP Monographs: Diclofenac Sodium.” http://www.pharmacopeia.cn/v29240/usp29nf24s0_m24962.html (Accessed May 16, 2022).
Yong CS et al (2005) Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats. Int J Pharm 301(1–2):54–61. https://doi.org/10.1016/j.ijpharm.2005.05.037
Okwuosa TC, Pereira BC, Arafat B, Cieszynska M, Isreb A, Alhnan MA (2017) Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm Res 34(2):427–437. https://doi.org/10.1007/s11095-016-2073-3
Choudhury D, Murty US, Banerjee S (2021) 3D printing and enteric coating of a hollow capsular device with controlled drug release characteristics prepared using extruded Eudragit® filaments. Pharm Dev Technol. 26(9)P:1010–1020, 2021, doi: https://doi.org/10.1080/10837450.2021.1970765
“Talc – Database of ATR-FT-IR spectra of various materials.” https://spectra.chem.ut.ee/paint/fillers/talc/ (Accessed Jan. 05, 2022)
Lim H, Hoag SW (2013) Plasticizer effects on physical-mechanical properties of solvent cast Soluplus® Films. AAPS PharmSciTech 14(3):903–910. https://doi.org/10.1208/s12249-013-9971-z
Pereira GG, Figueiredo S, Fernandes AI, Pinto JF (2020) Polymer selection for hot-melt extrusion coupled to fused deposition modelling in pharmaceutics. Pharmaceutics. https://doi.org/10.3390/pharmaceutics12090795
Ray S et al (2010) Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation. Drug Deliv 17(7):508–519. https://doi.org/10.3109/10717544.2010.483256
Arifin DY, Lee LY, Wang C-H (2006) Mathematical modeling and simulation of drug release from microspheres: IMPLICATIONS to drug delivery systems. Adv Drug Deliv Rev 58(12):1274–1325. https://doi.org/10.1016/j.addr.2006.09.007
Ritger PL, Peppas NA (1987) A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Controlled Release 5(1):23–36. https://doi.org/10.1016/0168-3659(87)90034-4
Suryavanshi P, Chaudhari VS, Banerjee S (2022) Customized 3D-printed hollow capsular device filled with norfloxacin-loaded micropellets for controlled-release delivery. Drug Deliv Transl Res. https://doi.org/10.1007/s13346-022-01198-3
Polli JE, Crison JR, Amidon GL (1996) Novel approach to the analysis of in vitro-in vivo relationships. J Pharm Sci 85(7):753–760. https://doi.org/10.1021/js9503587
The authors are thankful to the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, for providing the necessary funding support.
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Kotha, S.L.R., Adye, D.R., Borkar, R.M. et al. 3D printing of hollow capsular body & sealing pin by fused filament fabrication (FFF) technique using Kollicoat MAE 100P filament for intestinal specific delivery. J Mater Sci 58, 9282–9296 (2023). https://doi.org/10.1007/s10853-023-08598-x