Skip to main content
Log in

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Kotreka UK, Adeyeye MC. Gastroretentive floating drug-delivery systems: a critical review. Crit Rev Ther Drug Carrier Syst. 2011;28(1):47–99.

    CAS  PubMed  Google Scholar 

  2. Prinderre P, Sauzet C, Fuxen C. Advances in gastro retentive drug-delivery systems. Expert Opin Drug Deliv. 2011;8(9):1189–203.

    CAS  PubMed  Google Scholar 

  3. Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm. 2016;510(1):144–58.

    CAS  PubMed  Google Scholar 

  4. Kaushik AY, Tiwari AK, Gaur A. Role of excipients and polymeric advancements in preparation of floating drug delivery systems. Int J Pharm Investig. 2015;5(1):1–12.

    PubMed  PubMed Central  Google Scholar 

  5. Sauzet C, Claeys-Bruno M, Nicolas M, Kister J, Piccerelle P, Prinderre P. An innovative floating gastro retentive dosage system: formulation and in vitro evaluation. Int J Pharm. 2009;378(1–2):23–9.

    CAS  PubMed  Google Scholar 

  6. Sungthongjeen S, Paeratakul O, Limmatvapirat S, Puttipipatkhachorn S. Preparation and in vitro evaluation of a multiple-unit floating drug delivery system based on gas formation technique. Int J Pharm. 2006;324(2):136–43.

    CAS  PubMed  Google Scholar 

  7. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opin Drug Deliv. 2006;3(2):217–33.

    CAS  PubMed  Google Scholar 

  8. Norman J, Madurawe RD, Moore CM, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.

    CAS  PubMed  Google Scholar 

  9. Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S, et al. 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Mol Pharm. 2015;12(11):4077–84.

    CAS  PubMed  Google Scholar 

  10. Okwuosa TC, Stefaniak D, Arafat B, Isreb A, Wan KW, Alhnan MA. A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res. 2016;33(11):2704–12.

    CAS  PubMed  Google Scholar 

  11. Kempin W, Franz C, Koster LC, Schneider F, Bogdahn M, Weitschies W, et al. Assessment of different polymers and drug loads for fused deposition modeling of drug loaded implants. Eur J Pharm Biopharm. 2017;115:84–93.

    CAS  PubMed  Google Scholar 

  12. Pere CPP, Economidou SN, Lall G, Ziraud C, Boateng JS, Alexander BD, et al. 3D printed microneedles for insulin skin delivery. Int J Pharm. 2018;544(2):425–32.

    CAS  PubMed  Google Scholar 

  13. Palo M, Hollander J, Suominen J, Yliruusi J, Sandler N. 3D printed drug delivery devices: perspectives and technical challenges. Expert Rev Med Devices. 2017;14(9):685–96.

    CAS  PubMed  Google Scholar 

  14. Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci. 2015;68:11–7.

    CAS  PubMed  Google Scholar 

  15. Goyanes A, Robles Martinez P, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494(2):657–63.

    CAS  PubMed  Google Scholar 

  16. Konta AA, Garcia-Pina M, Serrano DR. Personalised 3D printed medicines: which techniques and polymers are more successful? Bioengineering. 2017;4(4):79–96.

    PubMed Central  Google Scholar 

  17. Fu J, Yin H, Yu X, Xie C, Jiang H, Jin Y, et al. Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems. Int J Pharm. 2018;549(1–2):370–9.

    CAS  PubMed  Google Scholar 

  18. Huanbutta K, Sangnim T. Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology. J Drug Deliv Sci Technol. 2019;52:831–7.

    CAS  Google Scholar 

  19. Chai X, Chai H, Wang X, Yang J, Li J, Zhao Y, et al. Fused deposition modeling (FDM) 3D printed tablets for intragastric floating delivery of domperidone. Sci Rep. 2017;7(1):2829–38.

    PubMed  PubMed Central  Google Scholar 

  20. Fuenmayor E, Forde M, Healy AV, Devine DM, Lyons JG, McConville C, et al. Comparison of fused-filament fabrication to direct compression and injection molding in the manufacture of oral tablets. Int J Pharm. 2019;558:328–40.

    CAS  PubMed  Google Scholar 

  21. Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech. 2009;10(3):1071–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chaturvedi K, Umadevi S, Vaghani S. Floating matrix dosage form for propranolol hydrochloride based on gas formation technique: development and in vitro evaluation. Sci Pharm. 2010;78(4):927–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Maniruzzaman M, Morgan DJ, Mendham AP, Pang J, Snowden MJ, Douroumis D. Drug-polymer intermolecular interactions in hot-melt extruded solid dispersions. Int J Pharm. 2013;443(1–2):199–208.

    CAS  PubMed  Google Scholar 

  24. Arafat B, Wojsz M, Isreb A, Forbes RT, Isreb M, Ahmed W, et al. Tablet fragmentation without a disintegrant: a novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets. Eur J Pharm Sci. 2018;118:191–9.

    CAS  PubMed  Google Scholar 

  25. Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG. 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. J Drug Deliv Sci Technol. 2017;40:164–71.

    CAS  Google Scholar 

  26. Goyanes A, Buanz AB, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm. 2014;476(1–2):88–92.

    CAS  PubMed  Google Scholar 

  27. Tagami T, Fukushige K, Ogawa E, Hayashi N, Ozeki T. 3D printing factors important for the fabrication of polyvinylalcohol filament-based tablets. Biol Pharm Bull. 2017;40(3):357–64.

    CAS  PubMed  Google Scholar 

  28. Li Q, Wen H, Jia D, Guan X, Pan H, Yang Y, et al. Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. Int J Pharm. 2017;525(1):5–11.

    CAS  PubMed  Google Scholar 

  29. Madera-Santana TJ, Freile-Pelegrin Y, Azamar-Barrios JA. Physicochemical and morphological properties of plasticized poly(vinyl alcohol)-agar biodegradable films. Int J Biol Macromol. 2014;69:176–84.

    CAS  PubMed  Google Scholar 

  30. Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2015;89:157–62.

    CAS  PubMed  Google Scholar 

  31. Goyanes A, Scarpa M, Kamlow M, Gaisford S, Basit AW, Orlu M. Patient acceptability of 3D printed medicines. Int J Pharm. 2017;530(1–2):71–8.

    CAS  PubMed  Google Scholar 

  32. Smith DM, Kapoor Y, Klinzing GR, Procopio AT. Pharmaceutical 3D printing: design and qualification of a single step print and fill capsule. Int J Pharm. 2018;544(1):21–30.

    CAS  PubMed  Google Scholar 

  33. Melocchi A, Parietti F, Loreti G, Maroni A, Gazzaniga A, Zema L. 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. Journal of Drug Delivery Science and Technology. 2015;30:360–7.

    CAS  Google Scholar 

  34. Zare-Akbari Z, Farhadnejad H, Furughi-Nia B, Abedin S, Yadollahi M, Khorsand-Ghayeni M. PH-sensitive bionanocomposite hydrogel beads based on carboxymethyl cellulose/ZnO nanoparticle as drug carrier. Int J Biol Macromol. 2016;93(Pt A):1317–27.

    CAS  PubMed  Google Scholar 

  35. Farhadnejad H, Mortazavi SA, Erfan M, Darbasizadeh B, Motasadizadeh H, Fatahi Y. Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release. Int J Biol Macromol. 2018;111:696–705.

    CAS  PubMed  Google Scholar 

  36. Araujo MA, Cunha AM, Mota M. Changes on surface morphology of corn starch blend films. J Biomed Mater Res A. 2010;94(3):720–9.

    PubMed  Google Scholar 

  37. Mohsin M, Hossin A, Haik Y. Thermal and mechanical properties of poly(vinyl alcohol) plasticized with glycerol. J Appl Polym Sci. 2011;122(5):3102–9.

    CAS  Google Scholar 

  38. Srikanth MV, Rao NS, Sunil SA, Ram BJ, Kolapalli VRM. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharm Sin B. 2012;2(1):60–9.

    Google Scholar 

  39. Seema DM. Clay–polymer nanocomposites as a novel drug carrier: synthesis, characterization and controlled release study of propranolol hydrochloride. Appl Clay Sci. 2013;80–81:85–92.

    Google Scholar 

  40. Jan R, Habib A, Akram MA. Zia T-u-H, Khan AN. Uniaxial drawing of graphene-PVA nanocomposites: improvement in mechanical characteristics via strain-induced exfoliation of graphene. Nanoscale Res Lett. 2016;11(1):377–85.

    PubMed  PubMed Central  Google Scholar 

  41. Rezaei A, Tavanai H, Nasirpour A. Fabrication of electrospun almond gum/PVA nanofibers as a thermostable delivery system for vanillin. Int J Biol Macromol. 2016;91:536–43.

    CAS  PubMed  Google Scholar 

  42. Wang X, Wang XJ, Ching CB. Solubility, metastable zone width, and racemic characterization of propranolol hydrochloride. Chirality. 2002;14(4):318–24.

    CAS  PubMed  Google Scholar 

  43. Meka VS, Nali SR, Songa AS, Kolapalli VR. Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum). AAPS PharmSciTech. 2012;13(4):1451–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Palekar S, Nukala PK, Mishra SM, Kipping T, Patel K. Application of 3D printing technology and quality by design approach for development of age-appropriate pediatric formulation of baclofen. Int J Pharm. 2019;556:106–16.

    CAS  PubMed  Google Scholar 

  45. Verstraete G, Samaro A, Grymonpre W, Vanhoorne V, Van Snick B, Boone MN, et al. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes. Int J Pharm. 2018;536(1):318–25.

    CAS  PubMed  Google Scholar 

  46. Aho J, Botker JP, Genina N, Edinger M, Arnfast L, Rantanen J. Roadmap to 3D-printed oral pharmaceutical dosage forms: feedstock filament properties and characterization for fused deposition modeling. J Pharm Sci. 2019;108(1):26–35.

    CAS  PubMed  Google Scholar 

  47. Zhang J, Yang W, Vo AQ, Feng X, Ye X, Kim DW, et al. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: structure and drug release correlation. Carbohydr Polym. 2017;54:49–57.

    Google Scholar 

  48. Strubing S, Metz H, Mader K. Characterization of poly(vinyl acetate) based floating matrix tablets. J Control Release. 2008;126(2):149–55.

    PubMed  Google Scholar 

  49. Meka VS, Songa AS, Nali SR, Battu JR, Kolapalli VR. Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl. Investig Clin. 2012;53(1):60–70.

    Google Scholar 

  50. Gupta S, Webster TJ, Sinha A. Evolution of PVA gels prepared without crosslinking agents as a cell adhesive surface. J Mater Sci Mater Med. 2011;22(7):1763–72.

    CAS  PubMed  Google Scholar 

  51. Yang Y, Wang H, Li H, Ou Z, Yang G. 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release. Eur J Pharm Sci. 2018;115:11–8.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Guang-Rong Yan or Tian-Yuan Fan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, D., Xu, XY., Li, R. et al. Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages. AAPS PharmSciTech 21, 6 (2020). https://doi.org/10.1208/s12249-019-1521-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1521-x

KEY WORDS

Navigation