Skip to main content
Log in

3D Printed “Starmix” Drug Loaded Dosage Forms for Paediatric Applications

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print “candy – like” formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability.

Methods

Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug – excipient interactions and the content uniformity.

Results

Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min.

Conclusions

3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.

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

Access this article

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
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

DSC:

Differential scanning calorimetry

FT-IR:

Fourier Transform Infra-red Spectroscopy

HME:

Hot melt extrusion processing

HPLC:

High performance liquid chromatography

HPMCAS:

Hypromellose acetate succinate

IND:

Indomethacin

PEG:

Polyethylene glycol

SEM:

Scanning Electron Microscopy

TGA:

Thermogravimetric analysis

XRPD:

X-ray powder diffraction

References

  1. Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric drugs—a review of commercially available oral formulations. J Pharm Sci. 2008;97:1731–74.

    Article  CAS  PubMed  Google Scholar 

  2. Formulations of choice for the paediatric population. European Medicines Agancy (2006). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf.

  3. Lopez FL, Ernest TB, Tuleu C, Gul MO. Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms. Expert Opin Drug Deliv. 2015;12:1727–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Benavides S, Huynh D, Morgan J, Briars L. Approach to the pediatric prescription in a community pharmacy. J Pediatr Pharmacol Ther. 2011;16(4):298–307.

    PubMed  PubMed Central  Google Scholar 

  5. Yin HS, Mendelsohn AL, Wolf MS, Parker RM, Fierman A, van Schaick L, et al. Parents' medication administration errors: role of dosing instruments and health literacy. Arch Pediatr Adolesc Med. 2010;164:181–6.

    Article  PubMed  Google Scholar 

  6. Mennella JA, Roberts KM, Mathew PS, Reed DR. Children’s perceptions about medicines: individual differences and taste. BMC Pediatr. 2015;15:130.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Turner MA, Catapano M, Hirschfeld S, Giaquinto C. Paediatric drug development: The impact of evolving regulations. Adv Drug Deliv Rev. 2014;73:2–13.

    Article  CAS  PubMed  Google Scholar 

  8. Alhnan MA, Okwuosa TC, Sadia M, Wan KW, Ahmed W, Arafat B. Emergence of 3D printed dosage forms: Opportunities and challenges. Pharm Res. 2016;33(8):1817–32.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Sandler N, Preis M. Printed drug-delivery systems for improved patient treatment. Trends Pharmacol Sci. 2016;37(12):1070–80.

    Article  CAS  PubMed  Google Scholar 

  11. Preis M, Öblom H. 3D-printed drugs for children-Are we ready yet? AAPS Pharm SciTech. 2017;18(2):303–8.

    Article  Google Scholar 

  12. Sachs E, Cima M, Cornie J. Three-dimensional printing: rapid tooling and prototypes directly from a CAD model. CIRP Ann Manuf, Techn. 1990;39:201–4.

    Article  Google Scholar 

  13. Khaled SA, Burley JC, Alexander MR, Roberts CR. Desktop 3D printing of controlled release pharmaceutical bilayer tablets. Int J Pharm. 2014;461:105–11.

    Article  CAS  PubMed  Google Scholar 

  14. Goyanes A, Chang H, Sedough D, Hatton GB, Wang J, Buanz A, et al. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. Int J Pharm. 2015;496:414–20.

    Article  CAS  PubMed  Google Scholar 

  15. Water JJ, Bohr A, Boetker J, Aho J, Sandler N, Nielsen HM, et al. Three-dimensional printing of drug-eluting implants: Preparation of an antimicrobial polylactide feedstock material. J Pharm Sci. 2015;104:1099–107.

    Article  CAS  PubMed  Google Scholar 

  16. Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. J Control Release. 2015;217:308–14.

    Article  CAS  PubMed  Google Scholar 

  17. Goyanes A, Det-Amornrat U, Wang J, Basit AW, Gaisford S. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J Control Release. 2016;234:41–8.

    Article  CAS  PubMed  Google Scholar 

  18. Busch SF, Weidenbach M, Fey M, Schäfer F, Probst T, Koch M. Optical properties of 3D printable plastics in the THz regime and their application for 3D printed THz optics. J Infrared Millim Terahertz Waves. 2014;35:993–7.

    Article  CAS  Google Scholar 

  19. Goyanes A, Buanz A, 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.

    Article  CAS  PubMed  Google Scholar 

  20. Goyanes A, Martinez PR, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharma. 2015;494:657–63.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Maniruzzaman M, Boateng JB, Bonnefille M, Aranyos A, Mitchell JC, Douroumis D. Taste masking of paracetamol by hot-melt extrusion: An in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2012;80:433–42.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Genina N, Holländer J, Jukarainen H, Mäkilä E, Salonen J, Sandler N. Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. Eur J Pharm Sci. 2015;30(90):53–63.

    Google Scholar 

  26. Melocchi A, Parietti F, Maroni A, Foppoli A, Gazzaniga A, Zema L. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modelling. Int J Pharm. 2016;509:255–63.

    Article  CAS  PubMed  Google Scholar 

  27. Boetker J, Water JJ, Aho J, Arnfast L, Bohr A, Rantanen J. Modifying release characteristics from 3D printed drug-eluting products. Eur J Pharm Sci. 2016;90:47–52.

    Article  CAS  PubMed  Google Scholar 

  28. El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi Pharm J. 2009;17:217–25.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhang G-C, Lin H-L, Lin S-Y. Thermal analysis and FTIR spectral curve-fitting investigation of formation mechanism and stability of indomethacin-saccharin cocrystals via solid-state grinding process. J Pharm Biomed Anal. 2012;66:162–9.

    Article  CAS  PubMed  Google Scholar 

  30. Lim RTY, Ng WK, Tan RB. Dissolution enhancement of indomethacin via amorphization using co-milling and supercritical co-precipitation processing. Powder Tech. 2013;240:79–87.

    Article  CAS  Google Scholar 

  31. Bandi N, Wei W, Roberts CB, Kotra LP, Kompella UB. Preparation of budesonide–and indomethacin–hydroxypropyl-β-cyclodextrin (HPBCD) complexes using a single-step, organic-solvent-free supercritical fluid process. Eur J Pharm Sci. 2004;23:159–68.

    Article  CAS  PubMed  Google Scholar 

  32. Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and Indomethacin in Amorphous molecular dispersions. Pharm Res. 1997;14:1691–8.

    Article  CAS  PubMed  Google Scholar 

  33. Ewing AV, Clarke GS, Kazarian SG. Stability of indomethacin with relevance to the release from amorphous solid dispersions studied with ATR-FTIR spectroscopic imaging. Eur J Pharm Sci. 2014;60:64–71.

    Article  CAS  PubMed  Google Scholar 

  34. Chauhan H, Kuldipkumar A, Barder T, Medek A, Gu C-H, Atef E. correlation of inhibitory effects of polymers on Indomethacin precipitation in solution and amorphous solid crystallization based on molecular interaction. Pharm Res. 2014;31:500–15.

    Article  CAS  PubMed  Google Scholar 

  35. Walsh J, Cram A, Woertz K, Breitkreutz J, Winzenburg G, Turner R, et al. E.F. Initiative, Playing hide and seek with poorly tasting paediatric medicines: do not forget the excipients. Adv Drug Deliv Rev. 2014;73:14–33.

    Article  CAS  PubMed  Google Scholar 

  36. Maniruzzaman M, Boateng JS, Chowdhry BZ, Snowden MJ, Douroumis D. A review on the taste masking of bitter APIs: hot-melt extrusion (HME) evaluation. Drug Dev Ind Pharm. 2014;40:145–56.

    Article  CAS  PubMed  Google Scholar 

  37. Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D. Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion. Colloids Surf B: Biointerfaces. 2011;86:275–84.

    Article  CAS  PubMed  Google Scholar 

  38. Rachid Q, Rawas-Qalaji M, Estelle F, Simons R, Simons KJ. Dissolution testing of sublingual tablets: A novel In vitro method. AAPS PharmSciTech. 2011;12(2):544–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dennis Douroumis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scoutaris, N., Ross, S.A. & Douroumis, D. 3D Printed “Starmix” Drug Loaded Dosage Forms for Paediatric Applications. Pharm Res 35, 34 (2018). https://doi.org/10.1007/s11095-017-2284-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-017-2284-2

Key Words

Navigation