Skip to main content

Advertisement

SpringerLink
Log in

A Smart Interface for Reliable Intradermal Injection and Infusion of High and Low Viscosity Solutions

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

ABSTRACT

Purpose

We present a smart intradermal interface suitable for skin-attached drug delivery devices. Our solution enables injections or infusions that are less invasive compared to subcutaneous injections and are leakage-free at the location of penetration.

Methods

The intradermal interface is based on a 31-gauge cannula embedded in a slider, movable relative to a carrier plate that can easily be fixed onto the skin. By simply pushing the slider, the cannula is inserted into the dermis.

Results

We performed injections and infusions with stained water and polyethylene glycol (PEG) solution in ex vivo pig skin. The sizes of coloured spots in the skin range from 3.5 mm2 to 15.4 mm2 for stained water depending on the infused volume. Infusing stained PEG solution resulted in stained tissue areas about one order of magnitude larger. One of three investigated leakage modes is unacceptable but can be reliably avoided by proper site selection. At low flow rates and at the beginning of an infusion an initial back pressure overshoot was identified. This effect was identified as the limiting parameter for the design of small programmable or intelligent devices based on micro actuators.

Conclusions

With the proposed easy-to-use interface, intradermal injections and infusions can be performed reliably. Therefore, it is supposed to be an ideal and clinically relevant solution for self-administration of parenteral drugs in home care applications.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

Notes

  1. Overview Brochure Carbowax PEG, The Dow Chemical Company, Midland, Michigan, USA

  2. According to the subsequent text the time constant of the experimental setup including the tissue can be calculated to be 0.7 min, with Rtotal,0.50 ml/h = 62 kPa h/ml (calculated with data of Table IV) and Csetup = 0.2 μl/kPa (see subsequent text).

REFERENCES

  1. Holland D, Booy R, De Looze F, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J Infect Dis. 2008;198:650–8.

    Article  PubMed  Google Scholar 

  2. Laurent PE, Bonnet S, Alchas P, Regolini P, Mikszta JA, Pettis R, et al. Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system. Vaccine. 2007;25:8833–42.

    Article  CAS  PubMed  Google Scholar 

  3. Van Damme P, Oosterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine. 2009;27:454–9.

    Article  PubMed  Google Scholar 

  4. Gupta J, Felner EI, Prausnitz MR. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol Ther. 2009;11:329–37.

    Article  CAS  PubMed  Google Scholar 

  5. Cross S, Roberts M. Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development? Curr Drug Deliv. 2004;1:81–92.

    Article  CAS  PubMed  Google Scholar 

  6. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26:1261–8.

    Article  CAS  PubMed  Google Scholar 

  7. Banga AK. Microporation applications for enhancing drug delivery. Expert Opin Drug Deliv. 2009;6:343–54.

    Article  CAS  PubMed  Google Scholar 

  8. Gardeniers HJGE, Luttge R, Berenschot EJW, de Boer MJ, Yeshurun SY, Hefetz M, et al. Silicon micromachined hollow microneedles for transdermal liquid transport. J Microelectromech Syst. 2003;12:855–62.

    Article  Google Scholar 

  9. Griss P, Stemme G. Side-opened out-of-plane microneedles for microfluidic transdermal liquid transfer. J Microelectromech Syst. 2003;12:296–301.

    Article  Google Scholar 

  10. Stoeber B, Liepmann D. Arrays of hollow out-of-plane microneedles for drug delivery. J Microelectromech Syst. 2005;14:472–9.

    Article  Google Scholar 

  11. Martanto W, Moore JS, Kashlan O, Kamath R, Wang PM, O’Neal JM, et al. Microinfusion using hollow microneedles. Pharm Res. 2006;23:104–13.

    Article  CAS  PubMed  Google Scholar 

  12. Khumpuang S, Horade M, Fujioka K, Sugiyama S. Geometrical strengthening and tip-sharpening of a microneedle array fabricated by X-ray lithography. Microsyst Technol. 2007;13:209–14.

    Article  CAS  Google Scholar 

  13. Bodhale D, Nisar A, Afzulpurkar N. Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications. Microfluid_Nanofluid. 2010;8:373–92.

    Article  CAS  Google Scholar 

  14. Kim K, Park DS, Lu HM, Che W, Kim K, Lee JB, et al. A tapered hollow metallic microneedle array using backside exposure of SU-8. J Micromech Microeng. 2004;14:597–603.

    Article  CAS  Google Scholar 

  15. Verbaan FJ, Bal SM, van den Berg DJ, Dijksman JA, van Hecke M, Verpoorten H, et al. Improved peircing of microneedle arrays in dermatomed human skin by an impact insertion method. J Control Release. 2008;128:80–8.

    Article  CAS  PubMed  Google Scholar 

  16. Verbaan FJ, Bal SM, van den Berg DJ, Groenink WHH, Verpoorten H, Lüttge R, et al. Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. J Control Release. 2007;117:238–45.

    Article  CAS  PubMed  Google Scholar 

  17. Heinemann L, Pettis RJ, Hirsch LJ, Nosek L, Kapitza C, Sutter DE, et al. Microneedle-based intradermal injection of lispro or human regular insulin accelerates insulin uptake and reduces post-prandial glycaemia. Diabetologia. 2009;52:963.

    Google Scholar 

  18. Donnelly RF, Singh TRR, Tunney MM, Morrow DIJ, McCarron PA, O’Mahony C, et al. Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro. Pharm Res. 2009;26:2513–22.

    Article  CAS  PubMed  Google Scholar 

  19. Häfeli UO, Mokhtari A, Liepmann D, Stoeber B. In vivo evaluation of a microneedle-based miniature syringe for intradermal drug delivery. Biomed Microdevices. 2009;11:943–50.

    Article  Google Scholar 

  20. Nisar A, AftuIpurkar N, Mahaisavariya B, Tuantranont A. MEMS-based micropumps in drug delivery and biomedical applications. Sens Actuat B Chem. 2008;130:917–42.

    Article  Google Scholar 

  21. Matteucci M, Casella M, Bedoni M, Donetti E, Fanetti M, De Angelis F, et al. A compact and disposable transdermal drug delivery system. Microelectron Eng. 2008;85:1066–73.

    Article  CAS  Google Scholar 

  22. Lemmer B. Chronobiology, drug-delivery, and chronotherapeutics. Adv Drug Deliv Rev. 2007;59:825–7.

    Article  CAS  PubMed  Google Scholar 

  23. Iverson BD, Garimella SV. Recent advances in microscale pumping technologies: a review and evaluation. Microfluid Nanofluid. 2008;5:145–74.

    Article  CAS  Google Scholar 

  24. Henning A, Neumann D, Kostka KH, Lehr CM, Schaefer UF. Influence of human skin specimens consisting of different skin layers on the result of in vitro permeation experiments. Skin Pharmacol Physiol. 2008;21:81–8.

    Article  CAS  PubMed  Google Scholar 

  25. Sepassi K, Yalkowsky SH. Solubility prediction in octanol: a technical note. AAPS PharmSciTech. 2006;7:E26.

    Article  PubMed  Google Scholar 

  26. Yamaoka T, Tabata Y, Ikada Y. Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous adminsitration to mice. J Pharm Sci-US. 1994;83:601–8.

    Article  CAS  Google Scholar 

  27. Santhanalaksmi J, Balaji S. Binding studies of crytsal violet on proteins. Colloids Surf A. 2001;186:173–7.

    Article  Google Scholar 

  28. Bonnekoh B, Wevers A, Jugert F, Merk H, Mahrle G. Colorimetric growth assy for epidermal cell cultures by their crystal violet binding capacity. Arch Dermatol Res. 1989;281:487–790.

    Article  CAS  PubMed  Google Scholar 

  29. Saji M, Taguchi S, Uchiyama K, Osono E, Hayama N, Ohkuni H. Efficacy of gentian violet in the eradication of methicillin-resistant staphylococcus aureus from skin lesions. J Hosp Infect. 1995;31:225–8.

    Article  CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

We gratefully acknowledge financial support from the Landesstiftung Baden-Württemberg (contract number 4-4332.62-HSG/34). We are also highly thankful to Dr. Barke for providing us with pig skin.

Author information

Authors and Affiliations

  1. HSG-IMIT, Wilhelm-Schickard-Str. 10, 78052, Villingen-Schwenningen, Germany

    Michael Vosseler, Michael Jugl & Roland Zengerle

  2. Laboratory for MEMS Applications Department of Microsystems Engineering—IMTEK, University of Freiburg, Georges-Koehler Allee 106, 79110, Freiburg, Germany

    Roland Zengerle

Authors
  1. Michael Vosseler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Jugl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland Zengerle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Vosseler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vosseler, M., Jugl, M. & Zengerle, R. A Smart Interface for Reliable Intradermal Injection and Infusion of High and Low Viscosity Solutions. Pharm Res 28, 647–661 (2011). https://doi.org/10.1007/s11095-010-0319-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-010-0319-z

KEY WORDS

Search

Navigation