Skip to main content
SpringerLink
Log in

The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems

  • Research Article
  • Theme: Printing and Additive Manufacturing
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

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

Similar content being viewed by others

References

  1. Zhao L, Ren T, Wang DD. Clinical pharmacology considerations in biologics development. Acta Pharmacol Sin. 2012;33:1339–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Irvine DJ, Su X, Kwong B. Routes of delivery for biological drug products. Pharm Sci Encycl [Internet]. John Wiley & Sons, Inc.; 2010 [cited 2015 Aug 11]. Available from:http://onlinelibrary.wiley.com/doi/10.1002/9780470571224.pse521/abstract.

  3. Blackstone EA, Joseph PF. The economics of biosimilars. Am Health Drug Benefits. 2013;6:469–78.

    PubMed  PubMed Central  Google Scholar 

  4. Jin J, Zhu L, Chen M, Xu H, Wang H, Feng X, et al. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection. Patient Prefer Adherence. 2015;9:923–42.

    PubMed  PubMed Central  Google Scholar 

  5. Petrak F, Herpertz S, Stridde E, Pfützner A. Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections or inhaled insulin. Diabetes Technol Ther. 2013;15:703–11.

    CAS  PubMed  Google Scholar 

  6. Vangeli E, Bakhshi S, Baker A, Fisher A, Bucknor D, Mrowietz U, et al. A systematic review of factors associated with non-adherence to treatment for immune-mediated inflammatory diseases. Adv Ther. 2015;32:983–1028.

    PubMed  PubMed Central  Google Scholar 

  7. Yavuz DG, Ozcan S, Deyneli O. Adherence to insulin treatment in insulin-naïve type 2 diabetic patients initiated on different insulin regimens. Patient Prefer Adherence. 2015;9:1225–31.

    PubMed  PubMed Central  Google Scholar 

  8. Montenegro-Nicolini M, Morales JO. Overview and future potential of buccal mucoadhesive films as drug delivery systems for biologics. AAPS PharmSciTech [Internet]. 2016 [cited 2016 Apr 19]; Available from: http://link.springer.com/10.1208/s12249-016-0525-z

  9. Nanci A. Ten Cate’s oral histology: development, structure and function, Elsevier Health Sciences; 2008.

  10. Morales JO, Huang S, Williams RO, McConville JT. Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery. Colloids Surf B Biointerfaces. 2014;122:38–45.

    CAS  PubMed  Google Scholar 

  11. Harde H, Agrawal AK, Jain S. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration. Drug Deliv Transl Res. 2015;5:498–510.

    CAS  PubMed  Google Scholar 

  12. Chen G, Bunt C, Wen J. Mucoadhesive polymers-based film as a carrier system for sublingual delivery of glutathione. J Pharm Pharmacol. 2015;67:26–34.

    CAS  PubMed  Google Scholar 

  13. Parodi B, Russo E, Baldassari S, Zuccari G, Pastorino S, Yan M, et al. Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy. Drug Dev Ind Pharm. 2017;43:917–24.

    CAS  PubMed  Google Scholar 

  14. Bala R, Pawar P, Khanna S, Arora S. Orally dissolving strips: a new approach to oral drug delivery system. Int J Pharm Investig. 2013;3:67–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control Release. 2009;139:94–107.

    CAS  PubMed  Google Scholar 

  16. Silva MM, Calado R, Marto J, Bettencourt A, Almeida AJ, Gonçalves LMD. Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration. Mar Drugs. 2017;15.

    PubMed Central  Google Scholar 

  17. Montenegro-Nicolini M, Miranda V, Morales JO. Inkjet printing of proteins: an experimental approach. AAPS J [Internet]. 2016 [cited 2016 Oct 15]; Available from: http://link.springer.com/10.1208/s12248-016-9997-8

  18. Buanz ABM, Belaunde CC, Soutari N, Tuleu C, Gul MO, Gaisford S. Ink-jet printing versus solvent casting to prepare oral films: effect on mechanical properties and physical stability. Int J Pharm. 2015;494:611–8.

    CAS  PubMed  Google Scholar 

  19. Siemann U. Solvent cast technology—a versatile tool for thin film production. Scatt Methods Prop Polym Mater [Internet]. Springer; 2005 [cited 2015 Oct 21]. p. 1–14. Available from: http://link.springer.com/chapter/10.1007/b107336

  20. Netchacovitch L, Thiry J, De Bleye C, Dumont E, Dispas A, Hubert C, et al. A simple calibration approach based on film-casting for confocal Raman microscopy to support the development of a hot-melt extrusion process. Talanta. 2016;154:392–9.

    CAS  PubMed  Google Scholar 

  21. Tang Y, Liang G, Chen J, Yu S, Li Z, Rao L, et al. Highly reflective nanofiber films based on electrospinning and their application on color uniformity and luminous efficacy improvement of white light-emitting diodes. Opt Express. 2017;25:20598–611.

    CAS  PubMed  Google Scholar 

  22. Schruben DL, Gonzalez P. Dispersity improvement in solvent casting particle/polymer composite. Polym Eng Sci. 2000;40:139–42.

    CAS  Google Scholar 

  23. Huang Z-M, Zhang Y-Z, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol. 2003;63:2223–53.

    CAS  Google Scholar 

  24. Preis M, Woertz C, Kleinebudde P, Breitkreutz J. Oromucosal film preparations: classification and characterization methods. Expert Opin Drug Deliv. 2013;10:1303–17.

    CAS  PubMed  Google Scholar 

  25. Dahiya M, Saha S, Shahiwala AF. A review on mouth dissolving films. Curr Drug Deliv. 2009;6:469–76.

    CAS  PubMed  Google Scholar 

  26. Shepherd R, Reader S, Falshaw A. Chitosan functional properties. Glycoconj J. 1997;14:535–42.

    CAS  PubMed  Google Scholar 

  27. Yuan G, Chen X, Li D. Chitosan films and coatings containing essential oils: the antioxidant and antimicrobial activity, and application in food systems. Food Res Int. 2016;89:117–28.

    CAS  PubMed  Google Scholar 

  28. Nicolazzo JA, Reed BL, Finnin BC. Buccal penetration enhancers—how do they really work? J Control Release. 2005;105:1–15.

    CAS  PubMed  Google Scholar 

  29. Wu C-S. A comparison of the structure, thermal properties, and biodegradability of polycaprolactone/chitosan and acrylic acid grafted polycaprolactone/chitosan. Polymer. 2005;46:147–55.

    CAS  Google Scholar 

  30. Woodruff MA, Hutmacher DW. The return of a forgotten polymer—polycaprolactone in the 21st century. Prog Polym Sci. 2010;35:1217–56.

    CAS  Google Scholar 

  31. Zhou Q, Zhang H, Zhou Y, Yu Z, Yuan H, Feng B, et al. Alkali-mediated miscibility of gelatin/polycaprolactone for electrospinning homogeneous composite nanofibers for tissue scaffolding. Macromol Biosci. 2017;17

  32. Genina N, Janßen EM, Breitenbach A, Breitkreutz J, Sandler N. Evaluation of different substrates for inkjet printing of rasagiline mesylate. Eur J Pharm Biopharm. 2013;85:1075–83.

    CAS  PubMed  Google Scholar 

  33. Tang ZG, Black RA, Curran JM, Hunt JA, Rhodes NP, Williams DF. Surface properties and biocompatibility of solvent-cast poly[ε-caprolactone] films. Biomaterials. 2004;25:4741–8.

    CAS  PubMed  Google Scholar 

  34. Zhang Y, Ouyang H, Lim CT, Ramakrishna S, Huang Z-M. Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J Biomed Mater Res B Appl Biomater. 2005;72:156–65.

    PubMed  Google Scholar 

  35. Qin X, Wu D. Effect of different solvents on poly(caprolactone) (PCL) electrospun nonwoven membranes. J Therm Anal Calorim. 2012;107:1007–13.

    CAS  Google Scholar 

  36. Beachley V, Wen X. Effect of electrospinning parameters on the nanofiber diameter and length. Mater Sci Eng C Mater Biol Appl. 2009;29:663–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Katsogiannis KAG, Vladisavljević GT, Georgiadou S. Porous electrospun polycaprolactone (PCL) fibres by phase separation. Eur Polym J. 2015;69:284–95.

    CAS  Google Scholar 

  38. Morales JO, Ross AC, McConville JT. Protein-coated nanoparticles embedded in films as delivery platforms. J Pharm Pharmacol. 2013;65:827–38.

    CAS  PubMed  Google Scholar 

  39. D20 Committee. Test method for tensile properties of thin plastic sheeting D882–02 [Internet]. ASTM International; 2012. Available from: http://www.astm.org/doiLink.cgi?D882.

  40. Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm. 2011;77:187–99.

    CAS  PubMed  Google Scholar 

  41. Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M, et al. Development of mucoadhesive patches for buccal administration of ibuprofen. J Control Release. 2004;99:73–82.

    CAS  PubMed  Google Scholar 

  42. Rotta J, Minatti E, Barreto PLM. Determination of structural and mechanical properties, diffractometry, and thermal analysis of chitosan and hydroxypropylmethylcellulose (HPMC) films plasticized with sorbitol. Food Sci Technol Camp. 2011;31:450–5.

    Google Scholar 

  43. Ford JL. Thermal analysis of hydroxypropylmethylcellulose and methylcellulose: powders, gels and matrix tablets. Int J Pharm. 1999;179:209–28.

    CAS  PubMed  Google Scholar 

  44. Sakurai K, Maegawa T, Takahashi T. Glass transition temperature of chitosan and miscibility of chitosan/poly(N-vinyl pyrrolidone) blends. Polymer. 2000;41:7051–6.

    CAS  Google Scholar 

  45. Speranza V, Sorrentino A, De Santis F, Pantani R. Characterization of the polycaprolactone melt crystallization: complementary optical microscopy, DSC, and AFM studies [Internet]. Sci. World J. 2014 [cited 2018 Mar 4]. Available from: https://www.hindawi.com/journals/tswj/2014/720157/

  46. Darbasi M, Askari G, Kiani H, Khodaiyan F. Development of chitosan based extended-release antioxidant films by control of fabrication variables. Int J Biol Macromol. 2017;104:303–10.

    CAS  PubMed  Google Scholar 

  47. Rabek CL, Stelle RV, Dziubla TD, Puleo DA. The effect of plasticizers on the erosion and mechanical properties of polymeric films. J Biomater Appl [Internet]. 2014;28. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766411/.

  48. Joshi S, Petereit H-U. Film coatings for taste masking and moisture protection. Int J Pharm. 2013;457:395–406.

    CAS  PubMed  Google Scholar 

  49. Tian H, Liu D, Yao Y, Ma S, Zhang X, Xiang A. Effect of sorbitol plasticizer on the structure and properties of melt processed polyvinyl alcohol films. J Food Sci. 2017;82:2926–32.

    CAS  PubMed  Google Scholar 

  50. Gupta RK. Fundamentals of polymers. McGraw-Hill; 1998.

  51. Meier MM, Kanis LA, Soldi V. Characterization and drug-permeation profiles of microporous and dense cellulose acetate membranes: influence of plasticizer and pore forming agent. Int J Pharm. 2004;278:99–110.

    CAS  PubMed  Google Scholar 

  52. Prateepchanachai S, Thakhiew W, Devahastin S, Soponronnarit S. Mechanical properties improvement of chitosan films via the use of plasticizer, charge modifying agent and film solution homogenization. Carbohydr Polym. 2017;174:253–61.

    CAS  PubMed  Google Scholar 

  53. Prabu D, Majdalawieh AF, Abu-Yousef IA, Inbasekaran K, Balasubramaniam T, Nallaperumal N, et al. Preparation and characterization of gatifloxacin-loaded sodium alginate hydrogel membranes supplemented with hydroxypropyl methylcellulose and hydroxypropyl cellulose polymers for wound dressing. Int J Pharm Investig. 2016;6:86–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Leach MK, Feng Z-Q, Tuck SJ, Corey JM. Electrospinning fundamentals: optimizing solution and apparatus parameters. J Vis Exp JoVE [Internet]. 2011; Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182658/.

  55. Sarac AS. Nanofibers of conjugated polymers. CRC Press; 2016.

  56. Croisier F, Duwez A-S, Jérôme C, Léonard AF, van der Werf KO, Dijkstra PJ, et al. Mechanical testing of electrospun PCL fibers. Acta Biomater. 2012;8:218–24.

    CAS  PubMed  Google Scholar 

  57. Al-Dhubiab BE, Al-Dhubiab BE. In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem. Braz Oral Res [Internet]. 2016 [cited 2017 Oct 21];30. Available from: http://www.scielo.br/scielo.php?script=sci_abstract&pid=S1806-83242016000100316&lng=en&nrm=iso&tlng=en.

  58. Agarwal S, Murthy RSR. Effect of different polymer concentration on drug release rate and physicochemical properties of Mucoadhesive gastroretentive tablets. Indian J Pharm Sci. 2015;77:705–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Mati-Baouche N, Elchinger P-H, de Baynast H, Pierre G, Delattre C, Michaud P. Chitosan as an adhesive. Eur Polym J. 2014;60:198–212.

    CAS  Google Scholar 

  60. Lo H-Y, Kuo H-T, Huang Y-Y. Application of polycaprolactone as an anti-adhesion biomaterial film. Artif Organs. 2010;34:648–53.

    PubMed  Google Scholar 

  61. Shi Q, Wong S-C, Ye W, Hou J, Zhao J, Yin J. Mechanism of adhesion between polymer fibers at nanoscale contacts. Langmuir. 2012;28:4663–71.

    CAS  PubMed  Google Scholar 

  62. Mortazavian E, Dorkoosh FA, Rafiee-Tehrani M. Design, characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin. Drug Dev Ind Pharm. 2014;40:691–8.

    CAS  PubMed  Google Scholar 

  63. Vuddanda PR, Alomari M, Dodoo CC, Trenfield SJ, Velaga S, Basit AW, et al. Personalisation of warfarin therapy using thermal ink-jet printing. Eur J Pharm Sci. 2018;117:80–7.

    CAS  PubMed  Google Scholar 

  64. Janßen EM, Schliephacke R, Breitenbach A, Breitkreutz J. Drug-printing by flexographic printing technology—a new manufacturing process for orodispersible films. Int J Pharm. 2013;441:818–25.

    PubMed  Google Scholar 

  65. Pinheiro MJ, Freitas S, Miranda EA, de Alcântara Pessôa Filho P. Solubility of lysozyme in aqueous solution containing ethanol or acetone: unexpected dependence on the initial protein concentration. Fluid Phase Equilib. 2016;429:9–13.

    CAS  Google Scholar 

  66. Meléndez PA, Kane KM, Ashvar CS, Albrecht M, Smith PA. Thermal inkjet application in the preparation of oral dosage forms: dispensing of prednisolone solutions and polymorphic characterization by solid-state spectroscopic techniques. J Pharm Sci. 2008;97:2619–36.

    PubMed  Google Scholar 

  67. Wickström H, Palo M, Rijckaert K, Kolakovic R, Nyman JO, Määttänen A, et al. Improvement of dissolution rate of indomethacin by inkjet printing. Eur J Pharm Sci. 2015;75:91–100.

    PubMed  Google Scholar 

  68. Choi M, Park HH, Choi D, Han U, Park TH, Lee H, et al. Multilayer nanofilms via inkjet printing for stabilizing growth factor and designing desired cell developments. Adv Healthc Mater. 2017;6:n/a-n/a.

  69. HP. Product specifications: HP 61XL black ink cartridge [Internet]. [cited 2018 Mar 13]. Available from: http://store.hp.com/us/en/pdp/hp-61xl-high-yield-black-original-ink-cartridge-p-ch563wn-140--1.

  70. HP. Product specifications: HP 61XL tri-color ink cartridge [Internet]. [cited 2018 Mar 13]. Available from: http://store.hp.com/us/en/pdp/hp-61xl-high-yield-tri-color-original-ink-cartridge-p-ch564wn-140--1.

  71. Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharm J. 2016;24:537–46.

    PubMed  Google Scholar 

  72. Planchette C, Pichler H, Wimmer-Teubenbacher M, Gruber M, Gruber-Woelfler H, Mohr S, et al. Printing medicines as orodispersible dosage forms: Effect of substrate on the printed micro-structure. Int J Pharm [Internet]. [cited 2016 Feb 25]; Available from: http://www.sciencedirect.com/science/article/pii/S0378517315303227

Download references

Funding

M. Montenegro-Nicolini acknowledges the funding support from CONICYT 21150995. J.O. Morales thanks the financial support from FONDECYT 1181689 and FONDAP 15130011. Andrónico Neira-Carrillo thanks the financial support from FONDECYT 1171520.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, 4to piso, Oficina # 09, Independencia, 8380494, Santiago, Chile

    Miguel Montenegro-Nicolini, Miguel O. Jara & Javier O. Morales

  2. Instituto de Salud Pública de Chile, 7780050, Santiago, Chile

    Miguel Montenegro-Nicolini & Patricio E. Reyes

  3. Pharmaceutical Biomaterial Research Group, Department of Health Sciences, Luleå University of Technology, 97187, Luleå, Sweden

    Parameswara R. Vuddanda, Sitaram Velaga & Javier O. Morales

  4. Advanced Center for Chronic Diseases (ACCDiS), 8380494, Santiago, Chile

    Andrónico Neira-Carrillo, Nicole Butto & Javier O. Morales

  5. Faculty of Veterinary and Animal Sciences, University of Chile, Santiago, Chile

    Andrónico Neira-Carrillo & Nicole Butto

Authors
  1. Miguel Montenegro-Nicolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricio E. Reyes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel O. Jara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Parameswara R. Vuddanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrónico Neira-Carrillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicole Butto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sitaram Velaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Javier O. Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Javier O. Morales.

Ethics declarations

Conflict of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Guest Editors: Niklas Sandler and Jukka Rantanen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Montenegro-Nicolini, M., Reyes, P.E., Jara, M.O. et al. The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems. AAPS PharmSciTech 19, 3376–3387 (2018). https://doi.org/10.1208/s12249-018-1105-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-018-1105-1

KEY WORDS

Search

Navigation