Advertisement

Drug Delivery and Translational Research

, Volume 8, Issue 1, pp 32–42 | Cite as

Jet dispensing of multi-layered films for the co-delivery of three antihypertensive agents

  • Nicolaos Scoutaris
  • Maria Malamatari
  • Adrien Letellier
  • Dennis DouroumisEmail author
Original Article
  • 210 Downloads

Abstract

Three-layer thin films comprising of two polymers as substrate (ethyl cellulose and, copovidone K28) and three antihypertensive agents (hydrochlorothiazide, amiloride HCl, and carvedilol) were printed using jet dispensing technology. Two film formulations with different ethyl cellulose to copovidone K28 ratio (i.e., 90/10 and 50/50 w/w) were prepared using a three-course dispensing. The films were characterized regarding surface morphology, solid-state properties, polymer-drug interactions, drug distribution in each layer, and in vitro drug release. All the components of the films were found to be in the amorphous state apart from hydrochlorothiazide which retained its crystallinity. FT-IR spectroscopy revealed hydrogen bond interactions between carvedilol and copovidone K28. Combinations of ethyl cellulose and copovidone K28 provide suitable polymeric film substrates with the ability to modify drug release. Particularly, decreased ethyl cellulose to copovidone K28 weight ratio was found to suppress the crystallization of hydrochlorothiazide and to increase the release rate of the dispensed drugs. Jet dispensing was found to be a rapid technology for the preparation of multi-layered films that can be used as personalized formulations for the delivery of combinations of drugs.

Keywords

Jet dispensing Films Combination therapy Antihypertensive drugs 

Notes

Acknowledgements

The authors are grateful to Ms. Devyani Amin (University of Greenwich) for her help with the development of the HPLC method.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kalra S, Kalra B, Agrawal N. Combination therapy in hypertension: an update. Diabetol Metab Syndr. 2010;2:44.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Haller H. Effective management of hypertension with dihydropyridine calcium channel blocker-based combination therapy in patients at high cardiovascular risk. Int J Clin Pract. 2008;62:781–90.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lafeber M, Grobbee DE, Bots ML, Thom S, Webster R, Rodgers A, et al. The evening versus morning polypill utilization study: the TEMPUS rationale and design. Eur J Prev Cardiol. 2014;21:425–33.CrossRefPubMedGoogle Scholar
  4. 4.
    Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of tablets containing multiple drugs with defined release profiles. Int J Pharm. 2015;494:643–50.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Scoutaris N, Snowden M, Douroumis D. Taste masked thin films printed by jet dispensing. Int J Pharm. 2015;494:619–22.CrossRefPubMedGoogle Scholar
  7. 7.
    Scoutaris N, Nion A, Hurt A, Douroumis D. Jet dispensing as a high throughput method for rapid screening and manufacturing of cocrystals. CrystEngComm. 2016;18:5079–82.CrossRefGoogle Scholar
  8. 8.
    Joint Formulatory Commitee. British National Formulary (BNF) 72 ed. London: BMJ Group and Pharmaceutical Press; 2016.Google Scholar
  9. 9.
    Frishman WH, Henderson LS, Lukas MA. Controlled-release carvedilol in the management of systemic hypertension and myocardial dysfunction. Vasc Health Risk Manag. 2008;4:1387–400.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Langdon CG, Baxter GA, Young PH. A multicenter comparison of carvedilol with hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension. J Cardiovasc Pharmacol. 1991;18:S51–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Taddei S. Combination therapy in hypertension: what are the best options according to clinical pharmacology principles and controlled clinical trial evidence? Am J Cardiovasc Drugs. 2015;15:185–94.CrossRefPubMedGoogle Scholar
  12. 12.
    Chantaburanan T, Teeranachaideekul V, Chantasart D, Jintapattanakit A, Junyaprasert VB. Effect of binary solid lipid matrix of wax and triglyceride on lipid crystallinity, drug-lipid interaction and drug release of ibuprofen-loaded solid lipid nanoparticles (SLN) for dermal delivery. J Colloid Interface Sci. 2017;504:247–56.CrossRefPubMedGoogle Scholar
  13. 13.
    Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm. 2011;77:187–99.CrossRefPubMedGoogle Scholar
  14. 14.
    Alomari M, Mohamed FH, Basit AW, Gaisford S. Personalised dosing: printing a dose of one’s own medicine. Int J Pharm. 2015;494:568–77.CrossRefPubMedGoogle Scholar
  15. 15.
    Wening K, Breitkreutz J. Oral drug delivery in personalized medicine: unmet needs and novel approaches. Int J Pharm. 2011;404:1–9.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    Stephenson GA, Forbes RA, Reutzel-Edens SM. Characterization of the solid state: quantitative issues. Adv Drug Deliv Rev. 2001;48:67–90.CrossRefPubMedGoogle Scholar
  18. 18.
    Pires MAS, Dos Santos RAS, Sinisterra RD. Pharmaceutical composition of hydrochlorothiazide:β-cyclodextrin: preparation by three different methods, physico-chemical characterization and in vivo diuretic activity evaluation. Molecules. 2011;16:4482–99.CrossRefPubMedGoogle Scholar
  19. 19.
    Senta-Loys Z, Bourgeois S, Valour JP, Briançon S, Fessi H. Orodispersible films based on amorphous solid dispersions of tetrabenazine. Int J Pharm. 2017;518:242–52.CrossRefPubMedGoogle Scholar
  20. 20.
    Korhonen K, Smolander E, Korhonen O, Ketolainen J, Laitinen R. Effect of storage on the physical stability of thin polymethacrylate-perphenazine films. Eur J Pharm Sci. 2017;104:293–301.CrossRefPubMedGoogle Scholar
  21. 21.
    Mistry P, Mohapatra S, Gopinath T, Vogt FG, Suryanarayanan R. Role of the strength of drug-polymer interactions on the molecular mobility and crystallization inhibition in ketoconazole solid dispersions. Mol Pharm. 2015;12:3339–50.CrossRefPubMedGoogle Scholar
  22. 22.
    Scoutaris N, Alexander MR, Gellert PR, Roberts CJ. Inkjet printing as a novel medicine formulation technique. J Control Release. 2011;156:179–85.CrossRefPubMedGoogle Scholar
  23. 23.
    Tajber L, Corrigan OI, Healy AM. Physicochemical evaluation of PVP-thiazide diuretic interactions in co-spray-dried composites - analysis of glass transition composition relationships. Eur J Pharm Sci. 2005;24:553–63.CrossRefPubMedGoogle Scholar
  24. 24.
    Adsmond DA, Grant DJW. Hydrogen bonding in sulfonamides. J Pharm Sci. 2001;90:2058–77.CrossRefPubMedGoogle Scholar
  25. 25.
    Marques MPM, Oliveira PJ, Moreno AJM, Batista De Carvalho LAE. Study of carvedilol by combined Raman spectroscopy and ab initio MO calculations. J Raman Spectrosc. 2002;33:778–83.CrossRefGoogle Scholar
  26. 26.
    Zhang X, Wang Y, Wang J, Wang Y, Li S. Effect of pore former on the properties of casted film prepared from blends of Eudragit NE 30 D and Eudragit L 30 D-55. Chem Pharm Bull (Tokyo). 2007;55:1261–3.CrossRefGoogle Scholar
  27. 27.
    Yang M, Xie S, Li Q, Wang Y, Chang X, Shan L, et al. Effects of polyvinylpyrrolidone both as a binder and pore-former on the release of sparingly water-soluble topiramate from ethylcellulose coated pellets. Int J Pharm. 2014;465:187–96.CrossRefPubMedGoogle Scholar
  28. 28.
    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.CrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2017

Authors and Affiliations

  • Nicolaos Scoutaris
    • 1
  • Maria Malamatari
    • 1
  • Adrien Letellier
    • 1
    • 2
  • Dennis Douroumis
    • 1
    Email author
  1. 1.Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and ScienceUniversity of GreenwichKentUK
  2. 2.University of RouenMont-Saint-AignanFrance

Personalised recommendations