SpringerLink
Log in

Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium

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

Abstract

The aim of this study was to investigate the influence of the production method and the polymeric carrier on the ability to generate and maintain the supersaturation of a poorly soluble drug in biorelevant medium. The amorphous solid dispersion of sulfamethoxazole, an antibacterial drug, was produced using two different polymers by spray-drying or hot melt extrusion methods. When Eudragit EPO was used, supersaturation was maintained up to 24 h for both techniques at all drug-polymer proportions. However, when Soluplus was employed in hot melt extrusion, a smaller amount of drug was dissolved when compared to the amorphous drug. The proportion of 3:7 drug-Eudragit EPO (w/w) produced by spray-drying presented a higher amount of drug dissolved in supersaturation studies and it was able to maintain the physical stability under different storage conditions throughout the 90-day evaluation. Supersaturation generation and system stability were found to be related to more effective chemical interaction between the polymer and the drug provided by the production method, as revealed by the 1D ROESY NMR experiment. Investigation of drug-polymer interaction is critical in supersaturating drug delivery systems to avoid crystallization of the drug and to predict the effectiveness of the system. Chemical compounds studied in this article: Sulfamethoxazole (PubChem CID: 4539) and Methacrylate copolymer — Eudragit EPO (PubChem CID: 65358)

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

Access this article

Log in via an institution

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 includes VAT (Spain)

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

Abbreviations

API:

Active pharmaceutical ingredients

ASD:

Amorphous solid dispersion

BCS:

Biopharmaceutical Classification System

FaSSIF:

Fasted State Simulated Intestinal Fluid

SDDS:

Supersaturating drug delivery systems

SLM:

Sulfamethoxazole

Soluplus:

Polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer

References

  1. Brouwers J, Brewster ME, Augustijns P. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J Pharm Sci. 2009;98(8):2549–72.

    Article  CAS  Google Scholar 

  2. Raina SA, Zhang GGZ, Alonzo DE, Wu J, Zhu D, Catron ND, et al. Enhancements and limits in drug membrane transport using supersaturated solutions of poorly water soluble drugs. J Pharm Sci. 2014;103(9):2736–48.

    Article  CAS  Google Scholar 

  3. Taylor LS, Zhang GGZ. Physical chemistry of supersaturated solutions and implications for oral absorption. Adv Drug Deliv Rev. 2016;101:122–42.

    Article  CAS  Google Scholar 

  4. Gilley AD, Arca HC, Nichols BLB, Mosquera-Giraldo LI, Taylor LS, Edgar KJ, et al. Novel cellulose-based amorphous solid dispersions enhance quercetin solution concentrations in vitro. Carbohydr Polym. 2017;157:86–93.

    Article  CAS  Google Scholar 

  5. Zhou D, He S, Cong Y, **e Z, Chen X, **g X, et al. A polymer-(multifunctional single-drug) conjugate for combination therapy. J Mater Chem B. 2015;3(24):4913–21.

    Article  CAS  Google Scholar 

  6. Santos A, Sinn Aw M, Bariana M, Kumeria T, Wang Y, Losic D. Drug-releasing implants: current progress, challenges and perspectives. J Mater Chem B. 2014;2:6157–82.

  7. Adebisi AO, Kaialy W, Hussain T, Al-Hamidi H, Nokhodchi A, Conway BR, et al. Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions. Colloids Surfaces B Biointerfaces [Internet]. 2016 Oct 1 [cited 2018 Sep 3];146:841–51. Available from: https://www.sciencedirect.com/science/article/pii/S0927776516305343

  8. Harmon P, Galipeau K, Xu W, Brown C, Wuelfing WP. Mechanism of dissolution-induced nanoparticle formation from a Copovidone-based amorphous solid dispersion. Mol Pharm. 2016;13(5):1467–81.

    Article  CAS  Google Scholar 

  9. Genina N, Hadi B, Löbmann K. Hot melt extrusion as solvent-free technique for a continuous manufacturing of drug-loaded mesoporous silica. J Pharm Sci. 2018;107(1):149–55.

    Article  CAS  Google Scholar 

  10. Paudel A, Worku ZA, Meeus J, Guns S, Van Den Mooter G. Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int J Pharm. 2013;453(1):253–84.

    Article  CAS  Google Scholar 

  11. Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm. 2004;58(2):265–78.

    Article  Google Scholar 

  12. Eliopoulos GM, Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis. 2001;32(11):1608–14.

    Article  Google Scholar 

  13. Alonzo DE, Zhang GGZ, Zhou D, Gao Y, Taylor LS. Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm Res. 2010;27(4):608–18.

    Article  CAS  Google Scholar 

  14. PA Masters, TA O'Bryan, J Zurlo, DQ Miller, N Joshi Trimethoprim-sulfamethoxazole revisited. Arch Intern Med 2003;163(4):402–410. Available from: https://doi.org/10.1001/archinte.163.4.402

  15. Tian Y, Jones DS, Andrews GP. An investigation into the role of polymeric carriers on crystal growth within amorphous solid dispersion systems. Mol Pharm. 2015;12(4):1180–92.

    Article  CAS  Google Scholar 

  16. Caron V, Hu Y, Tajber L, Erxleben A, Corrigan OI, McArdle P, et al. Amorphous solid dispersions of sulfonamide/soluplus® and sulfonamide/PVP prepared by ball milling. AAPS PharmSciTech. 2013;14(1):464–74.

    Article  CAS  Google Scholar 

  17. Pharmacopieial Convention U. S. USP [Internet]. Estándares de Referencia 2008. Available from: http://www.usp.org/es/estandares-de-referencia/hojas-de-datos-tecnicos

  18. ICH guidelines. Q2(R1): Validation of analytical procedures: text and methodology. Int Conf Harmon. 2005;1994(November 1996):17.

  19. Niu J, Zhang L, Li Y, Zhao J, Lv S, **ao K. Effects of environmental factors on sulfamethoxazole photodegradation under simulated sunlight irradiation: kinetics and mechanism. J Environ Sci (China). 2013;25(6):1098–106.

    Article  CAS  Google Scholar 

  20. Wang P, Zhang D, Zhang H, Li H, Ghosh S, Pan B. Impact of concentration and species of sulfamethoxazole and ofloxacin on their adsorption kinetics on sediments. Chemosphere. 2017;175:123–9.

    Article  CAS  Google Scholar 

  21. Hardung H, Djuric D, Ali S. Combining HME & solubilization: Soluplus® - the solid solution. Drug Deliv Technol. 2010;10(3):20–7.

    CAS  Google Scholar 

  22. Khachane P, Date AA, Nagarsenker MS. Eudragit EPO nanoparticles: application in improving therapeutic efficacy and reducing ulcerogenicity of meloxicam on oral administration. J Biomed Nanotechnol. 2011;7(4):590–7.

    Article  CAS  Google Scholar 

  23. Barbosa JAC, Abdelsadig MSE, Conway BR, Merchant HA. Using zeta potential to study the ionisation behaviour of polymers employed in modified-release dosage forms and estimating their pKa. Int J Pharm X. 2019;1:100024. Available from: https://doi.org/10.1016/j.ijpx.2019.100024.

  24. **e T, Gao W, Taylor LS. Impact of Eudragit EPO and hydroxypropyl methylcellulose on drug release rate, supersaturation, precipitation outcome and redissolution rate of indomethacin amorphous solid dispersions. Int J Pharm. 2017;531:313–23.

    Article  CAS  Google Scholar 

  25. Thiry J, Broze G, Pestieau A, Tatton AS, Baumans F, Damblon C, et al. Investigation of a suitable in vitro dissolution test for itraconazole-based solid dispersions. Eur J Pharm Sci. 2016;85:94–105.

    Article  CAS  Google Scholar 

  26. **a D, Yu H, Tao J, Zeng J, Zhu Q, Zhu C, et al. Supersaturated polymeric micelles for oral cyclosporine A delivery: the role of Soluplus–sodium dodecyl sulfate complex. Colloids Surfaces B Biointerfaces [Internet]. 2016 May 1 [cited 2018 Sep 3];141:301–10. Available from: https://www.sciencedirect.com/science/article/pii/S0927776516300479

  27. Hughey JR, Keen JM, Miller DA, Kolter K, Langley N, McGinity JW. The use of inorganic salts to improve the dissolution characteristics of tablets containing Soluplus??-based solid dispersions. Eur J Pharm Sci 2013;48(4–5):758–766. Available from: https://doi.org/10.1016/j.ejps.2013.01.004

Download references

Acknowledgments

The authors would like to thank Dr. Adailton J. Bortoluzzi for technical support during XRPD analyses, Laboratório Central de Microscopia Eletrônica (LCME) for SEM measurements and Post-graduation Program in Chemistry of Universidade Federal de Santa Catarina for the facilities.

Funding

This study was supported by the Coordination for Enhancement of Higher Education Personnel (CAPES) — financial code 001.

Author information

Authors and Affiliations

  1. Grupo de Estudos em Materiais Poliméricos (POLIMAT), Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Cassiana Mendes, Rafael G. Andrzejewski & Alexandre L. Parize

  2. Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Juliana M. O. Pinto & Marcos A. S. Silva

  3. Centro de RMN, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Leice M. R. de Novais & Andersson Barison

Authors
  1. Cassiana Mendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rafael G. Andrzejewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliana M. O. Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leice M. R. de Novais
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andersson Barison
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcos A. S. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alexandre L. Parize
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cassiana Mendes.

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.

Electronic Supplementary Material

ESM 1

(DOCX 2099 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mendes, C., Andrzejewski, R.G., Pinto, J.M.O. et al. Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium. AAPS PharmSciTech 21, 189 (2020). https://doi.org/10.1208/s12249-020-01737-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-020-01737-6

KEY WORDS

Search

Navigation