Impact of Surfactants on Polymer Maintained Nifedipine Supersaturation in Aqueous Solution

Abstract

Purpose

To study the impact of different surfactants on the supersaturation of nifedipine stabilized with HPMC and PVP-VA.

Methods

Different kinds of surfactants, including one cationic surfactant, two anionic surfactants, and three nonionic surfactants, were used to evaluate their impacts on the supersaturation of nifedipine stabilized with HPMC and PVP-VA. Polymer-surfactant interaction was studied by nuclear magnetic resonance (NMR) and fluorescent method. Solubility of nifedipine in solutions containing different amounts of polymers and surfactants was measured. Drug-polymer affinity was evaluated by measuring the percentage of polymer coprecipitated together with the drug from supersaturated solutions.

Results

Different polymer-surfactant combinations had different impacts on the supersaturation of nifedipine. Some combinations, such as PVP-VA/SLS and PVP-VA/NaTC under higher surfactant concentrations, showed improved drug supersaturation, due to increased drug solubility or polymer-surfactant synergy; while other combinations, such as HPMC/SLS and HPMC/Tween 20 under lower surfactant concentrations, showed reduced drug supersaturation, which could result from competitive surfactant-polymer or drug-surfactant interaction that disrupted pre-existent drug-polymer interaction.

Conclusions

The ultimate impacts of various surfactants on polymer stabilized nifedipine supersaturation could be attributed to the interplay between different factors, including solubility enhancement of the drug, drug-polymer-surfactant interactions, and polymer-surfactant synergy.

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

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

Abbreviations

AUC:

Area under the curve

CAC:

Critical aggregation concentration CMC

Critical micelle concentration DMSO

Dimethylsulfoxide

DTAB:

Dodecyl trimethyl ammonium bromide

ELSD:

Evaporative light scattering detector

GI:

Gastrointestinal

HPLC:

High performance liquid chromatography

HPMC:

Hydroxypropyl methylcellulose

NaTC:

Sodium taurocholate

NMR:

Nuclear magnetic resonance

PBS:

Phosphatic buffer solution

PCP:

Polymer coprecipitation percentage

PVP-VA:

Polyvinylpyrrolidone-co-vinyl-acetate

PXRD:

Powder x-ray diffraction

SDDS:

Supersaturating drug delivery systems

SLS:

Sodium lauryl sulfate

SP:

Supersaturation parameter

TPGS:

D-α-Tocopherol polyethylene glycol succinate

UV:

Ultraviolet

References

  1. 1.

    Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. Journal of Pharmacological & Toxicological Methods. 2000;44:235–49.

    CAS  Article  Google Scholar 

  2. 2.

    Lipinski CA. Poor aqueous solubility -an industry wide problem in ADME screening. American Pharmaceutical Review. 2002;5:82–5.

    Google Scholar 

  3. 3.

    C.A. Lipinski. Physicochemical properties and the discovery of orally active drugs: technical and people issues. Molecular Informatics: Confronting Complexity, May 13th - 16th 2002, Bozen, Italy (2003).

  4. 4.

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

    CAS  Article  Google Scholar 

  5. 5.

    Liu C, Chen Z, Chen Y, Lu J, Li Y, Wang S, et al. Improving oral bioavailability of Sorafenib by optimizing the "spring" and "parachute" based on molecular interaction mechanisms. Mol Pharm. 2015;13:599.

    Article  Google Scholar 

  6. 6.

    Guzmán HR, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P, Gardner CR, et al. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J Pharm Sci. 2007;96:2686–702.

    Article  Google Scholar 

  7. 7.

    Xuand S, Dai WG. Drug precipitation inhibitors in supersaturable formulations. Int J Pharm. 2013;453:36–43.

    Article  Google Scholar 

  8. 8.

    Y. Chen, C. Liu, C. Zhen, C. Su, M. Hageman, M. Hussain, R. Haskell, K. Stefanski, and Q. Feng. Drug–polymer–water interaction and its implication for the dissolution performance of amorphous solid dispersions. Molecular Pharmaceutics. 12:(2015).

    CAS  Article  Google Scholar 

  9. 9.

    Chen Y, Wang S, Shan W, Liu C, Su C, Hageman M, et al. Sodium lauryl sulfate competitively interacts with HPMC-AS and consequently reduces oral bioavailability of Posaconazole/HPMC-AS amorphous solid dispersion. Mol Pharm. 2016;13:2787–95.

    CAS  Article  Google Scholar 

  10. 10.

    Lu Y, Tang N, Lian R, Qi J, Wu W. Understanding the relationship between wettability and dissolution of solid dispersion. Int J Pharm. 2014;465:25–31.

    CAS  Article  Google Scholar 

  11. 11.

    M. Rahman, S. Ahmad, J. Tarabokija, N. Parker, and E. Bilgili. Spray-dried amorphous solid dispersions of griseofulvin in HPC/Soluplus/SDS: elucidating the multifaceted impact of sds as a minor component. Pharmaceutics. 12:(2020).

    Article  Google Scholar 

  12. 12.

    Ghebremeskel AN, Vemavarapu C, Lodaya M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int J Pharm. 2007;328:119–29.

    CAS  Article  Google Scholar 

  13. 13.

    Solanki NG, Lam K, Tahsin M, Gumaste SG, Shah AV, Serajuddin ATM. Effects of surfactants on Itraconazole-HPMCAS solid dispersion prepared by hot-melt extrusion I: miscibility and drug release. J Pharm Sci. 2019;108:1453–65.

    CAS  Article  Google Scholar 

  14. 14.

    Heng PWS, Wan LSC, Ang TSH. Role of surfactant on drug release from tablets. Drug Development Communications. 1990;16:951–62.

    CAS  Google Scholar 

  15. 15.

    Chen J, Mosquera-Giraldo LI, Ormes JD, Higgins JD, Taylor LS. Bile salts as crystallization inhibitors of supersaturated solutions of poorly water-soluble compounds. Cryst Growth Des. 2015;15:2593–7.

    CAS  Article  Google Scholar 

  16. 16.

    Lu J, Ormes JD, Lowinger M, Mann AKP, Xu W, Litster JD, et al. Maintaining Supersaturation of active pharmaceutical ingredient solutions with biologically relevant bile salts. Cryst Growth Des. 2017;17:2782–91.

    CAS  Article  Google Scholar 

  17. 17.

    D. Feng, T. Peng, Z. Huang, V. Singh, Y. Shi, T. Wen, M. Lu, G. Quan, X. Pan, and C. Wu. Polymer(−)Surfactant system based amorphous solid dispersion: precipitation inhibition and bioavailability enhancement of itraconazole. Pharmaceutics. 10:(2018).

    Article  Google Scholar 

  18. 18.

    Meng F, Ferreira R, Zhang F. Effect of surfactant level on properties of celecoxib amorphous solid dispersions. Journal of Drug Delivery Science and Technology. 2019;49:301–7.

    CAS  Article  Google Scholar 

  19. 19.

    D. Xia, H. Yu, J. Tao, J. Zeng, Q. Zhu, C. Zhu, and Y. Gan. Supersaturated polymeric micelles for oral cyclosporine A delivery: The role of Soluplus-sodium dodecyl sulfate complex. Colloids and surfaces B, Biointerfaces. 141:301–310 (2016).

    CAS  Article  Google Scholar 

  20. 20.

    Mah PT, Peltonen L, Novakovic D, Rades T, Strachan CJ, Laaksonen T. The effect of surfactants on the dissolution behavior of amorphous formulations. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2016;103:13–22.

    CAS  Article  Google Scholar 

  21. 21.

    Baghel S, Cathcart H, O'Reilly NJ. Investigation into the solid-state properties and dissolution profile of spray-dried ternary amorphous solid dispersions: a rational step toward the design and development of a multicomponent amorphous system. Mol Pharm. 2018;15:3796–812.

    CAS  Article  Google Scholar 

  22. 22.

    Chen Y, Wang S, Wang S, Liu C, Su C, Hageman M, et al. Initial drug dissolution from amorphous solid dispersions controlled by polymer dissolution and drug-polymer interaction. Pharm Res. 2016;33:2445–58.

    Article  Google Scholar 

  23. 23.

    Pateland SG, Bummer PM. Thermodynamics of aggregate formation between a non-ionic polymer and ionic surfactants: an isothermal titration calorimetric study. Int J Pharm. 2017;516:131–43.

    Article  Google Scholar 

  24. 24.

    Goddard E, Turro N, Kuo P, Ananthapadmanabhan K. Fluorescence probes for critical micelle concentration determination. Langmuir. 1985;1:352–5.

    CAS  Article  Google Scholar 

  25. 25.

    von Rechenberg M, Blake BK, Ho YS, Zhen Y, Chepanoske CL, Richardson BE, et al. Ampicillin/penicillin-binding protein interactions as a model drug-target system to optimize affinity pull-down and mass spectrometric strategies for target and pathway identification. Proteomics. 2005;5:1764–73.

    Article  Google Scholar 

  26. 26.

    A. Brymora, V.A. Valova, and P.J. Robinson. Protein-protein interactions identified by pull-down experiments and mass spectrometry. Current protocols in cell biology. 22:17.15. 11–17.15. 51 (2004).

    Article  Google Scholar 

  27. 27.

    Wang S, Liu C, Chen Y, Zhu A, Qian F. Aggregation of Hydroxypropyl methylcellulose AcetateSuccinate under its dissolving pH and the impact on drug Supersaturation. Mol Pharm. 2018;15:4643–53.

    CAS  Article  Google Scholar 

  28. 28.

    Pui Y, Chen Y, Chen H, Wang S, Liu C, Tonnis W, et al. Maintaining Supersaturation of Nimodipine by PVP with or without the presence of sodium lauryl sulfate and sodium Taurocholate. Mol Pharm. 2018;15:2754–63.

    CAS  Article  Google Scholar 

  29. 29.

    Kashchievand D, Van Rosmalen G. Nucleation in solutions revisited. Crystal Research and Technology: Journal of Experimental and Industrial Crystallography. 2003;38:555–74.

    Article  Google Scholar 

  30. 30.

    Lu J, Ormes JD, Lowinger M, Mann AKP, Xu W, Patel S, et al. Impact of bile salts on solution crystal growth rate and residual Supersaturation of an active pharmaceutical ingredient. Cryst Growth Des. 2017;17:3528–37.

    CAS  Article  Google Scholar 

  31. 31.

    Chen J, Ormes JD, Higgins JD, Taylor LS. Impact of surfactants on the crystallization of aqueous suspensions of celecoxib amorphous solid dispersion spray dried particles. Mol Pharm. 2015;12:533–41.

    CAS  Article  Google Scholar 

  32. 32.

    Ilevbare GA, Liu H, Edgar KJ, Taylor LS. Effect of binary additive combinations on solution crystal growth of the poorly water-soluble drug. Ritonavir Crystal Growth & Design. 2012;12:6050–60.

    CAS  Article  Google Scholar 

  33. 33.

    Mosquera-Giraldo LI, Trasi NS, Taylor LS. Impact of surfactants on the crystal growth of amorphous celecoxib. Int J Pharm. 2014;461:251–7.

    CAS  Article  Google Scholar 

  34. 34.

    Deshpande TM, Shi H, Pietryka J, Hoag SW, Medek A. Investigation of polymer/surfactant interactions and their impact on Itraconazole solubility and precipitation kinetics for developing spray-dried amorphous solid dispersions. Mol Pharm. 2018;15:962–74.

    CAS  Article  Google Scholar 

  35. 35.

    Sunand DD, Lee PI. Haste makes waste: the interplay between dissolution and precipitation of supersaturating formulations. AAPS J. 2015;17:1317–26.

    Article  Google Scholar 

  36. 36.

    Schverand GC, Lee PI. Combined effects of supersaturation rates and doses on the kinetic- solubility profiles of amorphous solid dispersions based on water-insoluble poly (2- hydroxyethyl methacrylate) hydrogels. Mol Pharm. 2018;15:2017–26.

    Article  Google Scholar 

  37. 37.

    Chen Y, Pui Y, Chen H, Wang S, Serno P, Tonnis W, et al. Polymer-mediated drug supersaturation controlled by drug–polymer interactions persisting in an aqueous environment. Mol Pharm. 2018;16:205–13.

    Article  Google Scholar 

  38. 38.

    H. Konno, T. Handa, De, and L. Taylor Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine European Journal of Pharmaceutics & Biopharmaceutics 70:493–499 (2008).

  39. 39.

    Baghel S, Cathcart H, O'Reilly NJ. Understanding the generation and maintenance of supersaturation during the dissolution of amorphous solid dispersions using modulated DSC and (1)H NMR. Int J Pharm. 2018;536:414–25.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This research is supported by China National Nature Science Foundation (Project Number 81573355), and by Janssen Pharmaceuticals, Inc., a pharmaceutical company of Johnson & Johnson.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Alan (Donghua) Zhu or Feng Qian.

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 383 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Liu, C., Chen, H. et al. Impact of Surfactants on Polymer Maintained Nifedipine Supersaturation in Aqueous Solution. Pharm Res 37, 113 (2020). https://doi.org/10.1007/s11095-020-02837-5

Download citation

Keywords

  • HPMC
  • nifedipine
  • PVP-VA
  • supersaturation
  • surfactants