AAPS PharmSciTech

, Volume 19, Issue 7, pp 3040–3047 | Cite as

Effect of the Interaction Between an Ionic Surfactant and Polymer on the Dissolution of a Poorly Soluble Drug

  • Vaishnavi ParikhEmail author
  • Suhas G. Gumaste
  • Shivaji Phadke
Research Article


Surfactants are commonly incorporated in conventional and enabled formulations to enhance the rate and extent of dissolution of drugs exhibiting poor aqueous solubility. Generally the interactions between the drug and excipients are systematically evaluated, however, limited attention is paid towards understanding the effect of interaction between functional excipients and its impact on the performance of the product. In the current study, the effect of potential interaction between a nonionic polymer binder, povidone, and anionic surfactant docusate sodium on the rate and extent of dissolution of a drug exhibiting poor aqueous solubility was evaluated by varying the proportions of the binder and the surfactant in the formulation. Potential complexation or aggregation between the excipients was investigated by fluorescence spectroscopy and zeta potential measurements of the aqueous solutions of docusate sodium, povidone, and sodium lauryl sulfate (SLS). The rate and extent of drug release was found to decrease with an increase in the proportion of docusate sodium and povidone in the formulations. Difference in magnitude of surface charge (zeta potential) of docusate sodium in presence of povidone indicated potential surfactant-polymer aggregation during dissolution which was corroborated by CAC/CMC values derived from fluorescence spectroscopic measurements. The decrease in the rate of drug release was attributed to an increase in the viscosity of the microenvironment of dissolving particles due to the interaction of docusate sodium and povidone in the aqueous media during dissolution. These findings highlight the importance of systematic evaluation of the interaction of ionic surfactants with the polymeric components within the formulation to ensure the appropriate selection of the type of surfactant as well as its proportion in the formulation.


polyvinylpyrrolidone docusate sodium sodium lauryl sulfate dissolution anionic surfactants polymer-surfactant aggregation 


SLS Sodium lauryl sulfate

PVP Polyvinylpyrrolidone

DS Docusate sodium


  1. 1.
    Reddy RK, Khalil SA, Wafik Gouda M. Effect of dioctyl sodium sulfosuccinate and poloxamer 188 on dissolution and intestinal absorption of sulfadiazine and sulfisoxazole in rats. J Pharm Sci. 1976;65(1):115–8.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sjökvist E, Nyström C, Aldén M, Caram-Lelham N. Physicochemical aspects of drug release. XIV. The effects of some ionic and non-ionic surfactants on properties of a sparingly soluble drug in solid dispersions. Int J Pharm. 1992;79(1):123–33.CrossRefGoogle Scholar
  3. 3.
    Brown S, Rowley G, Pearson JT. Surface treatment of the hydrophobic drug danazol to improve drug dissolution. Int J Pharm. 1998;165(2):227–37.CrossRefGoogle Scholar
  4. 4.
    Serajuddin ATM, Sheen PC, Augustine MA. Improved dissolution of a poorly water-soluble drug from solid dispersions in polyethylene glycol: Polysorbate 80 mixtures. J Pharm Sci. 1990;79(5):463–4.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wong SM, Kellaway IW, Murdan S. Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles. Int J Pharm. 2006;317(1):61–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Per F, Sissel S. Dissolution kinetics of drugs in human gastric juice—the role of surface tension. J Pharm Sci. 1968;57(8):1322–6.CrossRefGoogle Scholar
  7. 7.
    Milo G, Stuart F. Mechanisms of surfactant effects on drug absorption. J Pharm Sci. 1970;59(5):579–89.CrossRefGoogle Scholar
  8. 8.
    Patel HJ, Parikh VP. An overview of osmotic drug delivery system: an update review. Int J Bioassays. 2017;6(7):5426–36.CrossRefGoogle Scholar
  9. 9.
    Shah SH, Patel VR, Shah VR, Vaghani ZH, Thakkar AY. Nanotechnology: a review on revolution in cancer treatment. Pharm Rev. 2008;6(6).Google Scholar
  10. 10.
    Gumaste SG, Gupta SS, Serajuddin ATM. Investigation of polymer-surfactant and polymer-drug-surfactant miscibility for solid dispersion. AAPS J. 2016;18(5):1131–43.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Shah VP, Konecny JJ, Everett RL, McCullough B, Noorizadeh AC, Skelly JP. In vitro dissolution profile of water-insoluble drug dosage forms in the presence of surfactants. Pharm Res. 1989;6(7):612–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ofner CM, Zhang YE, Jobeck VC, Bowman BJ. Crosslinking studies in gelatin capsules treated with formaldehyde and in capsules exposed to elevated temperature and humidity. J Pharm Sci. 2001;90(1):79–88.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Digenis GA, Gold TB, Shah VP. Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance. J Pharm Sci. 1994;83(7):915–21.CrossRefGoogle Scholar
  14. 14.
    Cole ET. Liquid-filled and sealed hard gelatin capsule technologies. In: Rathbone MJ, Hadgraft J, editors. Modified-release drug delivery technology. Boca Raton: CRC Press; 2002. p. 177–90.CrossRefGoogle Scholar
  15. 15.
    Nilsson S. Interactions between water-soluble cellulose derivatives and surfactants. 1. The HPMC/SDS/water system. Macromolecules. 1995;28(23):7837–44.CrossRefGoogle Scholar
  16. 16.
    Azum N, Asiri AM, Rub MA, Al-Youbi AO, Khan A. Thermodynamic aspects of polymer–surfactant interactions: Gemini (16-5-16)-PVP-water system. Arab J Chem. 2016;9:S1660–S4.CrossRefGoogle Scholar
  17. 17.
    Holmberg C, Nilsson S, Sundelöf L-O. Thermodynamic properties of surfactant/polymer/water systems with respect to clustering adsorption and intermolecular interaction as a function of temperature and polymer concentration. Langmuir. 1997;13(6):1392–9.CrossRefGoogle Scholar
  18. 18.
    Kumar N, Tyagi R. Analysis of the interactions of polyvinylpyrrolidone with conventional anionic and dimeric anionic surfactant. J Dispers Sci Technol. 2015;36(11):1601–6.CrossRefGoogle Scholar
  19. 19.
    Qi S, Roser S, Edler KJ, Pigliacelli C, Rogerson M, Weuts I, et al. Insights into the role of polymer-surfactant complexes in drug solubilisation/stabilisation during drug release from solid dispersions. Pharm Res. 2013;30(1):290–302.CrossRefGoogle Scholar
  20. 20.
    de Martins RM, Silva CA, Becker C, Samios D, Bica CID, Christoff M. Studies on anionic surfactant structure in the aggregation with (hydroxypropyl)cellulose. Polimeros. 2002;12:109–14.Google Scholar
  21. 21.
    Goddard ED. Polymer—surfactant interaction part I. Uncharged water-soluble polymers and charged surfactants. Colloids Surf. 1986;19(2):255–300.CrossRefGoogle Scholar
  22. 22.
    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(2):119–29.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    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(3):962–74.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Goddard ED, Turro NJ, Kuo PL, Ananthapadmanabhan KP. Fluorescence probes for critical micelle concentration determination. Langmuir. 1985;1(3):352–5.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Shah VR, Gupta PK. Structural stability of recombinant human growth hormone (r-hgh) as a function of polymer surface properties. Pharm Res. 2018;35(5):98.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sawant RR, Sawant RM, Torchilin VP. Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: improved drug solubilization and enhanced in vitro cytotoxicity. Eur J Pharm Biopharm. 2008;70(1):51–7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    La SB, Okano T, Kataoka K. Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated polyfethylene oxide)-poly(β-benzyl l-aspartate) block copolymer micelles. J Pharm Sci. 1996;85(1):85–90.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    White B, Banerjee S, O'Brien S, Turro NJ, Herman IP. Zeta-potential measurements of surfactant-wrapped individual single-walled carbon nanotubes. J Phys Chem C. 2007;111(37):13684–90.CrossRefGoogle Scholar
  29. 29.
    US FDA. Inactive ingredient search for approved drug products 2018 [cited 2018 5/1/2018]. Available from:
  30. 30.
    Chambliss WG, Cleary RW, Fischer R, Jones AB, Skierkowski P, Nicholes W, et al. Effect of docusate sodium on drug release from a controlled-release dosage form. J Pharm Sci. 1981;70(11):1248–51.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Aguiar J, Carpena P, Molina-Bolı́var JA, Carnero Ruiz C. On the determination of the critical micelle concentration by the pyrene 1:3 ratio method. J Colloid Interface Sci. 2003;258(1):116–22.CrossRefGoogle Scholar
  32. 32.
    Bhattacharjee S. DLS and zeta potential – what they are and what they are not? J Control Release. 2016;235:337–51.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Vaishnavi Parikh
    • 1
    Email author
  • Suhas G. Gumaste
    • 1
  • Shivaji Phadke
    • 1
  1. 1.Product DevelopmentGenus Lifesciences Inc.AllentownUSA

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