Skip to main content
SpringerLink
Log in

Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) I: Use of Poloxamer 188 as Both Solidifying and Emulsifying Agent for Lipids

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

ABSTRACT

Purpose

To develop solid self-emulsifying drug delivery systems (SEDDS) for lipids using poloxamer 188 as both solidifying and emulsifying agents.

Methods

Mixtures of various lipids with poloxamer 188 and PEG 8000 were prepared at ~75°C. The molten mixtures, with and without dissolved drugs (fenofibrate and probucol), were then cooled to room temperature. When solids formed, they were characterized by powder XRD, DSC, microscopy using cross-polarization and confocal fluorescence techniques, dispersion test in water and particle size analysis of dispersions.

Results

When mixed with poloxamer 188 or PEG 8000, lipids consisting of monoesters of fatty acids with glycerol or propylene glycol formed solid systems, but not di- and tri-esters, which showed phase separation. Added to water, the solid systems containing poloxamer 188 started to disperse in water forming oil globules of 200–600 nm. No emulsification of lipids was observed from solids containing PEG 8000, indicating that the surfactant property of poloxamer 188 was responsible for emulsification. Powder XRD, DSC and microscopic examination revealed that poloxamer 188 and PEG 8000 maintained their crystallinity in solid systems, while the lipids were interspersed in between crystalline regions. The drug remained solubilized in the lipid phase.

Conclusions

A novel solid SEDDS is developed where the drug can be solubilized in liquid lipids and then the lipidic solution can be converted to solid mass by dispersing into the microstructure of poloxamer 188.

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
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

REFERENCES

  1. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26.

    Article  PubMed  CAS  Google Scholar 

  2. Hörter D, Dressman J. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001;46(1–3):75–87.

    Article  PubMed  Google Scholar 

  3. Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Deliv Rev. 1997;25(1):103–28.

    Article  CAS  Google Scholar 

  4. Porter CJH, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev. 2008;60(6):673–91.

    Article  PubMed  CAS  Google Scholar 

  5. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs: drug delivery and drug efficacy. Biomed Pharmacother. 2004;58(3):173–82.

    Article  PubMed  Google Scholar 

  6. Strickly RG. Currently marketed oral lipid-based dosage forms: drug products and excipients. In: Hauss D, editor. Lipid-based formulations for oral drug delivery: enhancing bioavailability of poorly water-soluble drugs. New York: Informa Healthcare; 2007. p. 1–31.

    Google Scholar 

  7. Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm. 1994;106(1):15–23.

    Article  CAS  Google Scholar 

  8. Bachynsky MO, Shah NH, Patel CI, Malick AW. Factors affecting the efficiency of a self-emulsifying oral delivery system. Drug Dev Ind Pharm. 1997;23(8):809–16.

    Article  CAS  Google Scholar 

  9. Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev. 1997;25(1):47–58.

    Article  CAS  Google Scholar 

  10. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci. 2000;11:S93–8.

    Article  PubMed  CAS  Google Scholar 

  11. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29(3–4):278–87.

    Article  PubMed  CAS  Google Scholar 

  12. Hauss DJ. Oral lipid-based formulations. Adv Drug Deliv Rev. 2007;59(7):667–76.

    Article  PubMed  CAS  Google Scholar 

  13. Jannin V, Musakhanian J, Marchaud D. Approaches for the development of solid and semi-solid lipid-based formulations. Adv Drug Deliv Rev. 2008;60(6):734–46.

    Article  PubMed  CAS  Google Scholar 

  14. Vasanthavada M, Serajuddin ATM. Lipid-based self-emulsifying solid dispersions. In: Hauss D, editor. Lipid-based formulations for oral drug delivery: enhancing bioavailability of poorly water soluble drugs. New York: Informa Healthcare; 2007. p. 149–84.

    Google Scholar 

  15. Savolainen M, Khoo C, Glad H, Dahlqvist C, Juppo AM. Evaluation of controlled-release polar lipid microparticles. Int J Pharm. 2002;244(1–2):151–61.

    Article  PubMed  CAS  Google Scholar 

  16. Desai D, Kothari S, Chen W, Wang J, Huang M, Sharma L. Fatty acid and water–soluble polymer–based controlled release drug delivery system. J Pharm Sci. 2011;100(5):1900–12.

    Article  PubMed  CAS  Google Scholar 

  17. Aoshima H, Miyagisnima A, Nozawa Y, Sadzuka Y, Sonobe T. Glycerin fatty acid esters as a new lubricant of tablets. Int J Pharm. 2005;293(1–2):25–34.

    Article  PubMed  CAS  Google Scholar 

  18. Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today. 2008;13(13–14):606–12.

    Article  PubMed  CAS  Google Scholar 

  19. Cole ET, Cadé D, Benameur H. Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration. Adv Drug Deliv Rev. 2008;60(6):747–56.

    Article  PubMed  CAS  Google Scholar 

  20. Ito Y, Kusawake T, Ishida M, Tawa R, Shibata N, Takada K. Oral solid gentamicin preparation using emulsifier and adsorbent. J Control Release. 2005;105(1–2):23–31.

    Article  PubMed  CAS  Google Scholar 

  21. Patil P, Paradkar A. Porous polystyrene beads as carriers for self-emulsifying system containing loratadine. AAPS PharmSciTech. 2006;7(1):E1–7.

    Article  Google Scholar 

  22. Abdalla A, Klein S, Mäder K. A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: characterization, dissolution, in vitro digestion and incorporation into solid pellets. Eur J Pharm Sci. 2008;35(5):457–64.

    Article  PubMed  CAS  Google Scholar 

  23. Agarwal V, Siddiqui A, Ali H, Nazzal S. Dissolution and powder flow characterization of solid self-emulsified drug delivery system (SEDDS). Int J Pharm. 2009;366(1–2):44–52.

    Article  PubMed  CAS  Google Scholar 

  24. Wang Z, Sun J, Wang Y, Liu X, Liu Y, Fu Q, Meng P, He Z. Solid self-emulsifying nitrendipine pellets: preparation and in vitro/in vivo evaluation. Int J Pharm. 2010;383(1–2):1–6.

    Article  PubMed  CAS  Google Scholar 

  25. Tan A, Davey AK, Prestidge CA. Silica-Lipid Hybrid (SLH) versus non-lipid formulations for optimising the dose-dependent oral absorption of celecoxib. Pharm Res. 2011;28(9):2273–87.

    Article  PubMed  CAS  Google Scholar 

  26. Hansen T, Holm P, Schultz K. Process characteristics and compaction of spray-dried emulsions containing a drug dissolved in lipid. Int J Pharm. 2004;287(1–2):55–66.

    Article  PubMed  CAS  Google Scholar 

  27. Dollo G, Le Corre P, Guérin A, Chevanne F, Burgot JL, Leverge R. Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs. Eur J Pharm Sci. 2003;19(4):273–80.

    Article  PubMed  CAS  Google Scholar 

  28. Yi T, Wan J, Xu H, Yang X. A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs. Eur J Pharm Biopharm. 2008;70(2):439–44.

    Article  PubMed  CAS  Google Scholar 

  29. Nazzal S, Nutan M, Palamakula A, Shah R, Zaghloul AA, Khan MA. Optimization of a self-nanoemulsified tablet dosage form of Ubiquinone using response surface methodology: effect of formulation ingredients. Int J Pharm. 2002;240(1–2):103–14.

    Article  PubMed  CAS  Google Scholar 

  30. Nazzal S, Khan MA. Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters. Int J Pharm. 2006;315(1–2):110–21.

    Article  PubMed  CAS  Google Scholar 

  31. Nazzal S, Zaghloul AA, Khan MA. Effect of Extragranular Microcrystalline Cellulose on compaction, surface roughness, and in vitro dissolution of a self-nanoemulsified solid dosage forms of ubiquinone. Pharm Tech. 2002;26:86–98.

    CAS  Google Scholar 

  32. Li P, Hynes SR, Haefele TF, Pudipeddi M, Royce AE, Serajuddin ATM. Development of clinical dosage forms for a poorly water–soluble drug II: formulation and characterization of a novel solid microemulsion preconcentrate system for oral delivery of a poorly water–soluble drug. J Pharm Sci. 2009;98(5):1750–64.

    Article  PubMed  CAS  Google Scholar 

  33. Margulis-Goshen K, Kamyshny A, Magdassi S. Applications of surfactants in pharmaceutical dosage forms. In: Zoller U, editor. Handbook of detergents, part E: applications. Boca Raton: CRC; 2008. p. 455–66.

    Google Scholar 

  34. Vippagunta SR, Maul KA, Tallavajhala S, Grant DJW. Solid-state characterization of nifedipine solid dispersions. Int J Pharm. 2002;236(1–2):111–23.

    Article  PubMed  CAS  Google Scholar 

  35. Chen Y, Zhang GGZ, Neilly J, Marsh K, Mawhinney D, Sanzgiri YD. Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68. Int J Pharm. 2004;286(1–2):69–80.

    Article  PubMed  CAS  Google Scholar 

  36. Brüsewitz C, Schendler A, Funke A, Wagner T, Lipp R. Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of active compounds. Int J Pharm. 2007;329(1–2):173–81.

    Article  PubMed  Google Scholar 

  37. Fernandez-Tarrio M, Yañez F, Immesoete K, Alvarez-Lorenzo C, Concheiro A. Pluronic and Tetronic copolymers with polyglycolyzed oils as self-emulsifying drug delivery systems. AAPS PharmSciTech. 2008;9(2):471–9.

    Article  PubMed  CAS  Google Scholar 

  38. Rowe RC, Sheskey PJ, Weller PJ. Handbook of pharmaceutical excipients. London: Pharmaceutical; 2006. p. 447–50.

    Google Scholar 

  39. Cannon JB, Long MA. Emulsions, microemulsions, and lipid-based drug delivery systems for drug solubilization and delivery-Part II: Oral applications. In: Liu R, editor. Water-insoluble drug formulation. Boca Raton: CRC; 2008. p. 227–53.

    Chapter  Google Scholar 

  40. Prajapati HN, Dalrymple DM, Serajuddin ATM. A comparative evaluation of mono, di and triglyceride of medium chain fatty acids by lipid/surfactant/water phase diagram, solubility determination and dispersion testing for application in pharmaceutical dosage form development. Pharm Res. 2012;29(1):285–305.

    Article  PubMed  CAS  Google Scholar 

  41. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.

    Article  PubMed  CAS  Google Scholar 

  42. Morris KR, Knipp GT, Serajuddin ATM. Structural properties of polyethylene glycol—polysorbate 80 mixture, a solid dispersion vehicle. J Pharm Sci. 1992;81(12):1185–8.

    Article  PubMed  CAS  Google Scholar 

  43. Law TK, Whateley TL, Florence AT. Some chemically modified poloxamer hydrogels: preparation, morphology and swelling properties. Int J Pharm. 1984;21(3):277–87.

    Article  CAS  Google Scholar 

  44. Ginés JM, Arias MJ, Moyano JR, Sánchez-Soto PJ. Thermal investigation of crystallization of polyethylene glycols in solid dispersions containing oxazepam. Int J Pharm. 1996;143(2):247–53.

    Article  Google Scholar 

  45. Hosier IL, Bassett DC, Vaughan AS. Spherulitic growth and cellulation in dilute blends of monodisperse long n-alkanes. Macromolecules. 2000;33:8781–90.

    Article  CAS  Google Scholar 

  46. Gránásy L, Pusztai T, Tegze G, Warren JA, Douglas JF. Growth and form of spherulites. Phys Rev E. 2005;72(1):011605.

    Article  Google Scholar 

  47. Billmeyer Jr FW, Ceil PH, van der Weg KR. Growth and observation of spherulites in polyethylene: a high polymer demonstration. J Chem Educ. 1960;37(9):460–1.

    Article  CAS  Google Scholar 

  48. Mohsin K, Long MA, Pouton CW. Design of lipid–based formulations for oral administration of poorly water–soluble drugs: precipitation of drug after dispersion of formulations in aqueous solution. J Pharm Sci. 2009;98(10):3582–95.

    Article  PubMed  CAS  Google Scholar 

  49. Yagi N, Terashima Y, Kenmotsu H, Sekikawa H, Takada M. Dissolution behavior of probucol from solid dispersion systems of probucol-polyvinylpyrrolidone. Chem Pharm Bull. 1996;44(1):241–4.

    Article  CAS  Google Scholar 

  50. Nielsen FS, Gibault E, Ljusberg-Wahren H, Arleth L, Pedersen JS, Müllertz A. Characterization of prototype self–nanoemulsifying formulations of lipophilic compounds. J Pharm Sci. 2007;96(4):876–92.

    Article  PubMed  CAS  Google Scholar 

  51. Rane SS, Anderson BD. What determines drug solubility in lipid vehicles: is it predictable? Adv Drug Deliv Rev. 2008;60(6):638–56.

    Article  PubMed  CAS  Google Scholar 

  52. Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001;212(2):233–46.

    Article  PubMed  CAS  Google Scholar 

  53. Craig D. Polyethyelene glycols and drug release. Drug Dev Ind Pharm. 1990;16(17):2501–26.

    Article  CAS  Google Scholar 

  54. Craig DQM. A review of thermal methods used for the analysis of the crystal form, solution thermodynamics and glass transition behaviour of polyethylene glycols. Thermochim Acta. 1995;248:189–203.

    Article  CAS  Google Scholar 

  55. Mahlin D, Ridell A, Frenning G, Engström S. Solid-state characterization of PEG 4000/monoolein mixtures. Macromolecules. 2004;37(7):2665–7.

    Article  CAS  Google Scholar 

  56. Tejwani RW, Joshi HN, Varia SA, Serajuddin A. Study of phase behavior of poly (ethylene glycol)–polysorbate 80 and poly (ethylene glycol)–polysorbate 80–water mixtures. J Pharm Sci. 2000;89(7):946–50.

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS & DISCLOSURES

The authors thank ABITEC Corp., 501 W 1st Avenue, Columbus, OH 43215, USA for a research grant that partially supported this project. They also thank Mr. Louis E. Bryan from the department of Biological Sciences, St. John’s University, for his assistance in confocal fluorescence microscopic analysis of samples.

Author information

Authors and Affiliations

  1. College of Pharmacy and Allied Health Professions Department of Pharmaceutical Sciences, St. John’s University, 8000 Utopia Parkway, Queens, New York, 11439, USA

    Ankita V. Shah & Abu T. M. Serajuddin

Authors
  1. Ankita V. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abu T. M. Serajuddin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abu T. M. Serajuddin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, A.V., Serajuddin, A.T.M. Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) I: Use of Poloxamer 188 as Both Solidifying and Emulsifying Agent for Lipids. Pharm Res 29, 2817–2832 (2012). https://doi.org/10.1007/s11095-012-0704-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-012-0704-x

KEY WORDS

Search

Navigation