Journal of Pharmaceutical Investigation

, Volume 49, Issue 1, pp 27–36 | Cite as

Development of ethosomal vesicular carrier for topical application of griseofulvin: effect of ethanol concentration

  • Chukwuemeka C. MbahEmail author
  • Philip F. Builders
  • Chukwuma O. Agubata
  • Anthony A. Attama
Original Article


Vesicular carriers (VCs) offer enhanced and sustained delivery of drugs. The aim of this study was to explore the effects of ethanol concentration in VCs on topical delivery of a poorly water-soluble drug, using griseofulvin as prototype. VCs containing varying quantities of ethanol were prepared by solvent evaporation using Phospholipon® 90H (P90H) and characterized for entrapment efficiency (EE), morphology, size and size distribution, stability, viscosity and skin retention. Permeation profiles were assessed using rat skin and Franz diffusion cell and withdrawn samples analyzed spectrophotometrically. Spherical vesicles of average size of 137.70 ± 51.62 nm and polydipersity index of 0.555 were produced. Vesicle sizes decreased with increase in ethanol concentration. EE of 68.0 ± 5.6% was obtained for the optimized formulation. Differential scanning calorimetry indicated reversible perturbation of the skin layers as the mechanism of permeation. Permeation generally increased with increase in ethanol concentration. Ethosomal nanovesicular carriers encapsulating griseofulvin were formulated, which showed potentials for sustained and enhanced delivery through rat skin in direct proportion with ethanol concentration.


Vesicular carriers Ethosomes Nanotechnology Characterization of vesicular carriers Enhanced delivery Griseofulvin 



We thank NIPRD, Abuja and Sheda Science and Technology Complex (SHESTCO), Abuja, Nigeria for some of the facilities utilized in this research work.

Compliance with ethical standards

Declaration of conflict of interest

The authors declare no conflict of interest in this research work. No sponsorship was received in carrying out this work and while preparing the article.

Research involving human and animal participants

No human subjects were used for this study. All the institutional and national guidelines for the care and use of laboratory animals were followed in accordance with the ethical procedures of NIPRD, Abuja, Nigeria (Number: 05:3:06), in line with the National Institute of Health guidelines, as revised, 1985, for handling of laboratory animals.


  1. Agubata CO, Nzekwe IT, Attama AA, Müller-Goymann CC, Onunkwo GC (2015) Formulation, characterization and anti-malarial activity of homolipid-based artemether microparticles. Int J Pharm 478:202–222CrossRefGoogle Scholar
  2. Attama AA, Reichl S, Müller-Goymann CC (2008) Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int J Pharm 355:307–313CrossRefGoogle Scholar
  3. Attama AA, Reichl S, Müller-Goymann CC (2009) Sustained release and permeation of timolol from surface-modified solid-lipid nanoparticles through bioengineered human cornea. Curr Eye Res 34:698–705CrossRefGoogle Scholar
  4. Aulton ME (1999) Pharmaceutics: the science of dosage form design. Ist edn. Churchill Livingstone, EdinburghGoogle Scholar
  5. Barry BW (2001) Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 14(2):101–114CrossRefGoogle Scholar
  6. Bendas ER, Tadros MI (2007) Enhanced transdermal delivery of salbutamol sulfate via ethosomes. AAPS Pharm Sci Tech 8(4):E107CrossRefGoogle Scholar
  7. Brookfield Engineering Labs Inc (2014) More solutions to sticky problems: a guide to getting MORE from your Brookfield Viscometers 1–50. Accessed 28 Feb 2014
  8. Carter SJ (1987) Jellies formulation: sodium alginate. In: Cooper and gun’s dispensing for pharmaceutical students, 12th edn. Churchill Livingstone, Edinburgh, pp 214–218Google Scholar
  9. Chernysheva YV, Babak VG, Kildeeva NR, Boury F, Benoit JP, Ubrich N, Maincent P (2003) Effect of the type of hydrophobic polymers on the size of nanoparticles obtained by emulsion-solvent evaporation. Mendeleev Commun 13:65–68CrossRefGoogle Scholar
  10. Chu KA, Yalkowsky SH (2009) An interesting relationship between drug absorption and melting point. Int J Pharm 373:24–40CrossRefGoogle Scholar
  11. Cilurzo F, Albert E, Minghetti P, Gennari CGM, Casiraghi A, Montanari L (2010) Effect of drug chirality on the skin permeability of ibuprofen. Int J Pharm 386:71–76CrossRefGoogle Scholar
  12. El Khyat A, Mavon A, Leduc M, Agache P, Humbert P (1996) Skin critical surface tension. Skin Res Technol 2(2):91–96CrossRefGoogle Scholar
  13. El Maghraby GM, Barry BW, Williams AC (2008) Liposomes and skin: from drug delivery to model membranes. Eur J Pharm Sci 34:203–222CrossRefGoogle Scholar
  14. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM (2007) Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 332:1–16CrossRefGoogle Scholar
  15. Ghafourian T, Samaras EG, Brooks JD, Riviere JE (2010) Validated models for predicting skin penetration from different vehicles. Eur J Pharm Sci 41:612–616CrossRefGoogle Scholar
  16. Goodman M, Barry BW (1989) Action of penetration enhancers on human stratum corneum as assessed by differential scanning calorimetry. In: Bronaugh RL, Maibach HI (eds) Percutaneous absorption, 2nd edn. Marcel Dekker, New York, pp 567–595Google Scholar
  17. GuhaSarkar S, Banerjee R (2010) Intravesical drug delivery: challenges, current status, opportunities and novel strategies. J Control Release 148:147–159CrossRefGoogle Scholar
  18. Jain S, Tiwary AK, Sapra B, Jain NK (2007) Formulation and evaluation of ethosomes for transdermal delivery of lamivudine. AAPS Pharm Sci Tech 8(4):Article111. CrossRefGoogle Scholar
  19. Karavelidis V, Giliopoulos D, Karavas E, Bikiaris DN (2010) Nanoencapsulation of a water soluble drug in biocompatible polyesters: effects of polyesters melting point and glass transition temperature on drug release behavior. Eur J Pharm Sci 41:636–643CrossRefGoogle Scholar
  20. Kulkarni PV, Roney CA, Antich PP, Bonte FJ, Raghu AV, Aminabhavi TM (2010) Quinoline-n-butylcyanoacrylatebased nanoparticles for brain targeting for the diagnosis of Alzheimer’s disease. WIREs Nanomed Nanobiotechnol 2:35–47CrossRefGoogle Scholar
  21. Kumar S, Malick AW, Meltzer NM, Mouskountankis JD, Behl CR (1992) Studies of in-vitro skin permeation and retention of a leucotriene antagonist from topical vehicles with a hairless guinea pig model. J Pharm Sci 81:631–634CrossRefGoogle Scholar
  22. Lee PJ, Langer R, Shastri VP (2005) Role of n-methyl pyrrolidone in the enhancement of aqueous phase transdermal transport. J Pharm Sci 94:912–917CrossRefGoogle Scholar
  23. Lipoid GmbH (2017) Phospholipids. Accessed 3 Nov 2017
  24. Lopez-Pinto JM, Gonzalez-Rodriguez ML, Rabasco AM (2005) Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes. Int J Pharm 298:1–12CrossRefGoogle Scholar
  25. Mandawgade SD, Patravale VB (2008) Development of SLNs from natural lipids: application to topical delivery of tretinoin. Int J Pharm 363:132–138CrossRefGoogle Scholar
  26. Martin A, Swarbrick J, Cammarata A (1983) Physical pharmacy, 3rd edn. Lea and Febiger, Philadelphia, pp 445–468Google Scholar
  27. Marto J, Vitor C, Guerreiro A, Severino C, Eleutério C, Ascenso A, Simões S (2016) Ethosomes for enhanced skin delivery of griseofulvin. Colloids Surf B 146:616–623CrossRefGoogle Scholar
  28. Mbah CC, Builders PF, Attama AA (2014a) Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus. Exp Opin Drug Deliv 11(1):45–59CrossRefGoogle Scholar
  29. Mbah C, Builders P, Nzekwe I, Kunle O, Adikwu M, Attama A (2014b) Formulation and in vitro evaluation of pH-responsive ethosomes for vaginal delivery of metronidazole. J Drug Deliv Sci Technol 24(6):565–571CrossRefGoogle Scholar
  30. Merck Index (1989) Stearic, oleic and linoleic acids, 11th edn. 1107, 1192, 1319. Merck & Co., Inc., New JerseyGoogle Scholar
  31. Nguyen CA, Konan-Kouakou YN, Allemann E, Doelker E, Quintanar-Guerrero D, Fessi H, Gurny R (2006) Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating. AAPS Pharm Sci Tech 7(3):63.
  32. Saito Y, Sato T, Anazawa I (1989) Correlation between distribution of oxyethylene chains of nonionic surfactants and stability of cyclohexane droplets. Colloid Surf 40:107–114CrossRefGoogle Scholar
  33. Schreier H, Bouwstra J (1994) Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery. J Control Release 30:1–15CrossRefGoogle Scholar
  34. Semete-Makokotlela B, Kalombo L, Hayeshi R, Swai H (2011) Nanomedicine for improved efficacy of tuberculosis drugs. 4th ANDI Stakeholders Meeting 24–28 Oct., Addis AbabaGoogle Scholar
  35. Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S (2008) Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion. J Nanobiotechnol 6:8. CrossRefGoogle Scholar
  36. Shivanand P, Manish G, Viral D, Jarina F (2009) Transferosomes: a novel approach for transdermal drug delivery. Der Pharm Lett 1(2):143–150.
  37. Takano R, Sugano K, Higashida A, Hayashi Y, Machida M, Aso Y, Yamashita S (2006) Oral absorption of poorly water-soluble drugs: computer simulation of fraction absorbed in humans from a mini-scale dissolution test. Pharm Res 23:1144–1156CrossRefGoogle Scholar
  38. Touitou E (1996) Composition of applying active substances to or through the skin. US Patent, 5,716,638Google Scholar
  39. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M (2000) Ethosomes – novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release 65:403–418CrossRefGoogle Scholar
  40. United States Pharmacopoeia (USP) 26 (2003) Asian ed., United States Pharmacopoeial Convention, Inc, Pharmacopoeia Rockville, p 875Google Scholar
  41. Williams A (2003) Transdermal and topical drug delivery, 1st edn. Pharmaceutical Press, LondonGoogle Scholar
  42. Xiong GL, Quan D, Maibach HI (1996) Effects of penetration enhacers on in vitro percutaneous absorption of low molecular weight heparin through human skin. J Control Release 42:289–296CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2017

Authors and Affiliations

  • Chukwuemeka C. Mbah
    • 1
    Email author
  • Philip F. Builders
    • 2
  • Chukwuma O. Agubata
    • 1
  • Anthony A. Attama
    • 3
  1. 1.Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical SciencesUniversity of NigeriaNsukkaNigeria
  2. 2.Department of Pharmaceutical Technology and Raw Materials DevelopmentNational Institute for Pharmaceutical Research and Development (NIPRD)AbujaNigeria
  3. 3.Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical SciencesUniversity of NigeriaNsukkaNigeria

Personalised recommendations