Skip to main content

Advertisement

SpringerLink
Log in

Correlation Between Rheological Properties and In Vitro Drug Release from Penetration Enhancer-Loaded Carbopol® Gels

  • Original Article
  • Published:
Journal of Pharmaceutical Innovation Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the effect of commonly used penetration enhancers on the viscoelastic properties and in vitro drug release from topical gel formulations.

Methods

Three penetration enhancers, diethylene glycol monoethyl ether (Transcutol®-P, TC), propylene glycol (PG), and 70 % ethanol were selected in this study. The non-steroidal anti-inflammatory drug diclofenac sodium (DNa) was used as a model drug. DNa gels were prepared using the gelling agent Carbopol® 971P with or without different concentrations of the three penetration enhancers. Each gel formulation was characterized in terms of its viscoelastic properties (elastic or storage modulus G′ and viscous or loss modulus G″) using a controlled stress rheometer (CSR) and in vitro release using Franz diffusion cells.

Results

DNa gels containing TC, PG, and ethanol demonstrated a significant decrease in the viscoelastic properties compared to gels containing no penetration enhancers, and an enhancement in drug release. Gels containing TC at the highest tested concentration (40 %) exhibited the lowest viscoelastic properties and showed the highest enhancement in drug release. Both TC and ethanol showed a concentration-dependent effect in promoting steady-state flux values for DNa, unlike PG. DNa release kinetics from all gels followed super case II transport as fitted by the Korsmeyer–Peppas model.

Conclusions

Our results provide valuable insights into the mechanisms by which different penetration enhancers can modulate drug release from topical gels by altering the rheological properties of the gelling agent.

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. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev Supplement. 2012;64:128–37.

    Article  Google Scholar 

  2. Pathan IB, Setty CM. Chemical penetration enhancers for transdermal drug delivery systems. Trop J Pharm Res. 2009;8(2):173–9.

    Article  CAS  Google Scholar 

  3. Chen Y, Quan P, Liu X, Wang M, Fang L. Novel chemical permeation enhancers for transdermal drug delivery. Asian J Parm Sci. 2014;9(2):51–64.

    Google Scholar 

  4. Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21.

    Article  CAS  PubMed  Google Scholar 

  5. Alexander A, Dwivedi S, Giri TK, Saraf S, Saraf S, Tripathi DK. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J Control Release. 2012;164(1):26–40.

    Article  CAS  PubMed  Google Scholar 

  6. Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70.

    Article  PubMed  Google Scholar 

  7. Hirata K, Mohammed D, Hadgraft J, Lane ME. Influence of lidocaine hydrochloride and penetration enhancers on the barrier function of human skin. Int J Pharm. 2014;477(1–2):416–20.

    Article  CAS  PubMed  Google Scholar 

  8. Abd E, Namjoshi S. Y.H. Mohammed YH, Roberts MS, Grice JE. Synergistic skin penetration enhancer and nanoemulsion formulations promote the human epidermal permeation of caffeine and naproxen. J Pharm Sci. 2016;105(1):212–20.

    Article  CAS  PubMed  Google Scholar 

  9. Barry BW. Lipid-protein-partitioning theory of skin penetration enhancement. J Control Release. 1991;15(3):237–48.

    Article  CAS  Google Scholar 

  10. Fresno M, Ramırez A, Jiménez M. Systematic study of the flow behaviour and mechanical properties of Carbopol® Ultrez™ 10 hydroalcoholic gels. Eur J Pharm Biopharm. 2002;54(3):329–35.

    Article  CAS  PubMed  Google Scholar 

  11. Contreras M, Sanchez R. Application of a factorial design to the study of specific parameters of a Carbopol ETD 2020 gel. Part I. Viscoelastic parameters. Int J Pharm. 2002;234(1–2):139–47.

    Article  CAS  PubMed  Google Scholar 

  12. Li C, Liu C, Liu J, Fang L. Correlation between rheological properties, in vitro release, and percutaneous permeation of tetrahydropalmatine. AAPS PharmSciTech. 2011;12(3):1002–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Díez-Sales O, Garrigues T, Herraez J, Belda R, Martín-Villodre A, Herraez M. In vitro percutaneous penetration of acyclovir from solvent systems and Carbopol 971-P hydrogels: influence of propylene glycol. J Pharm Sci. 2005;94(5):1039–47.

    Article  PubMed  Google Scholar 

  14. Mura P, Faucci M, Bramanti G, Corti P. Evaluation of transcutol as a clonazepam transdermal permeation enhancer from hydrophilic gel formulations. Eur J Pharm Sci. 2000;9(4):365–72.

    Article  CAS  PubMed  Google Scholar 

  15. Hamed R, Basil M, AlBaraghthi T, Sunoqrot S, Tarawneh O. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies. Pharm Dev Technol. 2015;15:1–10.

    Google Scholar 

  16. Nguyen D, Li F, Li H, Wong BS, Low CY, Liu X, Kang L. Drug permeation through skin is inversely correlated with carrier gel rigidity. Mol Pharm. 2014;12(2):444–52.

    Article  PubMed  Google Scholar 

  17. Arunkumar S, Ashok P, Desai B, Shivakumar H. Effect of chemical penetration enhancer on transdermal iontophoretic delivery of diclofenac sodium under constant voltage. Journal of Drug Delivery Science and Technology. 2015;30(Part A):171–9.

    Article  CAS  Google Scholar 

  18. Uchida T, Kadhum WR, Kanai S, Todo H, Oshizaka T, Sugibayashi K. Prediction of skin permeation by chemical compounds using the artificial membrane, Strat-M™. Eur J of Pharm Sci. 2015;67:113–8.

    Article  CAS  Google Scholar 

  19. Rautio J, Nevalainen T, Taipale H, Vepsäläinen J, Gynther J, Laine K, Järvinen T. Piperazinylalkyl prodrugs of naproxen improve in vitro skin permeation. Eur J Pharm Sci. 2000;11(2):157–63.

    Article  CAS  PubMed  Google Scholar 

  20. Sultana N, Arayne MS, Naveed S. Simultaneous quantitation of captopril and NSAID's in API, dosage formulations and human serum by RP-HPLC. J Chin Chem Soc. 2010;57(1):62–7.

    Article  CAS  Google Scholar 

  21. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35.

    Article  CAS  Google Scholar 

  22. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60(4):110–1.

    CAS  PubMed  Google Scholar 

  23. Rudraraju VS, Wyandt CM. Rheology of microcrystalline cellulose and sodiumcarboxymethyl cellulose hydrogels using a controlled stress rheometer: part II. Int J Pharm. 2005;292(1–2):63–73.

    Article  CAS  PubMed  Google Scholar 

  24. Hyun K, Kim SH, Ahn KH, Lee SJ. Large amplitude oscillatory shear as a way to classify the complex fluids. J Non Newtonian Fluid Mech. 2002;107(1–3):51–65.

    Article  CAS  Google Scholar 

  25. Celli JP, Turner BS, Afdhal NH, Ewoldt RH, McKinley GH, Bansil R, Erramilli S. Rheology of gastric mucin exhibits a pH-dependent sol–gel transition. Biomacromolecules. 2007;8(5):1580–6.

    Article  CAS  PubMed  Google Scholar 

  26. Batheja P, Sheihet L, Kohn J, Singer AJ, Michniak-Kohn B. Topical drug delivery by a polymeric nanosphere gel: formulation optimization and in vitro and in vivo skin distribution studies. J Control Release. 2011;149(2):159–67.

    Article  CAS  PubMed  Google Scholar 

  27. Jones DS, Bruschi ML, de Freitas O, Gremião MPD, Lara EHG, Andrews GP. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int J Pharm. 2009;372(1–2):49–58.

    Article  CAS  PubMed  Google Scholar 

  28. van Vliet T. Rheology and fracture mechanics of foods: solids and solid-like materials. CRC Press; 2013. 213–216.

  29. Karadzovska, Riviere JE. Assessing vehicle effects on skin absorption using artificial membrane assays. Eur J of Pharm Sci. 2013;50(5):569–76.

    Article  CAS  Google Scholar 

  30. Joshi V, Brewster D, Colonero P. In vitro diffusion studies in transdermal research: a synthetic membrane model in place of human skin. 2012;12:40–2.

  31. Arellano A, Santoyo S, Martın C, Ygartua P. Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels. Eur J Pharm Sci. 1999;7(2):129–35.

    Article  CAS  PubMed  Google Scholar 

  32. Liu P, Kurihara-Bergstrom T, Good WR. Cotransport of estradiol and ethanol through human skin in vitro: understanding the permeant/enhancer flux relationship. Pharm Res. 1991;8(7):938–44.

    Article  CAS  PubMed  Google Scholar 

  33. Contreras M, Sanchez R. Application of a factorial design to the study of the flow behavior, spreadability and transparency of a Carbopol ETD 2020 gel. Part II Int J Pharm. 2002;234(1–2):149–57.

    Article  CAS  PubMed  Google Scholar 

  34. Kumar P, Sanghvi P, Collins CC. Comparison of diffusion studies of hydrocortisone between the Franz cell and the enhancer cell. Drug Dev Ind Pharm. 1993;19(13):1573–85.

    Article  Google Scholar 

  35. Kundu SC, Cameron AD, Meltzer NM, Quick TW. Development and validation of method for determination of in vitro release of retinoic acid from creams. Drug Dev Ind Pharm. 1993;19(4):425–38.

    Article  CAS  Google Scholar 

  36. Pena LE. Topical drug delivery formulations: gel dosage forms: theory, formulation, and processing. In: Osbome DW and Amann AH, editors. CRC Press; 1989. 381–388.

  37. Khodaverdi E, Tafaghodi M, Ganji F, Abnoos K, Naghizadeh H. In vitro insulin release from thermosensitive chitosan hydrogel. AAPS PharmSciTech. 2012;13(2):460–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cross SE, Pugh WJ, Hadgraft J, Roberts MS. Probing the effect of vehicles on topical delivery: understanding the basic relationship between solvent and solute penetration using silicone membranes. Pharm Res. 2001;18(7):999–1005.

    Article  CAS  PubMed  Google Scholar 

  39. Brazel CS, Peppas NA. Mechanisms of solute and drug transport in relaxing, swellable, hydrophilic glassy polymers. Polymer. 1999;40(12):3383–98.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan

    Rania Hamed & Tamadur Al Baraghthi

  2. Department of Pharmacy, Faculty of Pharmacy, Zarqa University, P.O. Box 132222, Zarqa, 13132, Jordan

    Ahlam Zaid Alkilani

  3. Department of Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, P.O. Box 19328, Amman, Jordan

    Rana Abu-Huwaij

Authors
  1. Rania Hamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamadur Al Baraghthi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahlam Zaid Alkilani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rana Abu-Huwaij
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rania Hamed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamed, R., Al Baraghthi, T., Alkilani, A.Z. et al. Correlation Between Rheological Properties and In Vitro Drug Release from Penetration Enhancer-Loaded Carbopol® Gels. J Pharm Innov 11, 339–351 (2016). https://doi.org/10.1007/s12247-016-9262-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12247-016-9262-9

Keywords

Search

Navigation