Advertisement

Lidocaine Microemulsion-Laden Organogels as Lipid-Based Systems for Topical Delivery

  • Rania HamedEmail author
  • Ahmad Farhan
  • Rana Abu-Huwaij
  • Nouf N. Mahmoud
  • Areej Kamal
Original Article
  • 13 Downloads

Abstract

Purpose

Conventional organogel and microemulsion-laden organogels (microemulsion organogels) were developed to deliver the lipophilic drug, lidocaine, topically.

Methods

Optimized formulations of lidocaine microemulsions of oil, water, and surfactant:cosurfactant (Tween® 20:ethanol), at ratios 4:1 and 2:1 v/v, were selected based on the droplet size and physical stability of microemulsions. Microemulsions were then loaded into organogels. Lidocaine conventional organogel was prepared without the addition of microemulsion and used as a reference. The rheological properties and release profiles of lidocaine organogels were investigated.

Results

Lidocaine conventional and microemulsion organogels displayed viscoelastic properties with more elastic behavior. Lidocaine conventional organogel exhibited the highest viscoelastic properties and lowest rate of release, whereas microemulsion organogel containing Tween® 20:ethanol (4:1 v/v) exhibited lower viscoelastic properties and higher rate of release compared to those of microemulsion organogel containing Tween® 20:ethanol (2:1 v/v).

Conclusion

Type and composition of organogels dictated the viscoelastic properties and rate of release of lidocaine.

Keywords

Microemulsion Organogels Rheology Controlled-release Topical delivery 

Notes

Funding Information

This project was financially supported by the Deanship of Academic Research and Graduate Studies at Al-Zaytoonah University of Jordan.

Compliance with Ethical Standards

Informed consent was obtained from the donor for study participation and the experimental protocols were approved by Al-Zaytoonah University of Jordan Research Ethics Committee (ZUJ-RES 2018/64/04) in adherence to Helsinki Guidelines.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Santana PRC. Use of subcutaneous local anaesthetic in venous catheters channelling for reducing pain. Int J Nurs. 2015;2(2):179–86.Google Scholar
  2. 2.
    Negi P, Singh B, Sharma G, Beg S, Katare OP. Biocompatible lidocaine and prilocaine loaded-nanoemulsion system for enhanced percutaneous absorption: QbD-based optimisation, dermatokinetics and in vivo evaluation. J Microencapsul. 2015;32(5):419–31.Google Scholar
  3. 3.
    Pathak P, Nagarsenker M. Formulation and evaluation of lidocaine lipid nanosystems for dermal delivery. AAPS PharmSciTech. 2009;10(3):985–92.Google Scholar
  4. 4.
    Abu-Huwaij R, Assaf S, Salem M, Sallam A. Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization. Drug Dev Ind Pharm. 2007;33(8):855–64.Google Scholar
  5. 5.
    Dogrul A, Arslan SA, Tirnaksiz F. Water/oil type microemulsion systems containing lidocaine hydrochloride: in vitro and in vivo evaluation. J Microencapsul. 2014;31(5):448–60.Google Scholar
  6. 6.
    Carlfors J, Blute I, Schmidt V. Lidocaine in microemulsion—a dermal delivery system. J Dispers Sci Technol. 1991;12(5–6):467–82.Google Scholar
  7. 7.
    Zhu X, Li G, Zeng K, Cheng Z. Preparation of lidocaine nanoemulsion and its transdermal absorption by rat skin ex vivo. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30(3):451–4.Google Scholar
  8. 8.
    Mou D, Chen H, Du D, Mao C, Wan J, Xu H, et al. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm. 2008;353(1–2):270–6.Google Scholar
  9. 9.
    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. 2016;21(8):980–9.Google Scholar
  10. 10.
    Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer. 2008;49(8):1993–2007.Google Scholar
  11. 11.
    Bramwell BL, Williams LA. The use of pluronic lecithin organogels in the transdermal delivery of drugs. Int J Pharm Compd. 2012;16(1):62–3.Google Scholar
  12. 12.
    Bakonyi M, Gácsi A, Kovács A, Szűcs M-B, Berkó S, Csányi E. Following-up skin penetration of lidocaine from different vehicles by Raman spectroscopic mapping. J Pharm Biomed Anal. 2018;154:1–6.Google Scholar
  13. 13.
    McClements DJ. Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter. 2012;8(6):1719–29.Google Scholar
  14. 14.
    Kale SN, Deore SL. Emulsion micro emulsion and nano emulsion: a review. Syst Rev Pharm. 2017;8(1):39.Google Scholar
  15. 15.
    Anton N, Vandamme TF. Nano-emulsions and micro-emulsions: clarifications of the critical differences. Pharm Res. 2011;28(5):978–85.Google Scholar
  16. 16.
    Shukla T, Upmanyu N, Agrawal M, Saraf S, Saraf S, Alexander A. Biomedical applications of microemulsion through dermal and transdermal route. Biomed Pharmacother. 2018;108:1477–94.Google Scholar
  17. 17.
    Hamed R, AbuRezeq AA, Tarawneh O. Development of hydrogels, oleogels, and bigels as local drug delivery systems for periodontitis. Drug Dev Ind Pharm. 2018;1–10.Google Scholar
  18. 18.
    Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm. 2014;40(4):433–40.Google Scholar
  19. 19.
    Alkilani AZ, Hamed R, Al-Marabeh S, Kamal A, Abu-Huwaij R, Hamad I. Nanoemulsion-based film formulation for transdermal delivery of carvedilol. J Drug Delivery Sci Technol. 2018;46:122–8.Google Scholar
  20. 20.
    Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech. 2009;10(1):69–76.Google Scholar
  21. 21.
    Ali MS, Alam MS, Alam N, Siddiqui MR. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy. Iran J Pharm Res. 2014;13(4):1125.Google Scholar
  22. 22.
    Kumar N, Mandal A. Surfactant stabilized oil-in-water nanoemulsion: stability, interfacial tension and rheology study for enhanced oil recovery application. Energy Fuel. 2018;32:6452–66.Google Scholar
  23. 23.
    Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007;66(2):227–43.Google Scholar
  24. 24.
    Ricci Júnior E, Bentley MVLB, Marchetti JM. HPLC assay of lidocaine in in vitro dissolution test of the Poloxamer 407 gels. Braz J Pharm Sci. 2002;38(1):107–11.Google Scholar
  25. 25.
    Guideline IHT, editor. Validation of analytical procedures: text and methodology Q2 (R1). Geneva: International Conference on Harmonization; 2005.Google Scholar
  26. 26.
    Mahmoud NN, Alkilany AM, Dietrich D, Karst U, Al-Bakri AG, Khalil EA. Preferential accumulation of gold nanorods into human skin hair follicles: effect of nanoparticle surface chemistry. J Colloid Interface Sci. 2017;503:95–102.Google Scholar
  27. 27.
    Mahmoud NN, Al-Qaoud KM, Al-Bakri AG, Alkilany AM, Khalil EA. Colloidal stability of gold nanorod solution upon exposure to excised human skin: effect of surface chemistry and protein adsorption. Int J Biochem Cell Biol. 2016;75:223–31.Google Scholar
  28. 28.
    Cojocaru V, Ranetti AE, Hinescu LG, Ionescu M, Cosmescu C, Poștoarcă AG, et al. Formulation and evaluation of in vitro release kinetics of Na3CaDTPA decorporation agent embedded in microemulsion-based gel formulation for topical delivery. FARMACIA. 2015;63(5):656–64.Google Scholar
  29. 29.
    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.Google Scholar
  30. 30.
    Peppas N. Analysis of Fickian and non-Fickian drug release from polymers. 1985.Google Scholar
  31. 31.
    Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5(1):37–42.Google Scholar
  32. 32.
    Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release. 1987;5(1):23–36.Google Scholar
  33. 33.
    Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev. 1997;25(1):47–58.Google Scholar
  34. 34.
    Borhade V, Pathak S, Sharma S, Patravale V. Clotrimazole nanoemulsion for malaria chemotherapy. Part I: preformulation studies, formulation design and physicochemical evaluation. Int J Pharm. 2012;431(1–2):138–48.Google Scholar
  35. 35.
    Rajpoot P, Bali V, Pathak K. Anticancer efficacy, tissue distribution and blood pharmacokinetics of surface modified nanocarrier containing melphalan. Int J Pharm. 2012;426(1–2):219–30.Google Scholar
  36. 36.
    Tayel SA, El-Nabarawi MA, Tadros MI, Abd-Elsalam WH. Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits. Int J Pharm. 2013;443(1–2):293–305.Google Scholar
  37. 37.
    Kale NJ, Allen LV Jr. Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants. Int J Pharm. 1989;57(2):87–93.Google Scholar
  38. 38.
    Wang S, Chen P, Zhang L, Yang C, Zhai G. Formulation and evaluation of microemulsion-based in situ ion-sensitive gelling systems for intranasal administration of curcumin. J Drug Target. 2012;20(10):831–40.Google Scholar
  39. 39.
    Hamed R, Al Baraghthi T, Alkilani AZ, Abu-Huwaij R. Correlation between rheological properties and in vitro drug release from penetration enhancer-loaded Carbopol® gels. J Pharm Innov. 2016;11(4):339–51.Google Scholar
  40. 40.
    Sagiri S, Singh VK, Pal K, Banerjee I, Basak P. Stearic acid based oleogels: a study on the molecular, thermal and mechanical properties. Mater Sci Eng C. 2015;48:688–99.Google Scholar
  41. 41.
    Rogers MA, Strober T, Bot A, Toro-Vazquez JF, Stortz T, Marangoni AG. Edible oleogels in molecular gastronomy. Int J Gastron Food Sci. 2014;2(1):22–31.Google Scholar
  42. 42.
    Yang J, Gong C, Shi F-K, Xie X-M. High strength of physical hydrogels based on poly (acrylic acid)-g-poly (ethylene glycol) methyl ether: role of chain architecture on hydrogel properties. J Phys Chem B. 2012;116(39):12038–47.Google Scholar
  43. 43.
    Matsumura Y, Kang I-J, Sakamoto H, Motoki M, Mori T. Filler effects of oil droplets on the viscoelastic properties of emulsion gels. Food Hydrocoll. 1993;7(3):227–40.Google Scholar
  44. 44.
    Geremias-Andrade IM, Souki NP, Moraes IC, Pinho SC. Rheology of emulsion-filled gels applied to the development of food materials. Gels. 2016;2(3):22.Google Scholar
  45. 45.
    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 Pharm Sci. 2015;67:113–8.Google Scholar
  46. 46.
    Hamed R, Al Baraghthi T, Sunoqrot S. Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release. Pharm Dev Technol. 2016a;1–11.  https://doi.org/10.1080/10837450.2016.1257022.
  47. 47.
    Wato K, Hara T, Yamana K, Nakao H, Inagi T, Terada K. An insight into the role of barrier related skin proteins. Int J Pharm. 2012;427(2):293–8.Google Scholar
  48. 48.
    Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2012;64:128–37.Google Scholar
  49. 49.
    Abd E, Benson HA, Roberts MS, Grice JE. Minoxidil skin delivery from nanoemulsion formulations containing eucalyptol or oleic acid: enhanced diffusivity and follicular targeting. Pharmaceutics. 2018;10(1):19.Google Scholar
  50. 50.
    Hussain A, Singh VK, Singh OP, Shafaat K, Kumar S, Ahmad FJ. Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of amphotericin B. Drug Deliv. 2016;23(8):3101–10.Google Scholar
  51. 51.
    Sawant PD, Luu D, Ye R, Buchta R. Drug release from hydroethanolic gels. Effect of drug’s lipophilicity (log P), polymer–drug interactions and solvent lipophilicity. Int J Pharm. 2010;396(1–2):45–52.Google Scholar
  52. 52.
    Tampucci S, Burgalassi S, Chetoni P, Monti D. Cutaneous permeation and penetration of sunscreens: formulation strategies and in vitro methods. Cosmetics. 2018;5(1):1.Google Scholar
  53. 53.
    Hagen M, Baker M. Skin penetration and tissue permeation after topical administration of diclofenac. Curr Med Res Opin. 2017;33(9):1623–34.Google Scholar
  54. 54.
    Sagiri SS, Kasiviswanathan U, Shaw GS, Singh M, Anis A, Pal K. Effect of sorbitan monostearate concentration on the thermal, mechanical and drug release properties of oleogels. Korean J Chem Eng. 2016;33(5):1720–7.Google Scholar
  55. 55.
    Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm. 2006;315(1–2):52–8.Google Scholar
  56. 56.
    Karasulu HY. Microemulsions as novel drug carriers: the formation, stability, applications and toxicity. Expert Opin Drug Deliv. 2008;5(1):119–35.Google Scholar
  57. 57.
    O'Sullivan CM, Barbut S, Marangoni AG. Edible oleogels for the oral delivery of lipid soluble molecules: composition and structural design considerations. Trends Food Sci Technol. 2016;57:59–73.Google Scholar
  58. 58.
    Aburahma MH, Badr-Eldin SM. Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals. Exp Opin Drug Deliv. 2014;11(12):1865–83.Google Scholar
  59. 59.
    Sapei L, Sandy I, Ray M (eds). The effect of different concentrations of tween-20 combined with rice husk silica on the stability of o/w emulsion: a kinetic study. IOP Conference Series: Materials Science and Engineering. IOP Publishing, 2017.Google Scholar
  60. 60.
    Aguda R, Chen C-C. Solubility of nutraceutical compounds in generally recognized as safe solvents at 298 k. Int J Chem Eng Appl. 2016;7(5):289–94.Google Scholar
  61. 61.
    Baboota S, Alam MS, Sharma S, Sahni JK, Kumar A, Ali J. Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis. Int J Pharm Investig. 2011;1(3):139–47.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, Faculty of PharmacyAl-Zaytoonah University of JordanAmmanJordan
  2. 2.Department of Pharmaceutics & Pharmaceutical Technology, Faculty of PharmacyAl-Ahliyya Amman UniversityAmmanJordan

Personalised recommendations