Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of a microemulsion-based gel formulation for topical drug delivery of diclofenac sodium

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

Abstract

The aim of the current research was to investigate the release of diclofenac sodium, a poorly water-soluble drug from different formulations in vitro. A microemulsion (ME) was prepared using caprylocaproyl polyoxyl-8 glycerides, diethylene glycol monoethyl ether, and propylene glycol monolaurate. For enhancing the viscosity, carbopol was used to form an ME-based gel. The prepared formulations were characterized for physical appearance, droplet size, zeta potential, refractive index, percentage transmittance, heating–cooling cycles, phase separation, pH, conductivity, viscosity, drug content, staining solubility test, transmission electron microscopy and in vitro drug release using Franz diffusion cells. The mean droplets size for ME and ME-based gel-systems were 114.4 ± 0.472, and 178 ± 2.46 nm respectively, whereas the zeta potential values were −33.3 ± 0.64 mV for the former and −33.0 ± 0.40 mV for the latter. No significant variations in the pH nor physical appearance alterations were observed while stability tests were performed. Further, TEM images for drug-loaded ME and the gel exhibited nano-droplets that were spherical in shape. The release rate of diclofenac sodium formulated as ME or as ME gel had the highest release values (76.67 ± 8.63%) and (69.28 ± 7.14%) after 6 h respectively. This was statistically significant (p < 0.0001) compared to the control and different marketed formulations or compounded preparations. The ME-based gel had a higher viscosity suitable for topical administration without dripping. The in vitro result suggested that ME systems are powerful topical vehicles for enhanced penetration of diclofenac sodium.

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

Similar content being viewed by others

References

  • Akhtar N, Talegaonkar S, Khar RK, Jaggi M (2013) Self-nanoemulsifying lipid carrier system for enhancement of oral bioavailability of etoposide by P-glycoprotein modulation: In vitro cell line and in vivo pharmacokinetic investigation. J Biomed Nanotechnol 9(7):1216–1229

    Article  CAS  PubMed  Google Scholar 

  • Altman RD, Dreiser R, Fisher CL, Chase WF, Dreher DS, Zacher J (2009) Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol 36(9):1991–1999

    Article  PubMed  Google Scholar 

  • Atlantic Pharmacy and compounding (2016) Topical pain preparations. http://www.atlanticcompounding.com/wp-content/themes/atlanticpharmaandcompounding/pdf/topical-pain-preparations.pdf. Accessed 15 Dec 2016

  • Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S (2009) Microemulsions as a surrogate carrier for dermal drug delivery. Drug Dev Ind Pharm 35(5):525–547

    Article  CAS  PubMed  Google Scholar 

  • B & B Pharmacy compounding & Health Care Center (2016) Pain management compounding. http://www.bbpharmacy.com/paincompounding.html. Accessed 15 Dec 2016

  • Banning M (2008) Topical diclofenac: clinical effectiveness and current uses in osteoarthritis of the knee and soft tissue injuries. Expert Opin Pharmacother 9(16):2921–2929

    Article  CAS  PubMed  Google Scholar 

  • Barakat N, Fouad E, Elmedany A (2011) Enhancement of skin permeation and anti-inflammatory effect of indomethacin using microemulsion. Asian J Pharm 5(3):141–149. doi:10.4103/0973-8398.91989

    Article  CAS  Google Scholar 

  • Barthel H, Halewood D (2009) Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Semin Arthritis Rheum 39(3):203–212

    PubMed  Google Scholar 

  • Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382(9894):769–779

    Article  CAS  PubMed  Google Scholar 

  • Bikkad ML, Nathani AH, Mandlik SK, Shrotriya SN, Ranpise NS (2014) Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery. J Liposome Res 24(2):113–123

    Article  CAS  PubMed  Google Scholar 

  • Biswal B, Karna N, Nayak J, Joshi V (2014) Formulation and evaluation of microemulsion based topical hydrogel containing lornoxicam. J Appl Pharm Sci 4(12):77–84

    Google Scholar 

  • Burnham R, Gregg R, Healy P, Steadward R (1998) The effectiveness of topical diclofenac for lateral epicondylitis. Clin J Sport Med 8(2):78–81

    Article  CAS  PubMed  Google Scholar 

  • Chauhan L, Muzaffar F, Lohia S (2013) Design, development and evaluation of topical microemulsion. Int J Pharm Pharm Sci 5(2):604–610

    Google Scholar 

  • Chen H, Chang X, Du D, Li J, Xu H, Yang X (2006) Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm 315(1):52–58

    Article  CAS  PubMed  Google Scholar 

  • Coneac G, Vlaia V, Olariu I, Muţ AM, Anghel DF, Ilie C et al (2015) Development and evaluation of new microemulsion-based hydrogel formulations for topical delivery of fluconazole. AAPS PharmSciTech 16(4):889–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delgado-Charro MB, Iglesias-Vilas G, Blanco-Méndez J, López-Quintela MA, Marty J, Guy RH (1997) Delivery of a hydrophilic solute through the skin from novel microemulsion systems. Eur J Pharm Biopharm 43(1):37–42. doi:10.1016/S0939-6411(96)00016-1

    Article  Google Scholar 

  • Fouad SA, Basalious EB, El-Nabarawi MA, Tayel SA (2013) Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: in vitro/in vivo evaluation. Int J Pharm 453(2):569–578

    Article  CAS  PubMed  Google Scholar 

  • Gallardo V, Zouaki Y, Parera A, Ruiz MA (2002) Effect of cellulosic polymer on the release of salicylates in topical formulations. React Funct Polym 50(1):33–40

    Article  CAS  Google Scholar 

  • Gannu R, Palem CR, Yamsani SK, Yamsani VV, Yamsani MR (2010) Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: formulation optimization, ex vivo and in vivo characterization. Int J Pharm 388(1):231–241. doi:10.1016/j.ijpharm.2009.12.050

    Article  CAS  PubMed  Google Scholar 

  • Grace D, Rogers J, Skeith K, Anderson K (1999) Topical diclofenac versus placebo: a double blind, randomized clinical trial in patients with osteoarthritis of the knee. J Rheumatol 26(12):2659–2663

    CAS  PubMed  Google Scholar 

  • Gupta S, Bansal R, Ali J, Gabrani R, Dang S (2014) Development and characterization of polyphenon 60 and caffeine microemulsion for enhanced antibacterial activity. BioMed Res Int. doi:10.1155/2014/932017

    Google Scholar 

  • Harwansh R, Rahman A, Dang J (2010) Microemulsion system for transdermal of diclofenac sodium for bioavailability enhancement. J Pharm Res 3(9):2182–2185

    CAS  Google Scholar 

  • Helal DA, El-Rhman DA, Abdel-Halim SA, El-Nabarawi MA (2012) Formulation and evaluation of fluconazole topical gel. Int J Pharm Pharm Sci 4(5):176–183

    CAS  Google Scholar 

  • Hu Z, Tawa R, Konishi T, Shibata N, Takada K (2001) A novel emulsifier, labrasol, enhances gastrointestinal absorption of gentamicin. Life Sci 69(24):2899–2910. doi:10.1016/S0024-3205(01)01375-3

    Article  CAS  PubMed  Google Scholar 

  • Khiljee S, Rehman N, Sarfraz M, Montazeri H, Lbenberg R, Khiljee T (2010) In vitro release of indian penny wort, walnut, and turmeric from topical preparations using two different types of membranes. Diss 17(4):27–32. doi:10.14227/DT170410P27

    CAS  Google Scholar 

  • Khiljee S, Rehman NU, Khiljee T, Loebenberg R, Ahmad RS (2015) Formulation and clinical evaluation of topical dosage forms of indian penny wort, walnut and turmeric in eczema. Pak J Pharm Sci 1(28):2001–2007

    Google Scholar 

  • Kogan A, Garti N (2006) Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci 123:369–385

    Article  PubMed  Google Scholar 

  • Kotagale NR, Patel CJ, Parkhe AP, Khandelwal HM, Taksande JB, Umekar MJ (2010) Carbopol 934-sodium alginate-gelatin mucoadhesive ondansetron tablets for buccal delivery: Effect of PH modifiers. Indian J Pharm Sci 72(4):471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kreilgaard M, Pedersen EJ, Jaroszewski JW (2000) NMR characterisation and transdermal drug delivery potential of microemulsion systems. J Control Release 69(3):421–433. doi:10.1016/S0168-3659(00)00325-4

    Article  CAS  PubMed  Google Scholar 

  • Lawrence MJ, Rees GD (2000) Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 45(1):89–121

    Article  CAS  PubMed  Google Scholar 

  • Lopes LB (2014) Overcoming the cutaneous barrier with microemulsions. Pharmaceutics 6(1):52–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Maxima Pharmaceuticals Inc. (2016) Transdermal delivery of medications. http://www.maximapharmaceuticals.com/English/physician.asp. Accessed 3 December 2016

  • Medisca (2012) In vitro skin study: optimized delivery of diclofenac sodium. https://www.medisca.com/Pages/Studies/pdf-files/white-papers/VersaPro%20Gel%20Base%20Flyer.pdf

  • Müller R, Radtke M, Wissing S (2002) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54(1):131–155

    Google Scholar 

  • Moghimipour E, Salimi A, Karami M, Isazadeh S (2013) Preparation and characterization of dexamethasone microemulsion based on pseudoternary phase diagram. Jundishapur J Nat Pharm Prod 8(3):105–112. doi:10.17795/jjnpp-9373

    Article  PubMed  PubMed Central  Google Scholar 

  • Nair B, Taylor-Gjevre R (2010) A review of topical diclofenac use in musculoskeletal disease. Pharmaceuticals 3(6):1892–1908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ng S, Rouse J, Sanderson F, Eccleston G (2012) The relevance of polymeric synthetic membranes in topical formulation assessment and drug diffusion study. Arch Pharm Res 35(4):579–593. doi:10.1007/s12272-012-0401-7

    Article  CAS  PubMed  Google Scholar 

  • Nikumbh KV, Sevankar SG, Patil MP (2015) Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen. Drug Deliv 22(4):509–515

    Article  CAS  PubMed  Google Scholar 

  • Novartis Consumer Health I (2006) Clinical pharmacology biopharmaceutics review(s) - FDA. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022122_ClinPharmR.pdf. Accessed 1 Jan 2016.

    Google Scholar 

  • Novartis Consumer Health I (2009) Voltaren® gel. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022122s006lbl.pdf. Accessed 25 March 2015.

    Google Scholar 

  • Özgüney IS, Karasulu HY, Kantarci G, Sözer S, Güneri T, Ertan G (2006) Transdermal delivery of diclofenac sodium through rat skin from various formulations. AAPS PharmSciTech 7(4):E45

    Article  Google Scholar 

  • Park K, Kim C (1999) Preparation and evaluation of flurbiprofen-loaded microemulsion for parenteral delivery. Int J Pharm 181(2):173–179. doi:10.1016/S0378-5173(99)00029-0

    Article  CAS  PubMed  Google Scholar 

  • PCCA (2013) A validated transdermal vehicle with superior results over PLO. http://professionalarts.com/wp-content/uploads/2013/07/Lipoderm-Studies-Booklet_2013.pdf. Accessed 23 December 2016

  • Peira E, Scolari P, Gasco MR (2001) Transdermal permeation of apomorphine through hairless mouse skin from microemulsions. Int J Pharm 226(1):47–51

    Article  CAS  PubMed  Google Scholar 

  • Rhee Y, Choi J, Park E, Chi S (2001) Transdermal delivery of ketoprofen using microemulsions. Int J Pharm 228(1):161–170

    Article  CAS  PubMed  Google Scholar 

  • Richards H, Thomas CP, Bowen JL, & Heard CM (2006) In-vitro transcutaneous delivery of ketoprofen and polyunsaturated fatty acids from a pluronic lecithin organogel vehicle containing fish oil. J Pharm Pharmacol 58(7):903–908

    Article  CAS  PubMed  Google Scholar 

  • Sanna V, Peana AT, Moretti MD (2009) Effect of vehicle on diclofenac sodium permeation from new topical formulations: in vitro and in vivo studies. Curr Drug Deliv 6(1):93–100

    Article  CAS  PubMed  Google Scholar 

  • Shafiq-un-Nabi S, Shakeel F, Talegaonkar S, Ali J, Baboota S, Ahuja A et al (2007) Formulation development and optimization using nanoemulsion technique: a technical note. Aaps Pharmscitech 8(2):E17

    Article  Google Scholar 

  • Shahzadi I, Masood M, Chowdhary F, Anjum A, Nawaz M, Maqsood I et al (2014) Microemulsion formulation for topical delivery of miconazole nitrate. Int J Pharm Sci Rev Res 2(24):30–36

    Google Scholar 

  • Shainhouse JZ, Grierson LM, Naseer Z (2010) A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee. Am J Ther 17(6):566–576

    Article  PubMed  Google Scholar 

  • Shalviri A, Sharma AC, Patel D, Sayani A (2011) Low-surfactant microemulsions for enhanced topical delivery of poorly soluble drugs. J Pharm Pharm Sci 14(3):315–324

    Article  CAS  PubMed  Google Scholar 

  • Shinde U, Pokharkar S, Modani S (2012) Design and evaluation of microemulsion gel system of nadifloxacin. Indian J Pharm Sci 74(3):237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh AK, Chaurasiya A, Singh M, Upadhyay SC, Mukherjee R, Khar RK (2008) Exemestane loaded self-microemulsifying drug delivery system (SMEDDS): development and optimization. Aaps Pharmscitech 9(2):628–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tandel H, Patel P, Jani P (2015) Preparation and study of efavirenz microemulsion drug delivery system for enhancement of bioavailability. Eur J Pharm Med Res 2(5):1156–1174

    Google Scholar 

  • Thakkar H, Nangesh J, Parmar M, Patel D (2011) Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system. J Pharm Bioallied Sci 3(3):442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thakkar PJ, Madan P, Lin S (2014) Transdermal delivery of diclofenac using water-in-oil microemulsion: formulation and mechanistic approach of drug skin permeation. Pharm Dev Technol 19(3):373–384. doi:10.3109/10837450.2013.788658

    Article  CAS  PubMed  Google Scholar 

  • The Medicine hope pharmacy, PCCA. (2009) Commonly requested pain management compounds. http://www.medicineshoppe.com/~/media/images/sites/the%20medicine%20shoppe/0279/pain%20management%20compounding%20ideas.ashx. Accessed 27 November 2016

  • Tugwell PS, Wells GA, Shainhouse JZ (2004) Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol 31(10):2002–2012

    CAS  PubMed  Google Scholar 

  • US Food and Drug Administration (1997) Guidance for industry: Dissolution testing of immediate release solid oral dosage forms. Center for Drug Evaluation and Research, Rockville

    Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge Taibah University, Madinah, Saudi Arabia for funding this project through the Drug Development and Innovation Centre at University of Alberta, Edmonton, Canada. The authors are also thankful to Gattefosse, for providing excipients for this study.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, AB, T6G 2E1, Canada

    Braa Hajjar, Kira-Isabel Zier, Shirzad Azarmi & Raimar Löbenberg

  2. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Punjab, Pakistan

    Nayab Khalid

Authors
  1. Braa Hajjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kira-Isabel Zier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nayab Khalid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shirzad Azarmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raimar Löbenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raimar Löbenberg.

Ethics declarations

Conflict of interest

This research work does not contain any studies with human and animal subjects performed by any of the authors. The authors (B. Hajjar, K. Zier, N. Khalid, S. Azarmi and R. Löbenberg) declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hajjar, B., Zier, KI., Khalid, N. et al. Evaluation of a microemulsion-based gel formulation for topical drug delivery of diclofenac sodium. J. Pharm. Investig. 48, 351–362 (2018). https://doi.org/10.1007/s40005-017-0327-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-017-0327-7

Keywords

Search

Navigation