Skip to main content
SpringerLink
Log in

Formulation and Evaluation of Thermoreversible In Situ Nasal Gels Containing Mometasone Furoate for Allergic Rhinitis

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The purpose of the present work was to develop a mucoadhesive thermoreversible nasal gel with a tailored gelling temperature to provide the prolonged contact between mometasone furoate and the nasal mucosa and in order to prevent drainage of the formulation. For this purpose, in situ gel containing a thermogelling polymer poloxamer 407 (Pluronic® F-127) and a mucoadhesive polymer Carbopol® 974P NF was prepared. In this content, formulations were designed to have gelation temperature below 34°C to obtain gelation at intranasal cavity. Evaluation of the prepared in situ gels was carried out by the determination of sol-gel transition temperature, rheological and mechanical characteristics, mucoadhesion strength, drug content, physicochemical stability, in vitro release profiles, and ex vivo permeation across sheep nasal mucosa of formulations. Consequently, the in situ gel (CP5) which had favorable gelation temperature (30.1 ± 0.24°C), rheological and mechanical characteristics, in vitro release profile (T%100 180 min), and mucoadhesion strength (0.289 ± 0.0069 mJ) was developed. Consequently, the in situ gel system has been concluded as a promising approach in order to improve the therapeutic effects of intranasal mometasone furoate administration.

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

Similar content being viewed by others

References

  1. S-l C, X-w R, Q-z Z, Chen E, Xu F, Chen J, et al. In situ gel based on gellan gum as new carrier for nasal administration of mometasone furoate. Int J Pharm. 2009;365(1):109–15.

    Google Scholar 

  2. Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001;108(1):S2–8.

    Article  CAS  PubMed  Google Scholar 

  3. Berlucchi M, Pedruzzi B. Intranasal mometasone furoate for treatment of allergic rhinitis. Clinical Medicine Insights Therapeutics. 2010;2:761.

    Article  CAS  Google Scholar 

  4. Mandhane SN, Shah JH, Thennati R. Allergic rhinitis: an update on disease, present treatments and future prospects. Int Immunopharmacol. 2011;11(11):1646–62.

    Article  CAS  PubMed  Google Scholar 

  5. Dibildox J. Safety and efficacy of mometasone furoate aqueous nasal spray in children with allergic rhinitis: results of recent clinical trials. J Allergy Clin Immunol. 2001;108(1):S54–S8.

    Article  CAS  PubMed  Google Scholar 

  6. Hochhaus G. Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy. Clin Ther. 2008;30(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  7. Illum L, Jørgensen H, Bisgaard H, Krogsgaard O, Rossing N. Bioadhesive microspheres as a potential nasal drug delivery system. Int J Pharm. 1987;39(3):189–99.

    Article  CAS  Google Scholar 

  8. Gizurarson S. The relevance of nasal physiology to the design of drug absorption studies. Adv Drug Deliv Rev. 1993;11(3):329–47.

    Article  CAS  Google Scholar 

  9. Zaki NM, Awad GA, Mortada ND, ElHady SSA. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci. 2007;32(4):296–307.

    Article  CAS  PubMed  Google Scholar 

  10. Ruel-Gariepy E, Leroux J-C. In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm. 2004;58(2):409–26.

    Article  CAS  PubMed  Google Scholar 

  11. Peppas N, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000;50(1):27–46.

    Article  CAS  PubMed  Google Scholar 

  12. Koffi A, Agnely F, Ponchel G, Grossiord J. Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine. Eur J Pharm Sci. 2006;27(4):328–35.

    Article  CAS  PubMed  Google Scholar 

  13. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RFV. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm. 2010;75(2):186–93.

    Article  CAS  PubMed  Google Scholar 

  14. Schmolka IR. Artificial skin I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6(6):571–82.

    Article  CAS  PubMed  Google Scholar 

  15. Kim C-K, Lee S-W, Choi H-G, Lee M-K, Gao Z-G, Kim I-S, et al. Trials of in situ-gelling and mucoadhesive acetaminophen liquid suppository in human subjects. Int J Pharm. 1998;174(1):201–7.

    Article  CAS  Google Scholar 

  16. Copetti G, Grassi M, Lapasin R, Pricl S. Synergistic gelation of xanthan gum with locust bean gum: a rheological investigation. Glycoconj J. 1997;14(8):951–61.

    Article  CAS  PubMed  Google Scholar 

  17. Owen DH, Peters JJ, Katz DF. Rheological properties of contraceptive gels. Contraception. 2000;62(6):321–6.

    Article  CAS  PubMed  Google Scholar 

  18. Chang JY, Oh Y-K, H-g C, Kim YB, Kim C-K. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm. 2002;241(1):155–63.

    Article  CAS  PubMed  Google Scholar 

  19. Basu S, Bandyopadhyay AK. Development and characterization of mucoadhesive in situ nasal gel of midazolam prepared with Ficus carica mucilage. AAPS Pharm SciTech. 2010;11(3):1223–31.

    Article  CAS  Google Scholar 

  20. Bhandwalkar MJ, Avachat AM. Thermoreversible nasal in situ gel of venlafaxine hydrochloride: formulation, characterization, and pharmacodynamic evaluation. AAPS Pharm SciTech. 2013;14(1):101–10.

    Article  CAS  Google Scholar 

  21. Ourique AF, Contri RV, Guterres SS, Beck RCR, Pohlmann AR, Melero A, et al. Set-up of a method using LC-UV to assay mometasone furoate in pharmaceutical dosage forms. Química Nova. 2012;35(4):818–21.

    Article  CAS  Google Scholar 

  22. Viram P, Lumbhani A. Development and evaluation of ion-dependent in-situ nasal gelling systems of metoclopramide hydrochloride as an antimigraine model drug. International J Latest Res Sci Technology. 2012;1(2):80–9.

    Google Scholar 

  23. Sood S, Jawahar N, Jain K, Gowthamarajan K, Nainar MS. Olanzapine loaded cationic solid lipid nanoparticles for improved oral bioavailability. Curr Nanosci. 2013;9(1):26–34.

    CAS  Google Scholar 

  24. Sato H, Miyagawa Y, Okabe T, Miyajima M, Sunada H. Dissolution mechanism of diclofenac sodium from wax matrix granules. J Pharm Sci. 1997;86(8):929–34.

    Article  CAS  PubMed  Google Scholar 

  25. Illum L. Nasal delivery. The use of animal models to predict performance in man. J Drug Target. 1996;3(6):427–42.

    Article  CAS  PubMed  Google Scholar 

  26. Pund S, Rasve G, Borade G. Ex vivo permeation characteristics of venlafaxine through sheep nasal mucosa. Eur J Pharm Sci. 2013;48(1):195–201.

    Article  CAS  PubMed  Google Scholar 

  27. Shelke S, Shahi S, Jalalpure S, Dhamecha D, Shengule S. Formulation and evaluation of thermoreversible mucoadhesive in-situ gel for intranasal delivery of naratriptan hydrochloride. Journal of Drug Delivery Science and Technology. 2015;29:238–44.

    Article  CAS  Google Scholar 

  28. Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RS. Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan. AAPS Pharm SciTech. 2006;7(3):E80–E6.

    Article  Google Scholar 

  29. Singh RM, Kumar A, Pathak K. Thermally triggered mucoadhesive in situ gel of loratadine: β-cyclodextrin complex for nasal delivery. AAPS Pharm SciTech. 2013;14(1):412–24.

    Article  CAS  Google Scholar 

  30. Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur J Pharm Sci. 1998;6(2):105–12.

    Article  CAS  PubMed  Google Scholar 

  31. Shinde JV, Mali KK, Dias RJ, Havaldar VD, Mahajan NS. Insitu mucoadhesive nasal gels of metoclopramide hydrochloride: preformulation and formulation studies. J Pharm Res. 2008;1(1):88–96.

    CAS  Google Scholar 

  32. Basu S, Bandyopadhyay AK. Characterization of mucoadhesive nasal gels containing midazolam hydrochloride prepared from Linum usitatissimum L. mucilage. Braz J Pharm Sci. 2011;47(4):817–23.

    Article  CAS  Google Scholar 

  33. Tan YT, Peh KK, Al-Hanbali O. Effect of Carbopol and polyvinylpyrrolidone on the mechanical, rheological, and release properties of bioadhesive polyethylene glycol gels. AAPS Pharm SciTech. 2000;1(3):69–78.

    Article  Google Scholar 

  34. Bansal K, Rawat M, Jain A, Rajput A, Chaturvedi T, Singh S. Development of satranidazole mucoadhesive gel for the treatment of periodontitis. AAPS Pharm SciTech. 2009;10(3):716–23.

    Article  CAS  Google Scholar 

  35. Jones DS, Woolfson AD, Brown AF, O'Neill MJ. Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: in vitro release kinetics, syringeability, mechanical and mucoadhesive properties. J Control Release. 1997;49(1):71–9.

    Article  CAS  Google Scholar 

  36. Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res. 2011;2(4):215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems. AAPS Pharm SciTech. 2000;1(4):62–70.

    Article  Google Scholar 

  38. Ravi P, Aditya N, Patil S, Cherian L. Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization. Drug Deliv. 2015;22(7):903–10.

    Article  CAS  PubMed  Google Scholar 

  39. Desai SD, Blanchard J. In vitro evaluation of pluronic F127-based controlled-release ocular delivery systems for pilocarpine. J Pharm Sci. 1998;87(2):226–30.

    Article  CAS  PubMed  Google Scholar 

  40. Ryu J-M, Chung S-J, Lee M-H, Kim C-K, Shim C-K. Increased bioavailability of propranolol in rats by retaining thermally gelling liquid suppositories in the rectum. J Control Release. 1999;59(2):163–72.

    Article  CAS  PubMed  Google Scholar 

  41. Lu G, Jun HW. Diffusion studies of methotrexate in Carbopol and poloxamer gels. Int J Pharm. 1998;160(1):1–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the TUBITAK (The Scientific & Technological Research Council of Turkey) and the Research Fund of Istanbul University for providing financial assistance for carrying out the research work.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116, Beyazit, Istanbul, Turkey

    Ebru Altuntaş & Gülgün Yener

Authors
  1. Ebru Altuntaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gülgün Yener
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ebru Altuntaş.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Altuntaş, E., Yener, G. Formulation and Evaluation of Thermoreversible In Situ Nasal Gels Containing Mometasone Furoate for Allergic Rhinitis. AAPS PharmSciTech 18, 2673–2682 (2017). https://doi.org/10.1208/s12249-017-0747-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-017-0747-8

KEY WORDS

Search

Navigation