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Thermoreversible-mucoadhesive Gel for nasal delivery of sumatriptan

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Abstract

The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF 127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34°C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29°C for 18% PF127 to 23.9°C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF 127 gel formulation of sumatriptan, with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

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References

  1. Fowler PA, Lacey LF, Thomas M, Keene ON, Tanner RJ, Baber NS. The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan.Eur Neurol. 1991; 31: 291–294.

    Article  CAS  PubMed  Google Scholar 

  2. Ryan R, Elkind A, Baker CC, Mullican W, DeBussey S, Asgharnejad M. Sumatriptan, nasal spray for the acute treatment of migraine: results of two clinical studies.Neurology. 1997; 49: 1225–1230.

    Article  CAS  PubMed  Google Scholar 

  3. Vyas TK, Babbar AK, Sharma RK, Singh S, Mirsa A. Preliminary brain-targeting studies on intranasal, mucoadhesive microemulsions of sumatriptan.AAPS PharmSciTech. 2006; 7: E8.

    Article  PubMed  Google Scholar 

  4. Zhou M, Donovan MD. Intranasal mucociliary clearance of putative bioadhesive polymer gels.Int J Pharm. 1996; 135: 115–125.

    Article  CAS  Google Scholar 

  5. Illum L. Bioadhesive formulations for nasal peptide delivery. In: Mathiowitz E, Chickering DE, Lehr CM, eds.Bioadhesive Drug Delivery Systems. New York, NY. Marcel Dekker, 1999: 507–562.

    Google Scholar 

  6. Majithiya RJ, Murthy RS. Chitosan-based mucoadhesive microspheres of clarithromycin as a delivery system for antibiotic to stomach.Curr Drug Deliv. 2005 2: 235–242.

    Article  CAS  PubMed  Google Scholar 

  7. D’Souza R, Mutalik S, Venkatesh M, Vidyasagar S, Udupa N. Insulin gel as an alternate to parenteral insulin: formulation, preclinical, and clinical studies.AAPS PharmSciTech. 2005; 6: E184-E189.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bromberg LE, Ron ES. Protein and peptide release from temperature-responsive gels and thermogelling polymer matrices.Adv Drug Deliv Rev. 1998; 31: 197–221.

    Article  CAS  PubMed  Google Scholar 

  9. Pisal SS, Paradkar AR, Mahadik KR, Kadam SS. Pluronic gels for nasal delivery of Vitamin B12. Part I: Preformulation study.Int J Pharm. 2004; 270: 37–45.

    Article  CAS  PubMed  Google Scholar 

  10. Schmolka IR. Artificial skin: preparation and properties of Pluronic F-127 gels for the treatment of burns.J Biomed Mater Res. 1972; 6: 571–582.

    Article  CAS  PubMed  Google Scholar 

  11. Choi HG, Oh YK, Kim CK. In situ gelling and mucoadhesive liquid suppository containing acetaminophen: enhanced bioavailability.Int J Pharm. 1998; 165: 23–32.

    Article  CAS  Google Scholar 

  12. Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design, characterization and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease.J Control Release. 2000; 67: 357–368.

    Article  CAS  PubMed  Google Scholar 

  13. Ch’ng HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers as platforms for oral controlled drug delivery II. Synthesis and evaluation of some swelling water-insoluble bioadhesive polymers.J Pharm Sci. 1985; 74: 339–405.

    Google Scholar 

  14. Lang S, Oschmann R, Traving B, Langguth P, Merkle HP. Transport and metabolic pathway of thymocartin (TP4) in excised bovine nasal mucosa.J Pharm Pharmacol. 1996; 48: 1190–1196.

    Article  CAS  PubMed  Google Scholar 

  15. Keck T, Leiacker R, Riechelmann H, Reittinger G. Temperature profile in the nasal cavity.Laryngoscope. 2000; 110: 651–654.

    Article  CAS  PubMed  Google Scholar 

  16. Kabanov AV, Batrakova, EV, Alakhov VU. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery.J Control Release. 2002; 82: 189–212.

    Article  CAS  PubMed  Google Scholar 

  17. Cabana A, AitKadi A, Juhasz J. Study of the gelation process of polyethylene oxide a-polypropylene oxide b-polyethylene oxide a copolymer (Poloxamer 407) aqueous solutionsJ Colloid Interface Sci. 1997; 190: 307–312.

    Article  CAS  PubMed  Google Scholar 

  18. Rassing J, Attwood D. Ultrasonic velocity and light scattering studies on polyoxyethylene-polyoxypropylene copolymer PF127 in aqueous, solution.Int J Pharm 1982; 13: 47–55.

    Article  CAS  Google Scholar 

  19. Efentakis, M, Koutlis A, Vlachou M. Development, and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems.AAPS PharmaSciTech. 2000; 1: E34.

    CAS  Google Scholar 

  20. Kunisawa J, Okudaira A, Tsutusmi Y, et al. Characterization of mucoadhesive microspheres for the induction of mucosal and systemic immune responses.Vaccine. 2000; 19: 589–594.

    Article  CAS  PubMed  Google Scholar 

  21. Wadell C, Bjork E, Camber O. Permeability, of porcine nasal mucosa correlated with human nasal absorption.Eur J Pharm Sci. 2003; 18: 47–53.

    Article  CAS  PubMed  Google Scholar 

  22. Chen G, Hoffman AS, Kabra B, Randeri K. Temperature-induced gelation Pluronic-g-poly(acrylic acid) graft copolymers for prolonged drug delivery to the eye. In: Harris JM, Zalips S, eds.Poly(ethylene glycol): Chemistry and Biological Applications. New York, NY. Oxford University Press USA; 1997: 441–451.

    Chapter  Google Scholar 

  23. Lue\en HL, Lehr CM, Rentel CO, et al. Bioadhesive polymers for the peroral delivery of peptide drugs.J Control Release. 1994; 29: 329–338.

    Article  Google Scholar 

  24. Lueßen HL, Rentel CO, Kotze AF, et al. Mucoadhesive polymers in peroral peptide drug delivery. IV. Polycarbophil and chitosan are potent enhancers of peptide transport acros intestinal mucosa in vitro.J Control Release. 1997; 45: 15–23.

    Article  Google Scholar 

  25. Bromberg L. Interactions among proteins and hydrophobically modified polyelectrolytes.J Pharm Pharmacol. 2001; 53: 541–547.

    Article  CAS  PubMed  Google Scholar 

  26. Bromberg L, Alakhov A. Effects of polyether-modified pol (acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers.J Control Release. 2003; 88: 11–22.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Drug Delivery Research Laboratory, Center of Relevance and Excellence in New Drug Delivery Systems (NDDS) Pharmacy Department, G. H. Patel Building, Donor’s Plaza, Fatehgunj, M. S. University of Baroda, 390002, Vadodara, Gujarat, India

    Rita J. Majithiya, Pradip K. Ghosh, Manish L. Umrethia & Rayasa S. R. Murthy

Authors
  1. Rita J. Majithiya
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  2. Pradip K. Ghosh
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  3. Manish L. Umrethia
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  4. Rayasa S. R. Murthy
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Correspondence to Rayasa S. R. Murthy.

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Published: August 4, 2006

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Majithiya, R.J., Ghosh, P.K., Umrethia, M.L. et al. Thermoreversible-mucoadhesive Gel for nasal delivery of sumatriptan. AAPS PharmSciTech 7, 67 (2006). https://doi.org/10.1208/pt070367

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