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Formulation and Evaluation of In Situ Gelling Systems for Intranasal Administration of Gastrodin

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Abstract

Gastrodin is the major bioactive constituent of the traditional Chinese drug “Tianma.” It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

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REFERENCES

  1. Ojemann LM, Nelson WL, Shin DS, Rowe AO, Buchanan RA. Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav. 2006;8:376–83.

    Article  PubMed  Google Scholar 

  2. Zhao H. Advance in clinical application of gastrodin. Strait Pharm J. 2009;21:29–31.

    Google Scholar 

  3. Zeng X, Zhang Y, Zhang S, Zheng X. A microdialysis study of effects of gastrodin on neurochemical changes in the ischemic/reperfused rat cerebral hippocampus. Biol Pharm Bull. 2007;30:801–4.

    Article  PubMed  CAS  Google Scholar 

  4. Guo Z, Tan T, Zhong Y, Wu C. Study of the mechanism of gastrodin and derivatives of gastrodigenin. J West Chin Univ Med Sci. 1991;22:79–82.

    CAS  Google Scholar 

  5. Wang Q, Chen G, Zeng S. Pharmacokinetics of Gastrodin in rat plasma and CSF after i.n. and i.v. Int J Pharm. 2007;341:20–5.

    Article  PubMed  CAS  Google Scholar 

  6. Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci. 2000;11:1–18.

    Article  PubMed  CAS  Google Scholar 

  7. Watts P, Smith A. PecSys: in situ gelling system for optimised nasal drug delivery. Expert Opin Drug Deliv. 2009;6:543–52.

    Article  PubMed  CAS  Google Scholar 

  8. Nagarwal RC, Pandit JK. Phase transition system: novel oral in-situ gel. Curr Drug Deliv. 2008;5:282–9.

    Article  PubMed  CAS  Google Scholar 

  9. Jansson B, Hagerstrom H, Fransen N, Edsman K, Bjork E. The influence of gellan gum on the transfer of fluorescein dextran across rat nasal epithelium in vivo. Eur J Pharm Biopharm. 2005;59:557–64.

    Article  PubMed  CAS  Google Scholar 

  10. Balasubramaniam J, Kant S, Pandit JK. In vitro and in vivo evaluation of the Gelrite gellan gum-based ocular delivery system for indomethacin. Acta Pharm. 2003;53:251–61.

    PubMed  CAS  Google Scholar 

  11. Kubo W, Miyazaki S, Attwood D. Oral sustained delivery of paracetamol from in situ-gelling gellan and sodium alginate formulations. Int J Pharm. 2003;258:55–64.

    Article  PubMed  CAS  Google Scholar 

  12. Narayana RC, Harish NM, Gulzar AM, Prabhakara P, Singh AK, Subrahmanyam EV. Formulation and in vitro evaluation of in situ gels containing secnidazole for vaginitis. Yakugaku Zasshi. 2009;129:569–74.

    Article  PubMed  CAS  Google Scholar 

  13. Funami T, Noda S, Nakauma M, Ishihara S, Takahashi R, Al-Assaf S, et al. Molecular structures of gellan gum imaged with atomic force microscopy in relation to the rheological behavior in aqueous systems in the presence or absence of various cations. J Agric Food Chem. 2008;56:8609–18.

    Article  PubMed  CAS  Google Scholar 

  14. Cao SL, Ren XW, Zhang QZ, 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;365:109–15.

    Article  PubMed  CAS  Google Scholar 

  15. Lorin MI, Gaerlan PF, Mandel ID. Quantitative composition of nasal secretions in normal subjects. J Lab Clin Med. 1972;80:275–81.

    PubMed  CAS  Google Scholar 

  16. Mei D, Mao S, Sun W, Wang Y, Kissel T. Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats. Eur J Pharm Biopharm. 2008;70:874–81.

    Article  PubMed  CAS  Google Scholar 

  17. Hirai S, Yashiki T, Matsuzawa T, Mima H. Absorption of drugs from the nasal mucosa of rat. Int J Pharm. 1981;7:317–25.

    Article  CAS  Google Scholar 

  18. Lu Y, Chen X, Du S, Wu Q, Yao Z, Zhai Y. The in situ and in vivo study on enhancing effect of borneol in nasal absorption of Geniposide in rats. Arch Pharm Res. 2010;33:691–6.

    Article  PubMed  CAS  Google Scholar 

  19. Cai Z, Hou S, Li Y, Zhao B, Yang Z, Xu S, et al. Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration. J Drug Target. 2008;16:178–84.

    Article  PubMed  CAS  Google Scholar 

  20. Tao T, Zhao Y, Yue P, Dong WX, Chen QH. Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration. Acta Pharm Sin. 2006;41:1104–10.

    CAS  Google Scholar 

  21. Guinee TP, Feeney EP, Auty MA, Fox PF. Effect of pH and calcium concentration on some textural and functional properties of mozzarella cheese. J Dairy Sci. 2002;85:1655–69.

    Article  PubMed  CAS  Google Scholar 

  22. Asai K, Morishita M, Katsuta H, Hosoda S, Shinomiya K, Noro M, et al. The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa. Int J Pharm. 2002;246:25–35.

    Article  PubMed  CAS  Google Scholar 

  23. Jiang XG, Lu X, Cui JB, Qiu L, Xi NZ. Studies on octanol-water partition coefficient and nasal drug absorption. Acta Pharm Sin. 1997;32:458–60.

    CAS  Google Scholar 

  24. Illum L. Nasal drug delivery—possibilities, problems and solutions. J Control Release. 2003;87:187–98.

    Article  PubMed  CAS  Google Scholar 

  25. Choi HG, Jung JH, Ryu JM, Yoon SJ, Oh YK, Kim CK. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm. 1998;165:33–44.

    Article  CAS  Google Scholar 

  26. Wei G, Xu H, Ding PT, Li SM, Zheng JM. Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies. J Control Release. 2002;83:65–74.

    Article  PubMed  CAS  Google Scholar 

  27. Chung H, Dong H. Synthesis and characterisation of pluronic grafted chitosan copolymer as a novel injectable biomaterial. Curr Appl Phys. 2005;5:485–8.

    Article  Google Scholar 

  28. Mao R, Tang J, Swanson BG. Water holding capacity and microstructure of gellan gels. Carbohydr Polym. 2001;46:365–71.

    Article  CAS  Google Scholar 

  29. Lim ST, Martin GP, Berry DJ, Brown MB. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release. 2000;66:281–92.

    Article  PubMed  CAS  Google Scholar 

  30. Edsman K, Carlfors J, Harju K. Rheological evaluation and ocular contact time of some carbomer gels for ophthalmic use. Int J Pharm. 1996;137:233–41.

    Article  CAS  Google Scholar 

  31. Shusterman D. Toxicology of nasal irritants. Curr Allergy Asthma Rep. 2003;3:258–65.

    Article  PubMed  Google Scholar 

  32. Merkus FW, Verhoef JC, Schipper NG, Marttin E. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev. 1998;29:13–38.

    Article  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (no. 30902009) and Guangdong Natural Science Foundation (no. 10451008901004959).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China

    Zheng Cai & Zhongqiu Liu

  2. Institute of Pharmaceutical Research, Kunming Pharmaceutical Co. Ltd., Kunming, China

    Zheng Cai & Zhaoxiang Yang

  3. West China School of Pharmacy, Sichuan University, Chengdu, China

    Xiangrong Song & Shixiang Hou

  4. Guangzhou Baiyunshan Pharmaceutical General Factory, Guangzhou, China

    Feng Sun

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  1. Zheng Cai
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Correspondence to Zhongqiu Liu.

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Cai, Z., Song, X., Sun, F. et al. Formulation and Evaluation of In Situ Gelling Systems for Intranasal Administration of Gastrodin. AAPS PharmSciTech 12, 1102–1109 (2011). https://doi.org/10.1208/s12249-011-9678-y

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  • DOI: https://doi.org/10.1208/s12249-011-9678-y

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