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Nasal in situ gel containing hydroxy propyl β-cyclodextrin inclusion complex of artemether: development and in vitro evaluation

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Abstract

The objective of the present investigation was to explore the formulation and evaluation of in situ gel for the nasal delivery of artemether (ARM), a poorly water-soluble antimalarial agent using temperature induced gelation technique using Pluronic with mucoadhesive polymer Hydroxy Propyl Methyl Cellulose (HPMC) K4M in different ratios. Initially, due to low water solubility, an inclusion complex of the antimalarial artemether (ARM) in hydroxypropyl-β-cyclodextrin (HPβCD) was prepared and characterized. The in situ gels so prepared were characterized for its gelation properties, viscosity, gel strength, mucoadhesion, drug content, drug release rate and for its histopathological studies. Pluronic and HPMC based in situ gel (PLH2) showed the effective gelation, viscosity, gel strength and drug release properties along with good mucoadhesive strength, it is further subjected for stability studies carried out at 30 ± 2 °C and 60 ± 5% RH for 90 days in order to know the influence of temperature and relative humidity on drug content and on drug release profile. Histological examination of formulations did not show any remarkable damage to nasal mucosa. The formulation also retained the good stability at accelerated conditions over the period of 90 days. Owing to these properties it can be used as an effective delivery system for the nasal route. These in situ gelling systems would be definitely useful for cerebral malaria.

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References

  1. Balint, G.A.: Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol. Ther. 90, 261–265 (2001)

    Article  CAS  Google Scholar 

  2. Baker, J.K., Yarber, R.H., Hufford, C.D., Lee, I.S., Elsohly, H.N., McChesney, J.D.: Thermospray mass spectroscopy/high performance liquid chromatographic identification of the metabolites formed from arteether using a rat liver microsome preparation. Biomed. Environ. Mass. Spectrom. 18, 337–351 (1988)

    Article  Google Scholar 

  3. Balasubramaniam, J., Kant, S., Pandit, J.K.: In vitro and in vivo evaluation of the Gelrite® gellan gum-based ocular delivery system for indomethacin. Acta Pharm. 53, 251–261 (2003)

    CAS  Google Scholar 

  4. Behl, C.R., Harper, N.J., Pei, J.Y.: A general method of accessing skin permeatin enhancement mechanisms and optimization. In: Hsies, D.S., (eds.) Drug permeation enhancement: theory and applications, 1st edn, p. 115. New York, NY: Marcel Dekker Inc (1994)

  5. Yang, B., Lin, J., Chen, Y., Liu, Y.: Artemether/hydroxypropyl-b cyclodextrin host–guest system: characterization, phase-solubility and inclusion mode. Bioorg. Med. Chem. 17, 6311–6317 (2009)

    Article  CAS  Google Scholar 

  6. Brewster, M.E., Loftsson, T.: The use of chemically modified cyclodextrins in the development of formulations for chemical delivery systems. Pharmazie 57, 94 (2002)

    CAS  Google Scholar 

  7. Bromberg, L.E., Ron, E.S.: Protein and peptide release from temperature responsive gels and thermogelling polymer matrices. Adv. Drug Deliv. Rev. 31, 197–221 (1998)

    Article  CAS  Google Scholar 

  8. Castronuovo, G., Niccoli, M.: Thermodynamics of inclusion complexes of natural and modified cyclodextrins with propanolol in aqueous solution at 298 K. Bioorg. Med. Chem. 14, 3883–3887 (2006)

    Article  CAS  Google Scholar 

  9. Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present, future. Nat. Rev. Drug Discov. 3, 1023 (2004)

    Article  CAS  Google Scholar 

  10. Desai, J., Alexander, K., Riga, A.: Characterization of polymeric dispersions of dimenhydrinate in ethyl cellulose for controlled release. Int. J. Pharm. 308, 115–123 (2006)

    Article  CAS  Google Scholar 

  11. Duchene, D., Wouessidjewe, D., Poncel, G.: Cyclodextrins and carrier systems. J. Control. Release 62, 263–268 (1999)

    Article  CAS  Google Scholar 

  12. Edsman, K., Carlfors, J., Petersson, R.: Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur. J. Pharm. Sci. 6, 105–112 (1998)

    Article  CAS  Google Scholar 

  13. Foley, M., Tilley, L.: Qinghaosu (artemisinin): an antimalarial drug from China. Int. J. Parasitol. 27, 213 (1997)

    Article  Google Scholar 

  14. Graff, C.L., Pollack, G.M.: Nasal drug administration: potential for targeted central nervous system delivery. J. Pharm. Sci. 94, 1187–1195 (2005)

    Article  CAS  Google Scholar 

  15. Greenwood, B., Mutabingwa, T.: Malaria in 2002. Nature 415, 670–672 (2002)

    Article  CAS  Google Scholar 

  16. Gonjari, I.D., Kasture, P.V.: Temperature induced in situ mucoadhesive gel of Tramadol hydrochlioride for nasal drug delivery. J. Pharm. Res. 6(2), 89–93 (2007)

    CAS  Google Scholar 

  17. Gould, S., Scott, R.C.: 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD): a toxicology review. Food Chem. Toxicol. 43, 1451 (2005)

    Article  CAS  Google Scholar 

  18. Hien, T.T., Davis, T.M., Chuong, L.V., Ilett, K.F., Sinh, D.X., Phu, N.H., Agus, C., Chiswell, G.M., White, N.J., Farrar, J.: Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria. Antimicrob. Agents Chemother. 48, 4234–4239 (2004)

    Article  CAS  Google Scholar 

  19. Irie, T., Uekama, K.: Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J. Pharm. Sci. 86, 147 (1997)

    Article  CAS  Google Scholar 

  20. Jiang, X., et al.: A novel nasal delivery system of a Chinese traditional medicine, Radix Bupleuri, based on the concept of ion-activated in situ gel. Arch. Pharm. Res. 30(8), 1014–1019 (2007). http://apr.psk.or.kr

    Google Scholar 

  21. Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Tübachova, I., Eberl, M., Zeider, J., Liechtenthaler, H.K., Soldati, D., Beck, E.: Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285, 1573 (1999)

    Article  CAS  Google Scholar 

  22. Kiechel, J. R., Malmison, R.: Nasal compositions. US Patent: 4,885,305 (1989)

  23. Klayman, D.: Qinghaosu (artemisinin). An antimalarial drug from China. Science 228, 1049–1055 (1989)

  24. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)

    Article  CAS  Google Scholar 

  25. Loftsson, T., Järvinen, T.: Cyclodextrins in ophthalmic drug delivery. Adv. Drug Deliv. Rev. 36, 59 (1999)

    Article  Google Scholar 

  26. Maggs, J.L., Bishop, L.P.D., Edwards, G., O’Neill, P.M., Ward, S.A., Winstanley, P.A., Mturi, N., Musumba, C.O., Wamola, B.M., Ogutu, B.R., Newton, C.R.: Cerebral malaria: optimising management. CNS Drugs 17, 153–165 (2003)

    Article  Google Scholar 

  27. Murthy, R. S. R., Majithiya, R. J., Ghosh P. K.: Thermoreversible-mucoadhesive gel for nasal delivery of Sumatriptan. AAPS PharmSciTech. 7(3), E1–E7 (2006). (http://www.aapspharmscitech.org)

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

    Article  CAS  Google Scholar 

  29. Ruel-Gariepy, E., Leroux, J.C.: In situ forming hydrogels—review of temperature- sensitive systems. Eur. J. Pharm. Biopharm. 58, 409–426 (2004)

    Article  CAS  Google Scholar 

  30. Shrivastava A., Nagori B.P., Saini P, Issarani R., Gaur S.S.: New simple and economical spectrophotometric method for estimation of artemether in pharmaceutical dosage forms. Asian J. Res. Chem. 1, 19–21 (2008)

    Google Scholar 

  31. Tu¨rker, S., Onur, E., O¨ zur, Y.: Nasal route and drug delivery systems. Pharm. World Sci. 26, 137–142 (2004)

    Article  Google Scholar 

  32. Uekama, K., Hirayama, F., Irie, T.: Cyclodextrin drug carrier systems. Chem. Rev. 98, 2045 (1998)

    Article  CAS  Google Scholar 

  33. Yong, C.S., Choi, J.S., Rhee, J.D.: Effect of sodium chloride on the gelation temperature, gel strength, and bioadhesive force of poloxamer gels containing diclofenac sodium. Int. J. Pharm. 226, 195–205 (2001)

    Article  CAS  Google Scholar 

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Acknowledgement

The authors are thankful to Macleod Pharmaceutical Ltd., Daman for generous gift of artemether drug sample.

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  1. R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India

    Hitendra S. Mahajan, Saurabh K. Shah & Sanjay J. Surana

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  1. Hitendra S. Mahajan
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Correspondence to Hitendra S. Mahajan.

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Mahajan, H.S., Shah, S.K. & Surana, S.J. Nasal in situ gel containing hydroxy propyl β-cyclodextrin inclusion complex of artemether: development and in vitro evaluation. J Incl Phenom Macrocycl Chem 70, 49–58 (2011). https://doi.org/10.1007/s10847-010-9861-x

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  • DOI: https://doi.org/10.1007/s10847-010-9861-x

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