Preparation of acrylic-type derivative of ibuprofen and in vitro evaluation studies of its polymeric prodrugs
الموضوعات : Journal of the Iranian Chemical ResearchMirzaagha Babazadeh 1 , Ladan Edjlali 2 , Zeynab Hajizeynalabedini 3
1 - Laboratory of Organic Chemistry, Applied Chemistry Department, Faculty of Sciences, Islamic Azad University, Tabriz Branch, Tabriz, Iran
2 - Laboratory of Organic Chemistry, Applied Chemistry Department, Faculty of Sciences, Islamic Azad University, Tabriz Branch, Tabriz, Iran
3 - Laboratory of Organic Chemistry, Applied Chemistry Department, Faculty of Sciences, Islamic Azad University, Tabriz Branch, Tabriz, Iran
الکلمات المفتاحية: Ibuprofen, Polymeric prodrug, Controlled release system, Polymerization,
ملخص المقالة :
Acrylic-type polymeric systems having degradable ester bonds linked to ibuprofen were synthesized and evaluated as materials for drug delivery. Ibuprofen, as a non-steroidal anti-inflammatory drug, was linked to 2-hydroxyethyl methacrylate by activated ester methodology in one-pot procedure. The resulting methacrylic derivative of ibuprofen was copolymerized with 2-hydroxyethyl methacrylate and n-butyl acrylate (in 1:3 mole ratio) by free radical polymerization method in N,N-dimethylformamide solution, utilizing azoisobutyronitrile as initiator at 65-70 oC. All of the obtained compounds were characterized by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis technique. The average molecular weights of the polymers bearing ibuprofen were determined by gel permeation chromatography and their polydispersity indices resulted in the range of 1.8-1.9. Release studies of ibuprofen were performed into dialysis bags by hydrolysis in buffered solutions (pH 1, 7.4 and 10) at 37 oC. Detection of hydrolysis by UV spectroscopy at selected intervals showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behaviour of polymeric prodrugs is strongly based on the polymer hydrophilicity and the pH value of the hydrolysis solution. The results suggest that these polymeric prodrugs could be useful for release of ibuprofen in controlled release systems.
[1] M. Chasin, R. Langer, Biodegradable Polymers as Drug Delivery Systems, Marcel Dekker, New York, 1990.
[2] R. Langer, D.L. Wise, Medical Application of Controlled Release, CRC Press, Boca Raton, Florida, 1984.
[3] B.D. Ratner, A.S. Hoffmann, F.J. Schoen, J.E. Lemons, An Introduction to Materials in Medicine, Academic Press, London, 1996.
[4] K. Hoste, K. Winne, E. Schacht, Int. J. Pharm. 277 (2004) 119.
[5] J. Khandare, T. Minko, Prog. Polym. Sci., 31 (2006) 359.
[6] M. Babazadeh, Int. J. Pharm. 356 (2008) 167.
[7] M. Babazadeh, J. Appl. Polym. Sci. 104 (2007) 2403.
[8] M. Babazadeh, L. Edjlali, L. Rashidian, J. Polym. Res. 14 (2007) 207.
[9] G. Giammona, G. Puglisi, B. Carlisi, R. Pignatello, A. Spadaro, A. Caruso, Int. J. Pharm. 57 (1989) 55.
[10] F.P. Bonina, L. Motenegro, P.D. Capraiis, F. Palagiano, G. Trapani, G. Liso, J. Controll. Release 34 (1995) 223.
[11] J. Caldwell, A.J. Hutt, S. Fournel-Gigleux, Biochem. Pharmacol. 37 (1988) 105.
[12] X. Cai, N. Wang, X. Lin, Polymer 47 (2006) 6491.
[13] C.H. Chang, Y.M. Sheu, W.P. Hu, L.F. Wang, J.S. Chen, J. Polym. Sci. Polym. Chem. 36 (1998) 1481.
[14] S. Davaran, A.A. Entezami, J. Bioact. Compact. Polym. 12 (1997) 47.
[15] S. Davaran, A.A. Entezami, J. Controll. Release 47 (1997), 41.
[16] S. Davaran, A.A. Entezami, Eur. Polym. J. 34 (1998) 187.
[17] M. Babazadeh, Int. J. Pharm. 316 (2006) 68.
[18] H.W. Kim, C.W. Chung, S.J. Hwang, Y.H. Rhee, Int. J. Biol. Macromol. 36 (2005) 84.
[19] S.Y. Kim, I.G. Shin, Y.M. Lee, C.S. Cho, Y.K. Sung, J. Controll. Release 51 (1998) 13.
[20] F.P. Bonina, C. Puglia, T. Barbuzzi, P.D. Caprariis, F. Palagiano, M.G. Rimoli, A. Saija, Eur. J. Pharm. Sci. 14 (2001) 123.
[21] M.H. Nasir Tablerizi, S. Davaran, A.A. Entezami, Iran. Polym. J. 5 (1996) 243.
[22] S. Davaran, J. Hanaee, A. Khosravi, J. Controll. Release 58 (1999) 297.
[23] C.L. Boudreaux, W.C. Bunyard, C.L. McCormic, J. Controll. Release 40 (1996) 223.
[24] J. Sanroman, B. Levenfeld, Macromolecules 23 (1990) 423.
[25] H. Namazi, M. Babazadeh, A. Sarabi, A. Entezami, J. Polym. Mater. 18 (2001) 301.
[26] C.S.J. Selvamalar, T. Krithiga, A. Penlidis, S. Nanjundan, React. Funct. Polym. 56 (2003) 89.
[27] B. Levenfeld, J. Sanroman, E.L. Madruga, Polymer 31 (1990) 160.
