Journal of Materials Science: Materials in Medicine

, Volume 21, Issue 12, pp 3129–3140 | Cite as

An in vitro release study of indomethacin from nanoparticles based on methyl methacrylate/glycidyl methacrylate copolymers



Indomethacin was coupled onto some macromolecular nanostructures based on methyl methacrylate copolymers with glycidyl methacrylate and tested as a model drug. The polymeric matrices were synthesized by radical emulsion copolymerization with and without the presence of a continuous external magnetic field of 1500 Gs intensity. Mathematical analysis of the release data was performed using Higuchi, Peppas–Korsmeyer equations. NIR chemical imaging (NIR-CI) was used to provide information about the spatial distribution of the components in the studied nanostructures. This opportunity was used to visualize the spatial distribution of bioactive substances (indomethacin) into the polymeric matrix, as well as to evaluate the degree of chemical and/or physical heterogeneity of the bioactive samples. The release rate dependence on the synthesis conditions as well as on the chemical compositions of the tested polymeric systems, it was also evidenced.


Drug Release Indomethacin Partial Little Square Polymeric Matrice Sodium Lauryl Sulphate 



The authors thank to Prof. Clara Silvestre and Prof. Sossio Cimmino (CNR-Istituto di Chimica e Tecnologia dei Polimeri—Naples Italy) for their support and their many and helpful suggestions regarding SEM microscopy. This research was financially suported by European Social Fund—“Cristofor I. Simionescu” Postdoctoral Fellowship Programme (IDPOSDRU/89/1.5/S/55216), Sectoral Operational Programme Human Resources Development 2007–2013.


  1. 1.
    Bravo-Osuna I, Ferrero C, Jimenez-Castellanos MR. Drug release behaviour from methyl methacrylate-starch matrix tablets: effect of polymer moisture content. Eur J Pharma Biopharma. 2008;69:285–93.CrossRefGoogle Scholar
  2. 2.
    Chretien C, Boudy V, Allain P, Chaumeil JC. Indomethacin release from ion-exchange microspheres: impregnation with alginate reduces release rate. J Cont Rel. 2004;96:369–78.CrossRefGoogle Scholar
  3. 3.
    Albin P, Markus A, Pelah Z, Ben-Zvi Z. Slow-release indomethacin formulations based on polysaccharides: evaluation in vitro and in vivo in dogs. J Cont Rel. 1994;29:25–39.CrossRefGoogle Scholar
  4. 4.
    Ferreira Almeida P, Almeida AJ. Cross-linked alginate–gelatine beads: a new matrix for controlled release of pindolol. J Cont Rel. 2004;97:431–9.Google Scholar
  5. 5.
    Satoh T, Higuchi Y, Kawakami S, Hashida M, Kagechika H, Shudo Ki, Yokoyama M. Encapsulation of the synthetic retinoids Am80 and LE540 into polymeric micelles and the retinoids’ release control. J Cont Rel. 2009;136:187–95.CrossRefGoogle Scholar
  6. 6.
    Khandare J, Minko T. Polymer–drug conjugates: progress in polymeric prodrugs. Prog Polym Sci. 2006;31:359–97.CrossRefGoogle Scholar
  7. 7.
    Changerath R, Nair PD, Mathew S, Nair CP. Poly(methyl methacrylate)-grafted chitosan microspheres for controlled release of ampicillin. J Biomed Mater Res B Appl Biomater. 2009;89:65–76.PubMedGoogle Scholar
  8. 8.
    Ferrero C, Bravo I, Jimenez-Castellanos MR. Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets: effect of copolymer type and matrix porosity. J Cont Rel. 2003;92:69–82.CrossRefGoogle Scholar
  9. 9.
    Castellano I, Gurruchaga M, Goni I. The influence of drying method on the physical properties of some graft copolymers for drug delivery systems. Carbohydr Polym. 1997;34:83–9.CrossRefGoogle Scholar
  10. 10.
    Ferrero C, Jime′nez-Castellanos MR. The influence of carbohydrate nature and drying methods on the compaction properties and pore structure of new methyl methacrylate copolymers. Int J Pharm. 2002;248:157–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Ferrero C, Bravo I, Jimenez-Castellanos MR. Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets: effect of copolymer type and matrix porosity. J Control Rel. 2003;92:69–82.CrossRefGoogle Scholar
  12. 12.
    Bravo-Osuna I, Ferrero C, Jimenez-Castellanos MR. Water sorption–desorption behaviour of methyl methacrylate–starch copolymers: effect of hydrophobic graft and drying method. Eur J Pharm Biopharm. 2005;59:537–48.CrossRefPubMedGoogle Scholar
  13. 13.
    Sairam M, Ramesh Babu V, Krishna Rao KSV, Aminabhavi TM. Poly(methylmethacrylate)-poly(vinyl pyrrolidone) microspheres as drug delivery systems: indomethacin/cefadroxil loading and in vitro release study. J Appl Polym Sci. 2007;104:1860–5.CrossRefGoogle Scholar
  14. 14.
    Elizalde-Peña EA, Flores-Ramirez N, Luna-Barcenas G, Vásquez-García SR, Arámbula-Villa G, García-Gaitán B, Rutiaga-Quiñones JG, González-Hernández J. Synthesis and characterization of chitosan-g-glycidyl methacrylate with methyl methacrylate. Eur Polym J. 2007;43:3963–9.CrossRefGoogle Scholar
  15. 15.
    Salikhov KM, Molin YuN, Sagdeev RZ, Buchachenko AL. Spin polarization and magnetic effects in radical reactions. Amsterdam: Elsevier Press; 1984.Google Scholar
  16. 16.
    Khudyakov IV, Serebrennikov YuA, Turro NJ. Spin-orbit coupling in free-radical reactions: on the way to heavy elements. Chem Rev. 1993;93:537.CrossRefGoogle Scholar
  17. 17.
    Steiner UE, Ulrich T. Magnetic field effects in chemical kinetics and related phenomena. Chem Rev. 1989;89:51.CrossRefGoogle Scholar
  18. 18.
    Steiner UE, Wolff HJ. Photochemistry and photophysics. Boca Raton, Boston: CRC Press; 1991.Google Scholar
  19. 19.
    Chiriac AP. Polymerization in a magnetic field. 14. Possibilities to improve field effect during methyl acrylate polymerization. J Appl Polym Sci. 2004;92(2):1031–6.CrossRefMathSciNetGoogle Scholar
  20. 20.
    Simionescu CI, Chiriac AP, Chiriac MV. Polymerization in a magnetic field: 1. Influence of esteric chain length on the synthesis of various poly(methacrylate)s. Polymer. 1993;18:3917–20.CrossRefGoogle Scholar
  21. 21.
    Simionescu CI, Chiriac AP. Influence of a magnetic field on radicalic polymerization of butyl methacrylate. Coll Polym Sci. 1992;270:753–8.CrossRefGoogle Scholar
  22. 22.
    Chiriac AP, Simionescu CI. Polymerization in a magnetic field. X. Solvent effect in poly(methyl methacrylate) synthesis. J Pol Sci: A: Polym Chem. 1996;34:567–73.CrossRefGoogle Scholar
  23. 23.
    Chiriac AP. Polymerization in magnetic field. XVI. Kinetic aspects regarding methyl methacrylate polymerization in high magnetic field. J Polym Sci A. 2004;42(22):5678–86.CrossRefGoogle Scholar
  24. 24.
    Chiriac AP, Simionescu CI. Polymerization in a magnetic field. Prog Polym Sci. 2000;25(2):219–58.CrossRefGoogle Scholar
  25. 25.
    Chiriac AP. Polymerization in a magnetic field. XV Some azo-initiators behavior in a high magnetic field. J Appl Polym Sci. 2004;98(3):1025–31.CrossRefGoogle Scholar
  26. 26.
    Nita LE, Chiriac AP. Polymerization in a magnetic field, part 17: styrene copolymerization with 2,3-epoxypropyl methacrylate. J Appl Polym Sci. 2007;104(5):3029–35.CrossRefGoogle Scholar
  27. 27.
    Nita LE, Chiriac AP, Cimmino S, Silvestre C, Duraccio D, Vasile C. Polymerization in magnetic field. XIX. Thermal behavior of the copolymers of methyl methacrylate with glycidyl methacrylate synthesized in the magnetic field presence. Open Macromol J. 2008;2:26–31.CrossRefGoogle Scholar
  28. 28.
    Nita LE, Chiriac AP. Effect of emulsion polymerization and magnetic field on the adsorption of albumin on poly(methyl methacrylate)-based biomaterial surfaces. J Mater Sci: Mater Med. 2010;21(8):2443–52.CrossRefGoogle Scholar
  29. 29.
    Nita LE, Chiriac AP, Cimmino S, Silvestre C, Duraccio D, Vasile C. Polymerization in magnetic field: XVIII. Influence of surfactant nature on the synthesis and thermal properties of poly(methyl methacrylate) and poly[(methyl methacrylate)-co-(epoxypropyl methacrylate)]. Polym Int. 2008;57:342–9.CrossRefGoogle Scholar
  30. 30.
    Li J, Jun Loh X. Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv Drug Deliv Rev. 2008;60:1000–17.CrossRefPubMedGoogle Scholar
  31. 31.
    Rayn C, Skibsted E, Bro R. Near-infrared chemical imagining (NIR-CI) on pharmaceutical solid dosage forms. J Pharm Biomed Anal. 2008;48:554–61.CrossRefGoogle Scholar
  32. 32.
    Reich G. Near-infrared spectroscopy and imaging: basic principles and pharmaceutical application. Adv Drug Deliv Rev. 2005;57:1109–43.CrossRefPubMedGoogle Scholar
  33. 33.
    Reich G. Use of DSC and NIR spectroscopy to study the hydration, degradation and drug release behavior of PLA/PLGA microparticles and films with free and blocked carboxylic end groups. Proc Int Symp Control Release Bioact Mater. 2000;27:642–3.Google Scholar
  34. 34.
    Gendrin C, Roggo Y, Collet C. Direct quantification and distribution assessment of major and minor components in pharmaceutical tablets by NIR-chemical imaging. Talanta. 2007;73:733–41.CrossRefPubMedGoogle Scholar
  35. 35.
    Ciurczak EW, Drennen JK III, editors. Pharmaceutical and medical applications of near-infrared spectroscopy. New York: Marcel Dekker Inc; 2002.Google Scholar
  36. 36.
    Jovanovic N, Gerich A, Bouchard A, Jiskoot W. Near-infrared imaging for studying homogeneity of protein-sugar mixtures. Pharm Res. 2006;23:2002–13.CrossRefPubMedGoogle Scholar
  37. 37.
    Furukawa T, Sato H, Shinzawa H, Noda I, Ochiai S. Evaluation of homogeneity of binary blends of poly(3-hydroxybutyrate) and poly(l-lactic acid) studied by near infrared chemical imaging (NIRCI). Anal Sci. 2007;23:871–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Nita LE, Chiriac AP, Neamtu I, Bercea M, Pintilie M. An analysis of the complexation between poly(aspartic acid) and poly(ethylene glycol). Colloids Surf A: Physicochem Eng Asp. 2009;348(1–3):254–62.CrossRefGoogle Scholar
  39. 39.
    Coutts-Lendon CA, Wrightb NA, Miesob EV, Koenig JL. The use of FT-IR imaging as an analytical tool for the characterization of drug delivery systems. J Control Rel. 2003;93:223–48.CrossRefGoogle Scholar
  40. 40.
    Rosman TJ, Higuchi WI. Release of medroxyprogesterone acetate from a silicone polymer. J Pharm Sci. 1970;59:353–7.CrossRefGoogle Scholar
  41. 41.
    Otsuka M, Nakahigashi Y, Matsuda Y, Fox JL, Higuchi WI, Sugiyama YA. Novel skeletal drug delivery system using self-setting calcium phosphate cement VIII: the relationship between in vitro and in vivo drug release from indomethacin-containing cement. J Cont Rel. 1997;43:115–22.CrossRefGoogle Scholar
  42. 42.
    Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35.CrossRefGoogle Scholar
  43. 43.
    Ritger PL, Peppas NA. A simple equation for description of solute release II. Fiction and anomalous release from swellable devices. J Cont Rel. 1987;5:37–42.CrossRefGoogle Scholar
  44. 44.
    Kocova SA, Leuenberger H. Modelling of drug release from polymer matrices: effect of drug loading. Int J Pharm. 1995;121:141–8.CrossRefGoogle Scholar
  45. 45.
    Carli F, Capone G, Colombo I, Magarotto L, Motta A. Surface and transport properties of acrylic polymers influencing drug release from porous matrices. Int J Pharm. 1984;21:317–29.CrossRefGoogle Scholar
  46. 46.
    Colombo P, Conte U, Caramella C, Gazzaniga A, La Manna A. Compressed polymeric mini-matrices for drug release control. J Control Rel. 1985;1:283–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.“Petru Poni” Institute of Macromolecular ChemistryIasiRomania

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