Skip to main content
SpringerLink
Log in

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (Mc), polymer volume fraction in swollen state (V2s), number of repeating units between crosslinks (Mr) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Peppas NA, Mikos AG. Preparation methods and structure of hydrogels. In: Peppas NA, editor. Hydrogels in medicine and pharmacy fundamentals, vol. 1. Boca Raton, FL: CRC Press; 1986. p. 2–23.

    Google Scholar 

  2. Lin Y, Chen Q, Luo H. Preparation and characterization of N-(2-carboxybenzyl) chitosan as a potential pH-sensitive hydrogel for drug delivery. Carbohydr Res. 2007;342:87–95.

    Article  CAS  PubMed  Google Scholar 

  3. Mudassir J, Ranjha NM. Dynamic and equilibrium swelling studies: crosslinked pH sensitive methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels. J Polym Res. 2008;15:195–203.

    Article  CAS  Google Scholar 

  4. Zhang J, Chu LY, Li YK, Lee YM. Dual thermo- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors. Polymer. 2007;48:1718–28.

    Article  CAS  Google Scholar 

  5. Elliotta JE, Macdonada M, Niea J, Bowman CN. Structure and swelling of poly(acrylic acid) hydrogels: effect of pH, ionic strength and dilution on the cross-linked polymer structure. Polymer. 2004;45:1503–10.

    Article  Google Scholar 

  6. Ranjha NM, Mudassir J, Akhtar N. Methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels for controlled drug delivery. J Sol-Gel Sci Technol. 2008;47:23–30.

    Article  CAS  Google Scholar 

  7. Seigel RA. Hydrophobic weak polyelectrolyte gels-studies of swelling equilibria and kinetics. Adv Polym Sci. 1993;5:233–42.

    Google Scholar 

  8. Huang Y, Yu H, Xiao C. pH-sensitive cationic guargum/poly(acrylic acid) polyelectrolyte hydrogels: swelling and in vitro drug release. Carbohydr Polym. 2007;69:774–83.

    Article  CAS  Google Scholar 

  9. Fournier F, Passirani C, Montero-Menci CN, Benoit JP. Biocompatibility of implantable synthetic polymeric drug carriers: focus on brain compatibility. Biomaterials. 2003;24:3311–31.

    Article  CAS  PubMed  Google Scholar 

  10. Park H, Robinson JR. Mechanisms of mucoadhesion of poly(acrylic acid) hydrogels. Pharm Res. 1987;4:457–64.

    Article  CAS  PubMed  Google Scholar 

  11. Yan X, Gemeinhart RA. Cisplatin delivery from poly(acrylic acid-co-methyl methacrylate) microparticles. J Control Rel. 2005;106:198–208.

    Article  CAS  Google Scholar 

  12. Risbud MV, Bhonde RR. Polyacrylamide-chitosan hydrogels: in vitro biocompatibilty and sustained antibiotic release studies. Drug Deliv. 2000;7:69–75.

    Article  CAS  PubMed  Google Scholar 

  13. Kim IS, Oh IJ. Drug release from the enzyme-degradable and pH-sensitive hydrogel composed of glycidyl methacrylate dextran and poly(acrylic acid). Arch Pharmacal Res. 2005;28:983–7.

    Article  CAS  Google Scholar 

  14. Liu ZL, Hu H, Zhuo RX. Konjac glucomannan-graft acrylic acid hydrogels containing azo crosslinker for colon-specific delivery. J Polym Sci Part A. 2004;42:4370–8.

    Article  CAS  Google Scholar 

  15. George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Release. 2006;114:1–14.

    Article  CAS  PubMed  Google Scholar 

  16. Yao KD, Peng T, Feng HB, He YY. Swelling kinetics and release characteristic of crosslinked chitosan–polyether polymer network (semi-IPN) hydrogels. J Polym Sci A. 1994;32:1213–23.

    Article  CAS  Google Scholar 

  17. Torrado S, Prada P, de la Torre PM, Torrado S. Chitosan-poly(acrylic) acid polyionic complex: in vivo study to demonstrate prolonged gastric retention. Biomaterials. 2004;25:917–23.

    Article  CAS  PubMed  Google Scholar 

  18. Ranjha NM. Synthesis and characterization of non-crosslinked and crosslinked poly(vinyl alcohol-co-crotonic acid) hydrogels. Saudi Pharm J. 1999;7:130–6.

    CAS  Google Scholar 

  19. Li X, Wu W, Wang J, Duan Y. The swelling behavior and network parameters of guar gum/poly(acrylic acid) semi-interpenetrating polymer network hydrogels. Carbohydr Polym. 2006;66:473–9.

    Article  CAS  Google Scholar 

  20. Peppas NA, Barr-Howel BD. Characterization of the crosslinked structure of hydrogels. In: Peppas NA, editor. Hydrogels in: medicine and pharmacy fundamentals, vol. 1. Boca Raton, FL: CRC Press; 1987. p. 22–56.

    Google Scholar 

  21. Crank J. The mathematics of diffusion. 2nd ed. Oxford: Claredon press; 1975. p. 244.

    Google Scholar 

  22. Flory PJ. Principles of polymer chemistry. Ithaca, NY: Cornell University; 1953.

    Google Scholar 

  23. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J (2000) Physicochemical, foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng; pp 9–29.

  24. Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000;50:27–46.

    Article  CAS  PubMed  Google Scholar 

  25. Alla SGA, El-Din HMN, El-Naggar AWM. Structure and swelling-release behaviour of poly(vinyl pyrrolidone) (PVP) and acrylic acid (AAc) copolymer hydrogels prepared by gamma irradiation. Eur Polym J. 2007;43:2987–98.

    Article  Google Scholar 

  26. Yin L, Fei L, Cui F, Tang C, Yin C. Superporous hydrogels containing poly(acrylicacid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials. 2007;28:1258–66.

    Article  CAS  PubMed  Google Scholar 

  27. Najib N, Suleiman M. The kinetics of drug release from ethyl cellulose solid dispersions. Drug Dev Ind Pharm. 1985;11:2169–89.

    Article  CAS  Google Scholar 

  28. Desai SJ, Singh P, Simonelli AP, Higuchi WI. Investigation of factors influencing release of solid drug dispersed in wax matices. Quantitative studies involving polyethylene plastic matrix. J Pharm Sci. 1966;55:1230–4.

    Article  CAS  PubMed  Google Scholar 

  29. Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;50:1145–9.

    Article  Google Scholar 

  30. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.

    CAS  PubMed  Google Scholar 

  31. Lin Y, Chen Q, Luo H. Preparation and characterization of N-(2-carboxybenzyl) chitosan as a potential pH-sensitive hydrogel for drug delivery. Carbohydr Res. 2007;342:87–95.

    Article  CAS  PubMed  Google Scholar 

  32. Ranjha NM, Doelker E. pH-sensitive non-crosslinked poly(vinyl alcohol-co-acrylic acid) hydrogels for site specific drug delivery. Saudi Pharm J. 1999;7:137–43.

    CAS  Google Scholar 

  33. Praday M, Kopecek J. poly[(acrylic acid)-co-(butyl acetate)] crosslinked with 4,4-bis (methacryloylamino) azobenzene. Makromol Chem. 1990;191:1887–97.

    Article  Google Scholar 

  34. Dergunova SA, Namb IK, Muna GA, Nurkeevaa Z, Shaikhutdinov EM. Radiation synthesis and characterization of stimuli-sensitive chitosan–polyvinyl pyrrolidone hydrogels. Radiat Phys chem. 2005;72:619–23.

    Article  ADS  Google Scholar 

  35. Yin L, Fei L, Cui F, Tang C, Yin C. Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials. 2007;28:1258–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, B.Z. University, Multan, Pakistan

    Nazar M. Ranjha & Muhammad Tayyab Ansari

  2. Drug Testing Laboratory, Multan, Pakistan

    Gohar Ayub

  3. Centre of Excellence in Solid State Physics, Punjab University, Lahore, Pakistan

    Shahzad Naseem

Authors
  1. Nazar M. Ranjha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gohar Ayub
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shahzad Naseem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Tayyab Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nazar M. Ranjha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ranjha, N.M., Ayub, G., Naseem, S. et al. Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil. J Mater Sci: Mater Med 21, 2805–2816 (2010). https://doi.org/10.1007/s10856-010-4134-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-010-4134-1

Keywords

Search

Navigation