Jump to ContentJump to Main Navigation

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

4 Issues per year

IMPACT FACTOR 2013: 1.025
5-year IMPACT FACTOR: 1.780

SCImago Journal Rank (SJR): 0.478
Source Normalized Impact per Paper (SNIP): 1.096

Open Access


Swelling behavior and release properties of pH-sensitive hydrogels based on methacrylic derivatives

Tahar Bartil1 / Mahmoud Bounekhel1 / Calberg Cedric1 / Robert Jeerome1

Département de génie des procédés Faculté des sciences de l'ingénieur, Université ferhat Abbas, SETIF (19000), Algérie1

Centre de recherche et d'étude sur les macromolécules (CERM) B6 chimie, Université de Liège Sart-Tilman, 4000-Liege, Belgique2

This content is open access.

Citation Information: Acta Pharmaceutica. Volume 57, Issue 3, Pages 301–314, ISSN (Online) 1846-9558, ISSN (Print) 1330-0075, DOI: 10.2478/v10007-007-0024-6, September 2007

Publication History

Published Online:

Swelling behavior and release properties of pH-sensitive hydrogels based on methacrylic derivatives

The purpose of this study is to develop novel intestinal-specific drug delivery systems with pH sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs were synthesized by free radical copolymerization of methacrylic acid, poly(ethyleneglycol monomethyl ether methacrylate) and a methacrylic derivative of N-(4-hydroxyphenyl)-2-(4-methoxyphenyl) acetamide in the presence of ethylene glycol dimethacrylate as crosslinking agent. The effect of copolymer composition on the swelling behavior and hydrolytic degradation were studied in simulated gastric (SGF, pH 1.2) and intestinal fluids (SIF, pH 7.0). The dynamic swelling behavior of these hydrogels was investigated to determine the mechanism of water transport through these hydrogels. The mechanism of water transport through the gels was significantly affected by the pH of the swelling medium and became more relaxation-controlled in a swelling medium of pH 7.0. The swelling and hydrolytic behaviors of hydrogels were dependent on the content of methacrylic acid (MAA) groups and caused a decrease and increase in gel swelling in SGF and SIF, respectively. Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. These results suggest that pH-sensitive systems could be useful for preparation of a muccoadhesive system and controlled release of N-(4-hydroxyphenyl)-2-(4-methoxyphenyl) acetamide.

Oslobađanje ljekovite tvari i bubrenje pH-senzitivnih hidrogelova na bazi metakrilnih derivata

Cilj rada bio je razviti nove pH senzitivne sustave za isporuku lijekova u tankom crijevu te ispitati njihova svojstva bubrenja i oslobađanje ljekovite tvari. Metakrilni polimerni prolijekovi sintetizirani su kopolimerizacijom derivata metakrilne kiseline sa slobodnim radikalima, poli(etilenglikol monometil eter metakrilata) i metakrilnog derivata N-(4-hidroksifenil)-2-(4-metoksifenil) acetamida u prisutnosti etilenglikol dimetakrilata kao sredstva za umrežavanje. Učinak sastava kopolimera na svojstvo bubrenja i hidrolitički raspad proučavan je u simuliranoj želučanoj (SGF, pH 1,2) i crijevnoj tekućini (SIF, pH 7,0). Dinamičko svojstvo bubrenja hidrogelova ispitivano je da bi se odredio mehanizam transporta vode kroz hidrogelove. Mehanizam prijenosa vode značajno je ovisio o pH medija. Bubrenje i hidrolitičko ponašanje hidrogelova ovisilo je o udjelu metakrilne kiseline. U SGF se bubrenje smanjivalo, a u SIF povećavalo. Povećanje udjela metakrilne kiseline u kopolimeru povećavalo je hidrolizu u SIF. Ti rezultati sugeriraju da se pH-senzitivni sustavi mogu upotrijebiti u pripravi mukoadhezivnih sustava i za kontrolirano oslobađanje N-(4-hidroksifenil)-2-(4-metoksifenil) acetamida.

Keywords: pH-sensitive hydrogels; swelling; controlled release; poly(ethylene glycol); poly(methacrylic acid)

Keywords: pH-senzitivni hidrogelovi; bubrenje; kontrolirano oslobađanje; poli(etilenglikol); poli-(metakrilna kiselina)

  • N. A. Peppas and W. Leobandung, Stimuli-sensitive hydrogels: ideal carriers for chronobiology and chronotherapy, J. Biomat. Sci. Polymer Ed.15 (2004) 125--144; DOI: 10.1163/156856204322793539. [CrossRef]

  • B. Lele and A. Hoffman, Bioadhesive properties of pegylated nanoparticles, J. Control. Rel.69 (2000) 237--248; DOI: 10.1016/S0168-3659(00)00303-5. [CrossRef]

  • A. Clausen and A. Bernkop-Schnürch, Direct compressible polymethacrylic acid-starch compositions for site specific drug delivery, J. Control. Rel.75 (2001) 93--102; DOI:10.1016/S0168-3659 (01)00366-2. [CrossRef]

  • M. Deshpande, M. Davies, M. Garnett, P. Williams, D. Armitage, L. Bailey, M. Vamvakaki, S. Armes and S. Stolnik, The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes, J. Control. Rel.97 (2004) 143--156; DOI:10.1016/j.jconrel. 2004.02.019. [CrossRef]

  • I. Porcar, P. Perrin and C. Tribet, UV-visible light: a novel route to tune the type of an emulsion, Langmuir17 (2001) 6905--6909. [CrossRef]

  • D. Solberg and L. Wegberg, Adsorption and flocculation behavior of cationic polyacrylamide and colloidal silica, Colloids Surf.A 219 (2003) 161--172.

  • G. Chitanu and A. Carpov, Ecologically benign polymers: The case of maleic polyelectrolytes, Environ. Sci. Technol.36 (2002) 1856--1860. [CrossRef]

  • A. Taubert, C. Kübel and D. Martin, Polymer induced microstructure variation in zinc oxide crystals precipitated from aqueous solution, J. Phys. Chem.B 107 (2003) 2660--2666; DOI: 10.1021/jp020569h S1089-5647(02)00569-2. [CrossRef]

  • A. M. Lowman, M. Morishita, M. Kajita, T. Nagai and N. A. Peppas, Oral delivery of insulin using pH-responsive complexation gels, J. Pharm. Sci.88 (1999) 933--937; DOI: 10.1021/js980337n. [CrossRef]

  • B. O. Haglund, R. J. Kenneth and J. Himmelstein, An in situ gelling system for parenteral delivery, J. Control. Rel.41 (1996) 229--235; DOI: 10.1016/0168-3659(96)01333-8. [CrossRef]

  • N. A. Peppas and A. R. Khare, Preparation, structure and diffusional behaviour of hydrogels in controlled release, Adv. Drug. Del. Rev.11 (1993) 1--35.

  • A. Gallardo and J. S. Roman, Synthesis and characterization of a new poly(methacrylamide) bearing side groups of biomedical interest, Polymer34 (1993) 394--400. [CrossRef]

  • H. E. Paulus and M. W. Whitehouse, Nonsteroid anti-inflammatory agents, Ann. Rev. Pharmacol. Toxicol.13 (1973) 107--125. [CrossRef]

  • R. Nickander, F. G. McMahon and A. S. Ridolfo, Nonsteroidal anti-inflammatory agents, Ann. Rev. Pharmacol. Toxicol.19 (1979) 469--490. [CrossRef]

  • S. S. Adams and J. W. Buckler, The Propionic Acids, in Antirheumatic Drugs (Ed. E. C. Huskisson), Praeger Scientific, Eastbourne 1983.

  • B. Kim and N. A. Peppas, Poly(ethylene glycol)-containing hydrogels for oral protein delivery applications, Biomed. Microdev.3 (2003) 333--341; DOI:10.1002/pts.766. [CrossRef]

  • United States Pharmacopeia 26/National Formulary 21, US Pharmacopeial Convention, Rockwille 1999, pp. 2130--2143.

  • B. Kim and N. A. Peppas, Synthesis and characterization of pH-sensitive glycopolymers for oral drug delivery systems, J. Biomater. Sci. Polym. Ed.13 (2002) 1271--1281; DOI: 10.1163/156856202320893000. [CrossRef]

  • M. Zerrari, Synthèse et Caractérisation des Systèmes de Libération à Base de Poly(ethylene glycol), Master Thesis, Ferhat Abbas University, Sétif Algeria, 2004.

  • S. Holappa, Complexation of Poly(ethylene Oxide)-Block-Poly(methacrylic acid) in Aqueous Medium, Dissertation, University of Helsinki, Helsinki 2005.

  • B. Kim and N. A. Peppas, Complexation phenomena in pH-responsive copolymer networks with pendent saccharides, Macromolecules35 (2002) 9545--9560. [CrossRef]

  • P. L. Rittger and N. A. Peppas, A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices, J. Control. Rel.5 (1987) 37--42; DOI: 10.1016/0168-3659(87)90035-6. [CrossRef]

  • A. R. Berens and H. B. Hopfenberg, Diffusion and relaxation in glassy polymer powders 2. Separation of diffusion and relaxation parameters, Polymer19 (1978) 489--496.

  • S. S. Shah, M. G. Kulkarni and R. A. Mashelkar, Release kinetics of pendant substituted bioactive molecules from swellable hydrogels: role of chemical reaction and diffusive transport, J. Membr. Sci.51 (1990) 83--95.

  • S. S. Shah, M. G. Kulkarni and R. Mashelkar, A mechanistic interpretation of the zero order release from pendant chain-linked glassy and swollen hydrogels, J. Appl. Polym. Sci.41 (1991) 2437--2451.

  • M. Torres-Lugo, M. Garc'a, R. Record and N. A. Peppas, Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanoparticles for oral delivery of proteins, J. Control. Rel.80 (2002) 197--208; DOI: 10.1016/S0168-3659(02)00027-5. [CrossRef]

  • C. G. Pitt, and S. S. Shah, The kinetics of drug cleavage and release from matrices containing covalent polymer-drug conjugates, J. Control Rel.33 (1995) 391--395; DOI: 10.1016/0168-3659 (94)00113-9 [CrossRef]

  • B. Kim and N. A. Peppas, Analysis of molecular interactions in P(MAA-g-EG) hydrogels, Polymer44 (2003) 3701--3707; DOI: 10.1016/S0032-3861(03)00307-0. [CrossRef]

Comments (0)

Please log in or register to comment.