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Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels

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Abstract

In the present work, a series of cross-linked LVCS/PVA hydrogels with various feed compositions were prepared using glutaraldehyde as cross-linking agent. The prepared hydrogels were used for dynamic and equilibrium swelling studies. The swelling behavior of these hydrogels was investigated as functions of effect of pH, polymeric compositions and degree of cross-linking. Swelling studies were performed in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing PVA contents in the structure of hydrogels in solutions of higher pH values. This is due to the presence of more hydroxyl groups (–OH) in the PVA structure. On the other hand, by increasing LVCS contents, swelling increased in a solution of acidic pH and it is due to ionization of amino groups (–NH2), but this swelling was not significant. Swelling of hydrogels was decreased with increase in cross-linking ratio due to tighter hydrogel structure. Porosity and sol–gel fraction were also investigated. It was found that with increase in LVCS and PVA contents porosity and gel fraction increased, whereas by increasing glutaraldehyde content gel fraction increased and porosity decreased. Diffusion coefficient (D) and network parameters, i.e., the average molecular weight between cross-links (M C), solvent interaction parameters (χ), polymer volume fraction in swollen state (V 2S) and cross-linked density (q) were calculated using Flory–Rehner theory. Selected samples were loaded with model drug diphenhydramine HCl. The release of diphenhydramine HCl was studied for 12 h period in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5 and 7.5. It was observed that drug release increased with increasing PVA contents in the hydrogels, while release of drug decreased as the ratio of cross-linking agent increased in the hydrogel structure owing to strong physical entanglements between polymers. The release mechanisms were studied by fitting experimental data to model equations like zero order, first order, Higuchi and Peppas. Results showed that the kinetics of drug release from hydrogels in buffer solutions of pH 1.2, 5.5 and 7.5 was mainly non-fickian diffusion. Hydrogels were characterized by Fourier transform infrared and X-ray diffraction to confirm the structure and study the crystallinity of hydrogel, respectively.

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References

  1. Rodigues IR, Forte MMC, Azambuja DS, Castagno KRL (2007) Synthesis and characterization of hybrid polymeric networks (HPN) based on poly (vinyl alcohol)/chitosan. React Funct Polym 67:708–715

    Article  Google Scholar 

  2. Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Del Rev 60:1638–1649

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Pourjavadia, Mahdavnia GR (2006) Superabsorbency, pH-sensitivity and swelling kinetics of partially hydrolyzed chitosan-g-poly(acrylamide) hydrogels. Turk J Chem 30:595–608

    Google Scholar 

  5. Devine MD, Devery MS, Lyons GJ, Geever ML, Keenedy EJ, Higginbotham LC (2006) Multifunctional polyvinylpyrrolidinone-polyacrylic acid copolymer hydrogels for biomedical applications. Int J Pharm 326:50–59

    Article  CAS  Google Scholar 

  6. Peppas NA, Hilt ZJ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360

    Article  CAS  Google Scholar 

  7. Ranjha NM, Ayub G, Naseem S, Ansari MT (2010) 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

    Article  CAS  Google Scholar 

  8. Fodor CS, Domjan A, Ivan B (2013) Unprecedented scissor effect of macromolecular cross-linkers on the glass transition temperature of poly(N-vinylimidazole), crystallinity suppression of poly(tetrahydrofuran) and molecular mobility by solid state NMR in poly(N-vinylimidazole)-l-poly(tetrahydrofuran) conetworks. Polym Chem 4:3714–3724

    Article  CAS  Google Scholar 

  9. Kali G, Georgiou TK, Ivan B, Patrickios CS, Loizou E, Thomann Y, Tiller JC (2007) Synthesis and characterization of anionic amphiphilic model conetworks based on methacrylic acid and methyl methacrylate: effects of composition and architecture. Macromolecules 40:2192–2200

    Article  CAS  Google Scholar 

  10. Singh A, Narvi SS, Dutta PK, Pandy ND (2006) External stimuli response on a novel chitosan hydrogel crosslinked with formaldehyde. Ind Acad Sci 29(3):233–238

    CAS  Google Scholar 

  11. Ivan B, Haraszti M, Erdodi G, Scherble J, Thomann R, Mulhaupt R (2005) New nanophase separated intelligent amphiphilic conetworks and gels. Macromol Symp 227:265–273

    Article  CAS  Google Scholar 

  12. Bruns N, Scherble J, Hartmann L, Thomann R, Ivan B, Mulhaupt R, Tiller JC (2005) Nanophase separated amphiphilic conetwork coatings and membranes. Macromolecules 38:2431–2438

    Article  CAS  Google Scholar 

  13. Cascone MG, Barbani N, Cristallini C, Giusti P, Ciardelli G, Lazzeri L (2001) Bioartificial polymeric materials based on polysaccharides. J Biomater Sci Polym Edn 12(3):267–281

    Article  CAS  Google Scholar 

  14. Kim IS, Oh IJ (2005) Drug release from the enzyme-degradable and pH- sensitive hydrogel composed of glycidyl methacrylate dextran and poly(acrylic acid). Arch Pharmacal Res 28:983–987

    Article  CAS  Google Scholar 

  15. Scherble J, Thomann R, Ivan B, Mulhaupt R (2001) Formation of CdS nanoclusters in phase-separated poly(2-hydroxyethylmethacrylate)-l-polyisobutylene amphiphilic conetworks. J Polym Sci Part B Polym Phys 39:1429–1436

    Article  CAS  Google Scholar 

  16. Liu ZL, Hu H, Zhuo RX (2004) Konjac glucomannan-graft acrylic acid hydrogels containing azo crosslinker for colon-specific delivery. J Polym Sci Part A 42:4370–4378

    Article  CAS  Google Scholar 

  17. Abdeen Z (2011) Swelling and reswelling characteristics of cross-linked poly(vinyl alcohol)/chitosan hydrogel film. J Dispers Sci Technol 32:1337–1344

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Yao KD, Peng T, Feng HB, He YY (1994) Swelling kinetics and release characteristics of crosslinked chitosan-polyether polymer network (semi-IPN) hydrogels. J Polym Sci A 32:1213–1223

    Article  CAS  Google Scholar 

  20. Hassan CM, Peppas NA (2000) Cellular PVA hydrogels produced by freeze/thawing. J Appl Polym Sci 76:2075–2079

    Article  CAS  Google Scholar 

  21. Basak P, Adhikari B, Sen AK (2011) Surface crosslinked poly(vinyl alcohol) hydrogel for colon targeted drug release. Polym Plast Technol Eng 50:1357–1361

    Article  CAS  Google Scholar 

  22. More SM, Kulkarni RV, Sa B, Kayane NV (2010) Glutaraldehyde crosslinked poly(vinyl alcohol) hydrogel discs for the controlled release of antidiabetic drug. J Appl Polym Sci 116:1732–1738

    CAS  Google Scholar 

  23. Agostini JV, Leo-Summers LS, Inouye SK (2001) Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Int Med 161(17):2091–2097

    Article  CAS  Google Scholar 

  24. Edebi VN, Ebeshi BU, Anganabiri E (2011) Simultaneous assay of codeine phosphate and diphenhydramine hydrochloride in cough mixtures by zero-order derivative UV spectrophotometry. Afr J Pure Appl Chem 5(5):104–110

    CAS  Google Scholar 

  25. Guanghua HE, Hua Z, Fuliang X (2008) Preparation and swelling behavior of physically crosslinked hydrogels composed of poly(vinyl alcohol) and chitosan. J Wuhan Uni Technol Mate 23(6):816–820

    Article  Google Scholar 

  26. Denkbas EB, Kilicay E, Birlikseven C, Ozturk E (2002) Magnetic chitosan microspheres: preparation and characterization. React Funct Polym 50:225–232

    Article  CAS  Google Scholar 

  27. Zhang J, Chu LY, Cheng CJ, Mi DF, Zhou MY, Ju XJ (2008) Graft-type poly (N- isopropylacrylamide-co-acrylic acid) microgels exhibiting rapid thermo- and pH-responsive properties. Polymer 49:2595–2603

    Article  CAS  Google Scholar 

  28. Ranjha NM, Mudassir J, Sheikh ZZ (2011) Synthesis and characterization of pH-sensitive pectin/acrylic acid hydrogels for verapamil release study. Iran Polym J 20(2):147–159

    CAS  Google Scholar 

  29. Solpan D, Duran S, Saraydin D, Guven O (2003) Adsorption of methyl violet in aqueous solutions by poly(acrylamide-co-acrylic acid) hydrogels. Radiat Phys Chem 66:117–127

    Article  CAS  Google Scholar 

  30. Crank J (1975) In the mathematics of diffusion, 2nd edn. Clerendon Press, Oxford 244

    Google Scholar 

  31. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J (2000) Physicochemical foundations and structural design of hydrogels in medicine and biology. Annul Rev Biomed Eng 2:9–29

    Article  CAS  Google Scholar 

  32. Erdodi G, Ivan B (2004) Novel amphiphilic conetworks composed of telechelic poly(ethylene oxide) and three-arm star polyisobutylene. Chem Mater 16:959–962

    Article  Google Scholar 

  33. Haraszti M, Toth E, Ivan B (2006) Poly(methacrylic acid)-l-polyisobutylene: a novel polyelectrolyte amphiphilic conetwork. Chem Mater 18:4952–4958

    Article  CAS  Google Scholar 

  34. Georgiou TK, Groh PW, Ivan B, Patrickios CS (2007) Amphiphilic model conetworks of polyisobutylene methacrylate and 2- (dimethylamino)ethyl methacrylate prepared by the combination of quasiliving carbocationic and group transfer polymerizations. Macromolecules 40:2335–2343

    Article  CAS  Google Scholar 

  35. Winkelhausen E, Jovanovic-Malinovska R, Kuzmanova S, Cvetkovska M, Tsvetanov C (2008) Hydrogels based on u.v.-crosslinked poly(ethylene oxide)—matrices for immobilization of Candida boidinii cells for xylitol production. World J Microbiol Biotechnol 24:2035–2043

    Article  CAS  Google Scholar 

  36. Ivan B, Almdal K, Mortensen K, Johannsen I, Kops J (2001) Synthesis, characterization, and structural investigations of poly(ethyl acrylate)-l-polyisobutylene bicomponent conetwork. Macromolecules 34:1579–1585

    Article  CAS  Google Scholar 

  37. Domjan A, Erdodi G, Wilhelm M, Neidhöfer M, Landfester K, Ivan B, Spiess HW (2003) Structural studies of nanophase-separated poly(2-hydroxyethyl methacrylate)-l-polyisobutylene amphiphilic conetworks by solid-state NMR and small-angle X-ray scattering. Macromolecules 36:9107–9114

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  39. Alla SGA, El-din HMN, El-Naggar AWM (2007) Structure and swelling-release behaviour of poly(vinyl pyrrolidone) (PVP) and acrylic acid (AAc) copolymer hydrogels prepared by gamma irradiation. J Eur Polym 43:2987–2998

    Article  Google Scholar 

  40. Yin L, Fei L, Cui F, Tang C, Yin C (2007) Superporous hydrogels containing poly(acrylicacid-co-acrylamide)/O-carboxymethylchitosan interpenetrating polymer networks. Biomaterials 28:1258–1266

    Article  CAS  Google Scholar 

  41. Chen S, Liu M, Jin S, Wang B (2008) Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors. Int J Pharm 349:180–187

    Article  CAS  Google Scholar 

  42. Siemoneit U, Schmitt C, Lorenzo CA, Luazardo A, Espinar FO, Concheiro A, Mendaez J (2006) Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capatability. Int J Pharm 312:66–74

    Article  CAS  Google Scholar 

  43. Rao KSVK, Naidu BVK, Subha MCS, Sairam M, Aminabhavi TM (2006) Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil. Carbohydr Polym 66:333–344

    Article  CAS  Google Scholar 

  44. Serraa L, Nechc JD, Peppas NA (2006) Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels. Biomaterials 27:5440–5451

    Article  Google Scholar 

  45. Najib N, Suleiman M (1985) The kinetics of drug release from ethyl cellulose solid dispersions. Drug Dev Ind Pharm 11:2169–2189

    Article  CAS  Google Scholar 

  46. Higuchi T (1963) Mechanism of sustained action medication. Theoretical analysis of rate of release of solid drugs dispersed in sold matrices. J Pharm Sci 50:1145–1149

    Article  Google Scholar 

  47. Li S, Shen Y, Li W, Hao X (2006) A Common profile for polymer-based controlled release and its logical interpretation to general release process. J Pharm Sci 9(2):238–244

    CAS  Google Scholar 

  48. Ahn JS, Choi HK, Chun MK, Ryu JM, Jung JH, Kim YU, Cho CS (2002) Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro. Biomaterials 23:1411–1416

    Article  CAS  Google Scholar 

  49. Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA (1983) Mechanism of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35

    Article  CAS  Google Scholar 

  50. Kim SJ, Lee KJ, Kim IY, Kim SI (2003) Swelling kinetics of interpenetrating polymer hydrogels composed of poly(vinyl alcohol)/chitosan. J macromol sci A40(5):501–510

    Article  CAS  Google Scholar 

  51. Bahrami SB, Kordestani SS, Mirzadeh H, Mansoori P (2003) Poly(vinyl alcohol)—chitosan blends: preparation, mechanical and physical properties. Iran Polym J 12(2):139–146

    CAS  Google Scholar 

  52. Sung JH, Hwang MR, Kim JO, Lee JH, Kim YI, Kim JH, Chang SW, Jin SG, Kim JA, Lyoo WS, Han SS, Ku SK, Yong SH, Choi HG (2010) Gel characterization and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using poly(vinyl alcohol) and chitosan. Int J Pharm 392:232–240

    Article  CAS  Google Scholar 

  53. Liu J, Wang W, Wang A (2011) Synthesis, characterization, and swelling behaviors of chitosan-g-poly(acrylic acid)/poly(vinyl alcohol) semi-IPN superabsorbent hydrogels. Polym Adv Technol 22:627–634

    Article  CAS  Google Scholar 

  54. Shukla S, Bajpai AK, Kulkarni RA (2005) Preparation, characterization, and water-sorption study of poly(vinyl alcohol) based hydrogels with grafted hydrophilic and hydrophobic segments. J Appl Polym Sci 95:1129–1142

    Article  CAS  Google Scholar 

  55. Kali G, Georgiou TK, Ivan B, Patrickios CS, Loizou E, Thomann Y, Tiller JC (2007) Synthesis and characterization of anionic amphiphilic model conetworks of 2- butyl-1-octyl-methacrylate and methacrylic acid: effects of polymer composition and architecture. Langmuir 23:10746–10755

    Article  CAS  Google Scholar 

  56. Fodor CS, Kali G, Ivan B (2011) Poly(N-vinylimidazole)-l-poly(tetrahydrofuran) amphiphilic conetworks and gels: synthesis, characterization, thermal and swelling behavior. Macromolecules 44:4496–4502

    Article  CAS  Google Scholar 

  57. Costa-Junior ES, Barbosa-Stancioli EF, Mansur AAP, Vasconcelos WL, Mansur HS (2009) Preparation and characterization of chitosan/poly(vinyl alcohol) chemically crosslinked blends for biomedical applications. Carbohydr Polym 76:472–481

    Article  CAS  Google Scholar 

  58. Domjan A, Fodor CS, Kovacs Sz, Marek T, Ivan B, Suvegh K (2012) Anomalous swelling behavior of poly(N-vinylimidazole)-l-poly(tetrahydrofuran) amphiphilic conetwork in water studied by solid-state NMR and positron annihilation lifetime spectroscopy. Macromolecules 45:7557–7565

    Article  CAS  Google Scholar 

  59. Fodor Cs, Ivan B (2011) Poly(N-vinylimidazole)-l-poly(tetrahydrofuran) amphiphilic conetworks and gels. II. Unexpected dependence of the reactivity of PTHF macromonomer cross-linker on molecular weight in copolymerization with N-vinylimidazole. J Polym Sci Part A Polym Chem 49:4729–4734

    Article  CAS  Google Scholar 

  60. Hayashi T, Knabe H, Okada M, Suzuki M, Ikeda Y, Onuki Y, Kaneko T, Sonobe T (2005) Formulation study and drug release mechanism of a new theophylline sustained-release preparation. Int J Pharm 304:91–101

    Article  CAS  Google Scholar 

  61. Kali G, Georgiou TK, Ivan B, Patrickios CS (2009) Anionic amphiphilic end-linked conetworks by the combination of quasiliving carbocationic and group transfer polymerizations. J Polym Sci Part A Polym Chem 47:4289–4301

    Article  CAS  Google Scholar 

  62. Kali G, Sz Vavra, Laszlo K, Ivan B (2013) Thermally responsive amphiphilic conetworks and gels based on poly(N-isopropylacrylamide) and polyisobutylene. Macromolecules 46:5337–5344

    Article  CAS  Google Scholar 

  63. Shin HS, Kim SY, Lee YM (1997) Indomethacin release behaviors from pH and thermoresponsive poly(vinyl alcohol) and poly(acrylic acid) IPN hydrogels for site-specific drug delivery. J Appl Polym Sci 65:685–693

    Article  CAS  Google Scholar 

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Acknowledgments

We thank the Faculty of Pharmacy B.Z. University, for providing laboratory facilities and Director, Centralized Resource Laboratory, Department of Physics, University of Peshawar, is acknowledged for providing us the facility of XRD.

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  1. Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Samiullah Khan & Nazar Mohammad Ranjha

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  1. Samiullah Khan
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Correspondence to Samiullah Khan.

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Khan, S., Ranjha, N.M. Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels. Polym. Bull. 71, 2133–2158 (2014). https://doi.org/10.1007/s00289-014-1178-2

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