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An Epichlorohydrin-Crosslinked Semi-Interpenetrating GG-PEO Network as a Xerogel Matrix for Sustained Release of Sulpiride

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Abstract

The current study involved the development of a novel sustained release crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as crosslinker. A Box–Behnken design was employed for the statistical optimization of the matrix system to ascertain the ideal combination of native polymeric and crosslinking agents. Characterization studies were performed by employing standard polymer characterization techniques such as Fourier transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy. Formulated matrix tablets displayed zero-order release kinetics, extending over 24 h. The mechanism of drug release was primarily by swelling and surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non-crosslinked polymer blends; results from the study conducted showed that the physiochemical properties of the PEO and GG were sufficiently modified to allow for sustained release of sulpiride with a 100% drug release at 24 h in a controlled manner as compared to non-crosslinked formulations which displayed further release beyond the test period. Crosslinked formulations displayed water uptake between 450 and 500% indicating a controlled rate of swelling and erosion allowing for sustained release. Surface morphology of the crosslinked system depicted a porous structure formed by interpenetrating networks of polymers, allowing for a greater degree of controlled penetration into the system affording it the ability to sustain drug release. Therefore, conclusively, based on the study performed, crosslinked PEO-GG allows for the sustained release of sulpiride from a hydrophilic semi-IPN xerogel matrix system.

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References

  1. Dürig T, Fassihi R. Guar-based monolithic matrix systems: effect of ionizable and non-ionizable substances and excipients on gel dynamics and release kinetics. J Control Release. 2002;80:45–56.

    Article  PubMed  Google Scholar 

  2. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73:121–36.

    Article  PubMed  CAS  Google Scholar 

  3. Tanaka N, Imai K, Okimoto K, Ueda S, Tokunaga Y, Ibuki R, et al. Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II): In vivo evaluation. J Control Release. 2006;112:51–6.

    Article  PubMed  CAS  Google Scholar 

  4. Shanmugam S, Manavalan R, Venkappayya D, Sundaramoorthy K, Mounnissamy VM, Hemalatha S, et al. Natural polymers and their applications. Nat Prod Rad. 2005;4:478–81.

    Google Scholar 

  5. Kulkarni VS, Butte KD, Rathod SS. Natural Polymers - A Comprehensive Review. Int J Pharm Biomed Sci. 2012;3:1597–613.

    Google Scholar 

  6. Krishnaraj K, Chanrasekar MJN, Nanjan MJ, Muralidharan S, Manikandan D. Development of Sustained release antipsychotic tablets using novel polysaccharide isolated from Delonix regia seeds and its pharmacokinetic studies. Int J Pharm. 2012;20:239–48.

    Google Scholar 

  7. Singh A, Sharma PK, Malviya R. Release Behaviour of Drugs from various Natural Gums and Polymers. Polym Med. 2011;41:73–80.

    CAS  Google Scholar 

  8. Cappello B, DeRosa G, Giannini L. Cyclodextrin containing polyethylene oxide tablets for the delivery of poorly soluble drugs: Potential as buccal delivery system. Int J Pharm. 2006;319:63–70.

    Article  PubMed  CAS  Google Scholar 

  9. National Toxicology Program. Report on Carcinogens. 12th Edition, Department of Health and Human Services. 2011; 12:180.

  10. Chiba R, Soukura M, Tatsuta S. Liquid Chromatography solid phase extraction and determination of Sulpiride in human serum by high performance liquid chromatography using electro generated chemiluminescence detection. Anal Lett. 2011;44:1559–69.

    Article  CAS  Google Scholar 

  11. Barnes TRE, Davison S, Ferrier IN, et al. Consensus statement on high dose Anti-psychotic medication. Royal College of Psychiatrics. 2006;1-51.

  12. Watanabe K, Sawano T, Terada K, Endo T, Sakata M, Sato J. Studies on Intestinal Absorption of Sulpiride (1): Carrier-Mediated Uptake of Sulpiride in the Human Intestinal Cell Line Caco-2. Biol Pharm Bull. 2002;25:885–90.

    Article  PubMed  CAS  Google Scholar 

  13. Sigma Aldrich, MDS (±) Sulpiride, Germany.

  14. Covielloa T, Alhaiquea F, Parisia C, Matricardia P, Bocchinfusob G, Grassi M. A new polysaccharidic gel matrix for drug delivery: preparation and mechanical properties. J Control Release. 2005;102:643–56.

    Article  Google Scholar 

  15. Choonara YE, Pillay V, Carmichael T, Danckwerts MP. An in vitro study of the design and development of a novel doughnut-shaped Minitab let for intraocular implantation. Int J Pharm. 2006;310:15–24.

    Article  PubMed  CAS  Google Scholar 

  16. Kreye F, Hamm G, Karrout Y, Legouffe R, Bonnel D, Siepmann F, et al. MALDI-TOF MS imaging of controlled release implants. J Control Release. 2012;161:98–108.

    Article  PubMed  CAS  Google Scholar 

  17. Scaccia S. Water determination in composite PEO-based polymer electrolytes by volumetric Karl Fischer titration method. Talanta. 2005;67:678–81.

    Article  PubMed  CAS  Google Scholar 

  18. Shah RB, Tawakkul MA, Khan MA. Comparative Evaluation of Flow for Pharmaceutical Powders and Granules. AAPS PharmSciTech. 2008;9:250–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Özeroglu C, Birdal A. Swelling properties of acrylamide-N, N′-methylene bis (acrylamide) hydrogels synthesized by using meso-2, 3-dimercaptosuccinic acid-cerium (IV) redox couple. Express Polym Lett. 2009;3:168–76.

    Article  Google Scholar 

  20. Reddy MM, Reddy JD, Moin A, Shivakumar HG. Formulation of Sustained –Release Matrix Tablets using Crosslinked Karaya Gum. Trop J Pharm Res. 2012;11:28–35.

    Article  CAS  Google Scholar 

  21. Murthy PSK, Mohan YM, Sreeramulu J, Raju KM. Semi IPNs of starch and poly (acrylamide-co-sodium methacrylate): Preparation, swelling and diffusion characteristics evaluation. J Reac Funct Polym. 2006;66:1482–93.

    Article  CAS  Google Scholar 

  22. Strübing S, Metz H, Mäder K. Characterization of poly (vinyl acetate) based floating matrix tablets. J Control Release. 2008;126:149–55.

    Article  PubMed  Google Scholar 

  23. Pillay V, Fassihi R. A novel approach for constant rate delivery of highly soluble bioactives from a simple monolithic system. J Control Release. 2000;67:67–78.

    Article  PubMed  CAS  Google Scholar 

  24. Ruvalcaba AM, Snchez-Diaz JC, Becerra F, Cruz-Barba LE, Gonzalez-Alvarez A. Swelling characterization and drug delivery kinetics of polyacrylamide-co-itaconic acid/chitosan hydrogels. Express Polym Lett. 2009;3:25–32.

    Article  Google Scholar 

  25. Khalid MN, Agnely F, Yagoubi N, Grossiord JL, Couarraze G. Water state characterization, swelling behaviour, thermal and mechanical properties of chitosan based networks. Eur J Pharm Sci. 2002;15:425–32.

    Article  PubMed  CAS  Google Scholar 

  26. Aulton ME. The Design and Manufacture of Medicines. Third Edition. Philadelphia. Elsevier. 2007;109–110.

  27. Ferrero C, Massuelle D, Deolker E. Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ether. II Evaluation of a possible swelling-controlled drug release mechanism using dimensionless analysis. J Control Release. 2010;141:223–33.

    Article  PubMed  CAS  Google Scholar 

  28. Ahuja G, Pathak K. Porous carriers for controlled/modulated drug delivery. Ind J Pharm Sci. 2009;71:599–607.

    Article  CAS  Google Scholar 

  29. Sriamornsak P, Thirawong N, Weerapol Y, Nunthanid J. Swelling and Erosion of pectin Matrix tablets and their impact on drug release behaviour. Eur J Pharm Biopharm. 2007;7:211–9.

    Article  Google Scholar 

  30. Kulkarni RV, Baraskar VV, Setty CM, Sa B. Interpenetrating Polymer Network Matrices of Sodium Alginate and Carrageenan for Controlled drug delivery application. J Fibres Polym. 2011;12:352–8.

    Article  CAS  Google Scholar 

  31. Kulkarni RV, Mangond BS, Mutalik S, Sa B. Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem–resin complex for controlled release application. Carb Polym. 2011;83:1001–7.

    Article  CAS  Google Scholar 

  32. Rokhade AP, Agnihotri SA, Patil SA, Malikarjuna NN, Kulkarni PV, Aminabhavi TM. Semi- Interpenetrating polymer network microspheres of gelatin and sodium Carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carb Polym. 2006;65:243–52.

    Article  CAS  Google Scholar 

  33. Szakonyi G, Zelkó R. The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form. Int J Pharm Invest. 2012;2:18–25.

    Article  CAS  Google Scholar 

  34. Ibrahim S, Johan MR. Thermolysis and Conductivity Studies of Poly (Ethylene Oxide) (PEO) Based Polymer Electrolytes Doped with Carbon Nanotube. Int J Electrochem Sci. 2012;7:2596–615.

    CAS  Google Scholar 

  35. Izumi Y, Saito S, Soma K. Differential Scanning Calorimetry and Structural studies of the sol-gel transition of gellan gum in water. Progress Colloid Polym Sci. 1999;114:48–55.

    Article  CAS  Google Scholar 

  36. Zo-li JTU. Morphology, Crystallization and Melting Behavior of Propylene-Ethylene Statistical Copolymers. Doctor of Philosophy. Virginia: Polytechnic Institute and State University. 2005;3–29.

  37. UserCom, 1/2000, Information for users of METTLER TORLEDO thermal analysis systems, Mettler Toledo. 2000;1–25.

  38. Reis MD, Pruitt L. Effects of cross-linking on the microstructure and mechanical properties of ultra- high molecular weight. Clin Orthopedic Res. 2005;440:149–56.

    Article  Google Scholar 

  39. Coates J. Interpretation of Infrared Spectra, A Practical Approach. In. Encyclopedia of Analytical Chemistry. R.A. Meyers (Ed.) 2000; pp. 10815–10837.

  40. Adel AM, Abou-Youssef H, El Gendy AA, Nada AM. Carboxymethylated Cellulose Hydrogel Sorption, Behaviour, and Characterization. Nature Sci. 2010;8:244–56.

    Google Scholar 

  41. Gulrez SKH, Al-Assaf S, Phillips GO. Hydrogels: Methods of Preparation, characterization and Applications. In. Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications. A. Carpi (Ed.) 2011; pp. 307–568.

  42. Toti US, Aminabhavi TM. Modified guar gum matrix tablet for controlled release of diltiazem hydrochloride. J Control Release. 2004;95:567–77.

    Article  PubMed  CAS  Google Scholar 

  43. Maderuelo C, Zarzuelo A, Lanao JM. Critical factors in the release of drugs from sustained release hydrophilic matrices. J Control Release. 2011;154:2–19.

    Article  PubMed  CAS  Google Scholar 

  44. Siepmann J, Lecomte F, Bodmeie R. Diffusion- controlled drug delivery systems: calculation of the required composition to achieve desired release profiles. J Control Release. 1999;60:379–89.

    Article  PubMed  CAS  Google Scholar 

  45. Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). J Adv Drug Del Rev. 2012;64:163–74.

    Article  Google Scholar 

  46. Shoaib MH, Tazeen J, Merchant HA, Yousuf RI. Evaluation Of Drug Release Kinetics From Ibuprofen Matrix Tablets Using HPMC. Pak J Pharm Sci. 2006;19:119–24.

    PubMed  CAS  Google Scholar 

  47. Reddy KR, Mutalik S, Reddy S. Once-Daily Sustained-Release Matrix Tablets of Nicorandil: Formulation and In Vitro Evaluation. AAPS PharmSciTech. 2003;4:1–9.

    Article  Google Scholar 

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Acknowledgements

This study was funded by the National Research Foundation (NRF) of South Africa.

Conflict on Interest

The Authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa

    Famida G. Hoosain, Yahya E. Choonara, Pradeep Kumar, Lomas K. Tomar, Charu Tyagi, Lisa C. du Toit & Viness Pillay

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  1. Famida G. Hoosain
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  2. Yahya E. Choonara
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  3. Pradeep Kumar
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  4. Lomas K. Tomar
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  6. Lisa C. du Toit
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  7. Viness Pillay
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Correspondence to Viness Pillay.

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Hoosain, F.G., Choonara, Y.E., Kumar, P. et al. An Epichlorohydrin-Crosslinked Semi-Interpenetrating GG-PEO Network as a Xerogel Matrix for Sustained Release of Sulpiride. AAPS PharmSciTech 15, 1292–1306 (2014). https://doi.org/10.1208/s12249-014-0153-4

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  • DOI: https://doi.org/10.1208/s12249-014-0153-4

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