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Enteric-coated Ca-alginate hydrogel beads: a promising tool for colon targeted drug delivery system

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Abstract

Enteric coating of hydrogel beads is an effective approach to resolve the drug entrapment problem reported in previous studies. In the present study, microencapsulation of drug in hydrogel beads with extrusion-dripping technique was used for the improvement of the drug entrapment efficiency. Calcium chloride dehydrate was used as a cross-linking agent and oil-in-oil solution of eudragit S-100 was used as coating material while diclofenac sodium was used as a model drug. Optical microscopy, scanning electron microscopy, weight, elemental, and size variation of prepared hydrogels beads were analyzed and found within the acceptable limits. The drug loading and release studies of the coated beads were evaluated. Retardation of the model drug in gastric and intestinal pH environment until 8 h was observed which made the prepared hydrogels more targeted and colon-specific. In acidic pH 1.2, negligible percentage release was observed, whereas at pH 7.4, 98% diclofenac sodium was estimated after 8 h. In vitro release, kinetic studies proved that concentration-dependent release behavior of diclofenac sodium followed Fick’s law of diffusion in coated form, while non-Fickian behavior was observed in uncoated beads. Prepared hydrogel beads may be used as a promising tool for sustained release of drug targeting colon.

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References

  1. Paharia A, Yadav AK, Rai G, Jain SK, Pancholi SS, Agrawal GP (2007) Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting. AAPS PharmSciTech 8(1):E87–E93

    Article  Google Scholar 

  2. Wang Q, Xie X, Zhang X, Zhang J, Wang A (2010) Preparation and swelling properties of pH-sensitive composite hydrogel beads based on chitosan-g-poly (acrylic acid)/vermiculite and sodium alginate for diclofenac controlled release. Int J Biol Macromol 46(3):356–362

    Article  CAS  Google Scholar 

  3. Chan E-S, Lee B-B, Ravindra P, Poncelet D (2009) Prediction models for shape and size of ca-alginate macrobeads produced through extrusion–dripping method. J Colloid Interface Sci 338(1):63–72

    Article  CAS  Google Scholar 

  4. Dai YN, Li P, Zhang JP, Wang AQ, Wei Q (2008) Swelling characteristics and drug delivery properties of nifedipine-loaded pH sensitive alginate–chitosan hydrogel beads. J Biomed Mater Res B Appl Biomater 86(2):493–500

    Article  Google Scholar 

  5. Arvapalli S, Nandini P, Sharma R, Sharma J (2019) Design, characterization and evaluation of hydrogel beads of dalfampridine using synthetic polymers

  6. Kusuma KNM, Swathi B, Ramkanth S, Kusuma S (2014) Formulation and evaluation of Losartan hydrogel beads. Int J Pharm Drug Anal 2:788–795

    Google Scholar 

  7. Rai G, Yadav AK, Jain NK, Agrawal GP (2016) Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon. Drug Deliv 23(1):328–337

    Article  CAS  Google Scholar 

  8. Agüero L, Zaldivar-Silva D, Peña L, Dias ML (2017) Alginate microparticles as oral colon drug delivery device: a review. Carbohyd Polym 168:32–43

    Article  Google Scholar 

  9. Pervez S, Nawaz MA, Aman A, Qayyum S, Nawaz F, Qader SAU (2018) Agarose hydrogel beads: an effective approach to improve the catalytic activity, stability and reusability of fungal amyloglucosidase of GH15 family. Catal Lett 148(9):2643–2653

    Article  CAS  Google Scholar 

  10. Gombotz WR, Wee SF (2012) Protein release from alginate matrices. Adv Drug Deliv Rev 64:194–205

    Article  Google Scholar 

  11. Nochos A, Douroumis D, Bouropoulos N (2008) In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohyd Polym 74(3):451–457

    Article  CAS  Google Scholar 

  12. Bajpai S, Sharma S (2004) Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions. React Funct Polym 59(2):129–140

    Article  CAS  Google Scholar 

  13. Buss A, Locs J Effects of calcium and alginate concentration on the calcium-deficient hydroxyapatite hydrogel bead formation. In: Key engineering materials, 2017. Trans Tech Publications, pp 187–191

  14. Giri TK, Dey B, Maity S (2018) Preparation and characterization of nanoemulsome entrapped in enteric coated hydrogel beads for the controlled delivery of capsaicin to the colon. Curr Drug Ther 13(1):98–105

    Article  CAS  Google Scholar 

  15. Obeidat WM, Price JC (2006) Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method. J Microencapsul 23(2):195–202

    Article  CAS  Google Scholar 

  16. Chawla A, Sharma P, Pawar P (2012) Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: formulation, optimization and in vitro evaluation/Alginatne mikrosfere naproksen natrija obložene Eudragitom S-100: Priprava, optimizacija i in vitro vrednovanje. Acta Pharmaceutica 62(4):529–545

    Article  CAS  Google Scholar 

  17. Deshmukh R, Harwansh RK, Paul SD, Shukla R (2020) Controlled release of sulfasalazine loaded amidated pectin microparticles through Eudragit S 100 coated capsule for management of inflammatory bowel disease. J Drug Deliv Sci Technol 55:101495

    Article  CAS  Google Scholar 

  18. Altman R, Bosch B, Brune K, Patrignani P, Young C (2015) Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs 75(8):859

    Article  CAS  Google Scholar 

  19. Lorenzo-Lamosa M, Remunan-Lopez C, Vila-Jato J, Alonso M (1998) Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release 52(1):109–118

    Article  CAS  Google Scholar 

  20. Park TG, Hoffman AS (1992) Preparation of large, uniform size temperature-sensitive hydrogel beads. J Polym Sci, Part A: Polym Chem 30(3):505–507

    Article  CAS  Google Scholar 

  21. Ahn J-S, Choi H-K, Chun M-K, Ryu J-M, Jung J-H, Kim Y-U, Cho C-S (2002) Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly (acrylic acid) in vitro. Biomaterials 23(6):1411–1416

    Article  CAS  Google Scholar 

  22. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15(1):25–35

    Article  CAS  Google Scholar 

  23. Murata Y, Miyamoto E, Kawashima S (1996) Additive effect of chondroitin sulfate and chitosan on drug release from calcium-induced alginate gel beads. J Controlled Release 38(2–3):101–108

    Article  CAS  Google Scholar 

  24. Merakchi A, Bettayeb S, Drouiche N, Adour L, Lounici H (2019) Cross-linking and modification of sodium alginate biopolymer for dye removal in aqueous solution. Polym Bull 76(7):3535–3554

    Article  CAS  Google Scholar 

  25. Lee BB, Ravindra P, Chan ES (2013) Size and shape of calcium alginate beads produced by extrusion dripping. Chem Eng Technol 36(10):1627–1642

    CAS  Google Scholar 

  26. Yoo MK, Choi HK, Kim TH, Choi YJ, Akaike T, Shirakawa M, Cho CS (2005) Drug release from xyloglucan beads coated with Eudragit for oral drug delivery. Arch Pharmacal Res 28(6):736

    Article  CAS  Google Scholar 

  27. Pasparakis G, Bouropoulos N (2006) Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate–chitosan beads. Int J Pharm 323(1):34–42

    Article  CAS  Google Scholar 

  28. Weng L, Tessier SN, Swei A, Stott SL, Toner M (2017) Controlled ice nucleation using freeze-dried Pseudomonas syringae encapsulated in alginate beads. Cryobiology 75:1–6

    Article  CAS  Google Scholar 

  29. Hua S, Ma H, Li X, Yang H, Wang A (2010) pH-sensitive sodium alginate/poly (vinyl alcohol) hydrogel beads prepared by combined Ca2+ crosslinking and freeze-thawing cycles for controlled release of diclofenac sodium. Int J Biol Macromol 46(5):517–523

    Article  CAS  Google Scholar 

  30. Thakral NK, Ray AR, Majumdar DK (2010) Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer. J Mater Sci Mater Med 21(9):2691–2699

    Article  CAS  Google Scholar 

  31. Palomo M, Ballesteros M, Frutos P (1999) Analysis of diclofenac sodium and derivatives. J Pharm Biomed Anal 21(1):83–94

    Article  CAS  Google Scholar 

  32. Chiew CSC, Yeoh HK, Pasbakhsh P, Poh PE, Tey BT, Chan ES (2016) Stability and reusability of alginate-based adsorbents for repetitive lead (II) removal. Polym Degrad Stab 123:146–154

    Article  CAS  Google Scholar 

  33. Shivakumar H, Desai B, Deshmukh G (2008) Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology. Indian J Pharm Sci 70(1):22

    Article  CAS  Google Scholar 

  34. Mehta R, Chawla A, Sharma P, Pawar P (2013) Formulation and in vitro evaluation of Eudragit S-100 coated naproxen matrix tablets for colon-targeted drug delivery system. J Adv Pharm Technol Res 4(1):31

    Article  CAS  Google Scholar 

  35. Elnashar MM, Yassin MA, Moneim A, El-Fetouh A, Abdel Bary EM (2010) Surprising performance of alginate beads for the release of low-molecular-weight drugs. J Appl Polym Sci 116(5):3021–3026

    CAS  Google Scholar 

  36. Dainty A, Goulding K, Robinson P, Simpkins I, Trevan M (1986) Stability of alginate-immobilized algal cells. Biotechnol Bioeng 28(2):210–216

    Article  CAS  Google Scholar 

  37. Rodrı́guez M, Vila-Jato JL, Torres D (1998) Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region. J Control Release 55(1):67–77

    Article  Google Scholar 

  38. Khan M, Sridhar B, Srinatha A (2010) Development and evaluation of pH-dependent micro beads for colon targeting. Indian J Pharm Sci 72(1):18

    Article  CAS  Google Scholar 

  39. Fernandez-Hervas M, Holgado M, Fini A, Fell J (1998) In vitro evaluation of alginate beads of a diclofenac salt. Int J Pharm 163(1):23–34

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, Bahauddin Zakariya University, Multan, Multan, Pakistan

    Sadia Rehman, Muhammad Hanif, Abdul Majed & Nabeela Ameer

  2. Department of Pharmacy, Railway Road Campus, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

    Sadia Rehman

  3. Department of Pharmacy, The University of Lahore, Gujrat Campus, GT Road, Gujrat, Pakistan

    Nazar Muhammad Ranjha

  4. Department of Mechanical Engineering, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan

    M. Rafi Raza

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  1. Sadia Rehman
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  2. Nazar Muhammad Ranjha
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  3. M. Rafi Raza
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  4. Muhammad Hanif
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  5. Abdul Majed
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  6. Nabeela Ameer
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Correspondence to Sadia Rehman or M. Rafi Raza.

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Rehman, S., Ranjha, N.M., Raza, M.R. et al. Enteric-coated Ca-alginate hydrogel beads: a promising tool for colon targeted drug delivery system. Polym. Bull. 78, 5103–5117 (2021). https://doi.org/10.1007/s00289-020-03359-1

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  • DOI: https://doi.org/10.1007/s00289-020-03359-1

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