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Formulation and Evaluation of Cyperus esculentus (Tiger Nut) Starch-Alginate Microbeads in the Oral Delivery of Ibuprofen

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Abstract

Purpose

Microencapsulation is a technique employed in the development of controlled drug delivery systems. It is beneficial in reducing dosing frequency, ensuring targeted drug delivery, and improving drug bioavailability. The objective of this study was to evaluate the effectiveness of Cyperus esculentus starch and its derivative in the development of microbeads for sustained delivery of ibuprofen.

Methods

Ibuprofen-loaded microbeads were prepared by ionotropic gelation using Cyperus esculentus starch and its derivative in combination with sodium alginate at concentrations of 1:1, 1:2, and 2:1 and calcium chloride solution as cross-linker. Morphology of the microbeads by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), and differential scanning calorimetry (DSC) were investigated. Entrapment efficiency, swelling capacity, mucoadhesion, and in vitro drug release were also evaluated.

Results

SEM showed that the microbeads were spherical to irregular in shape, FT-IR returned prominent peaks specific for ibuprofen and absence of new peaks, DSC revealed evidence of entrapment of ibuprofen in the microbeads, and entrapment efficiency ranged between 46.05 and 89.86%. Microbeads prepared with native and cross-linked starches showed better mucoadhesion, and those prepared with cross-linked starch blend exhibited highest swelling capacity. In vitro release was pH dependent, and increasing the concentration of cross-linked starch in the blend caused greater retardation of drug release (45.19%) than the formulations containing native starch-alginate blend or sodium alginate alone.

Conclusion

The blend of cross-linked Cyperus esculentus starch and sodium alginate shows propensity to sustain ibuprofen release and could be exploited for targeted delivery especially to the lower GIT.

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References

  1. Kumar VV, Sivakumar T, Tamizh TM. (2011). Colon targeting drug delivery system: a review on recent approaches. Int J Pharm Bio Sci. 2011;2(1):11–9.

    CAS  Google Scholar 

  2. Berkland C, Kipper MJ, Narasimhan B, Kim KK, Pack DW. Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres. J Ctrl Rel. 2004;8:129–41.

    Google Scholar 

  3. Patil P, Chavanke D, Wagh M. A review on ionotropic gelation method: novel approach for controlled gastroretentive gelispheres. Int J Pharm Pharm Sci. 2012;4:27–32.

    CAS  Google Scholar 

  4. Belyaeva E, Valle DD, Neufeld RJ, Ponceleta D. New approach to the formulation of hydrogel beads by emulsification/thermal gelation using a static mixer. Chem Eng Sci. 2004;59(2):2913–20.

    Article  CAS  Google Scholar 

  5. Aswathy KS, Abraham AM, Jomy L, Mehaladevi R, John RK. Formulation and evaluation of Etodolac alginate beads prepared by ionotropic gelation for sustained release. J Sci Innov Res. 2014;3:527–53.

    Article  Google Scholar 

  6. Fontes GC, Calado VMA, Rossi AM, Miguez da Rocha-Leão HM. Characterization of antibiotic-loaded alginate-OSA starch microbeads produced by ionotropic pregelation. Biomed Res Int. 2013:1–12.

  7. Hari BNV, Praneeth T, Prathyusha T, Mounika K, Devi DR. Development of starch-gelatin complex microspheres as sustained release delivery system. J Adv Pharm Tech Res. 2012;3:182–7.

    Article  CAS  Google Scholar 

  8. Okunlola A, Adewusi SA. Development of theophylline microbeads using pregelatinized breadfruit starch (Artocarpus altilis) as a novel co-polymer for controlled release. Adv Pharm Bull. 2019;9:93–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Blemur L, Canh T, Marococci L, Pietrangeli P, Mateescu MA. Carboxymethyl starch/alginate microspheres containing diamine oxidase for intestinal targeting. Biotechnol Appl Biochem. 2016;63:344–53.

    Article  CAS  PubMed  Google Scholar 

  10. Jha A, Bhattachraya A. Preparation and evaluation of sweet potato starch-blended sodium alginaye microbeads. Asian J Pharm. 2009;3:229–303.

    Article  Google Scholar 

  11. Biswas N, Sahoo RK. Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of metoprolol tartrate. Int J Biol Macromol. 2016;83:61–70.

    Article  CAS  PubMed  Google Scholar 

  12. Kim YJ, Kim J, Park GH, Yang YL, Yoon Y, Kim S, et al. Multifunctional drug delivery system using starch-alginate beads for controlled release. Biol Pharm Bull. 2005;28:394–7.

    Article  CAS  PubMed  Google Scholar 

  13. Leo E, Forni F, Bernabe MT. Surface drug removal from ibuprofen-loaded PLA microspheres. Int J Pharm. 2000;196:1–9.

    Article  CAS  PubMed  Google Scholar 

  14. Malakar J, Nayak AK, Das A. Modified starch (cationized)-alginate beads containing aceclofenac: formulation optimization, using central composite design. Starch-Starke. 2013;65:603–12.

    Article  CAS  Google Scholar 

  15. Rapee KR, Wirinta K, Pongjanyakul TT. Modification of alginate beads using gelatinized and ungelatinized arrowroot (Tacca leontopetaloides) starch for drug delivery. Int J Biol Macromol. 2018;118:683–92.

    Article  CAS  Google Scholar 

  16. Fontes GC, Finotelli PV, Rossi AM, Rocha-Leão MHM. Optimization of penicillin G microencapsulation with OSA starch by factorial design. Chem Eng Trans. 2012;27:85–90.

    Google Scholar 

  17. Martins M, Barros AA, Quraishi S, Gurikov P, Raman SP, Smirnova I, et al. Preparation of macroporous alginate-based aerogels for biomedical applications. J Supercrit Fluids. 2015;106:152–7.

    Article  CAS  Google Scholar 

  18. Feng J, Dou J, Wu Z, Yin D, Wu W. Controlled release of biological control agents for preventing aflatoxin contamination from starch-alginate beads. Molecules. 2019;24:1858.

    Article  CAS  PubMed Central  Google Scholar 

  19. Onyido I, Sha’Ato R, Nnamonu LA. Environmentally friendly formulations of Trifluralin based on alginate modified starch. J Environ Prot. 2012;3:1085–93.

    Article  CAS  Google Scholar 

  20. Singh B, Sharma DK, Gupta A. The controlled and sustained release of a fungicide from starch and alginate beads. J Environ Sci Health. 2009;44:113–22.

    Article  CAS  Google Scholar 

  21. Hoover R. Composition, molecular structure, and physicochemical properties of tuber and root starches: a review. Carbohydr Polym. 2001;45:253–67.

    Article  CAS  Google Scholar 

  22. Morthy SN. Starch and starch derivatives in food. Trends Carbohyd Chem. 1996;425:133–9.

    Google Scholar 

  23. Abano EE, Amoah KK. Effect of moisture content on the physical properties of tigernut (Cyperus esculentus). Asian J Agric Res. 2001;5:56–66.

    Google Scholar 

  24. Rubert J, Sebastià N, Soriano JM, Soler C, Mañes J. One-year monitoring of aflatoxins and ochratoxin a in tiger-nuts and their beverages. Food Chem. 2011;127:822–6.

    Article  CAS  PubMed  Google Scholar 

  25. Azubuike CP, Fabiyi RO, Oseni BA, Igwilo CI. Evaluation of disintegrant potential of carboxymethyl starch derived from Cyperus esculentus (Cyperaceae) tubers. Trop J Nat Prdt Res. 2019;3:246–51.

    CAS  Google Scholar 

  26. Builders PF, Anwunobi PA, Mbah CC, Adikwu MA. New direct compression excipient from tigernut starch: physicochemical and functional properties. AAPS PharmSciTech. 2013;14:818–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Okorie O, Azaka JE, Ibeshi E. Evaluation of the suspending properties of cyperus esculentus (Tiger nut) starch in sulphadimidine suspension. Am J Biomed Sci Eng. 2016;1:1–7.

    Google Scholar 

  28. Onyinye DO, Azubuike CP, Aloko S, Ologunagba MO, Igwilo CI. Characterization and disintegrant potential of phosphorylated tiger nut (Cyperus esculentus) starch in immediate release ibuprofen tablet formulation. Dhaka Univ J Pharm Sci. 2019;18:21–9.

    Article  CAS  Google Scholar 

  29. Olayemi B, Isimi CY, Ekere K, Ajeh JI, Okoh JE, Emeje M. Green preparation of citric acid cross-linked starch for improvement of physico-chemical properties of Cyperus starch. In press; Turkish J Pharm. 2020. https://doi.org/10.4274/tjps.65624.

  30. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. N Engl J Med. 1999;340:1888–99.

    Article  CAS  PubMed  Google Scholar 

  31. Hemalatha CH, Vasavi G, Kumar A, Sriram N. Formulation and development of gliclazide microspheres for pharmaceutical evaluations. Int J Adv Pharm. 2014;4:83–92.

    Google Scholar 

  32. Sharma VK, Bhattacharya A. Release of metformin hydrochloride from Ispaghula-sodium alginate beads adhered on cock intestinal mucosa. Indian J Pharm Educ Res. 2008;42:363–70.

    Google Scholar 

  33. Siepmann J, Streubel A, Peppas NA. Understanding and predicting drug delivery from hydrophilic matrix tablets using the sequential layer model. Pharm Res. 2002;19:306–14.

    Article  CAS  PubMed  Google Scholar 

  34. Artifin DY, Lee LY, Wang CH. Mathematical modeling and simulation of drug release from microspheres: implication to drug delivery systems. Adv Drug Deliv Rev. 2006;58:1274–325.

    Article  CAS  Google Scholar 

  35. Al-Musa S, Fara DA, Badwan AA. Evaluation of parameters involved in preparation and release of drug loaded in crosslinked matrices of alginate. J Ctrl Rel. 1999;57:223–32.

    CAS  Google Scholar 

  36. Odeku OA, Okunlola A, Lamprecht A. Microbead design for sustained drug release using four natural gums. Int J Biol Macromol. 2013;58:113–20.

    Article  CAS  PubMed  Google Scholar 

  37. Akin-Ajani OD, Ajala TO, Ikehin M. Date mucilage as co-polymer in metformin-loaded microbeads for controlled release. J Excip Food Chem. 2019;10:3–12.

    Google Scholar 

  38. Martic M, Tatic I, Markovic S, Kujundzic N, Kostrun S. Synthesis, biological activity and molecular modelling studies of novel COX-1 inhibitors. Eur J Med Chem. 2004;39:141–51.

    Article  CAS  PubMed  Google Scholar 

  39. Mahaveer DK, Anandrao RK, Mahadevappa YK, Tejraj MA. In vitro release study of verapamil hydrochloride through sodium alginate interpenetrating monolithic membranes. Drug Dev Ind Pharm. 2001;27:1107–14.

    Article  Google Scholar 

  40. Pahwa R, Kumar V, Kohli K. Alginate beads prepared by ionotropic gelation technique: formulation design. Res J Chem Sci. 2015;5:45–7.

    Google Scholar 

  41. Singh PK, Shukla TS, Easwari TS, Kumar S, Chudhary R. Formulation development and evaluation of mucoadhesive oral dosage form containing clarithromycin using different mucoadhesive polymers. Int J Pharm Sci Health Care. 2012;2:159–71.

    Google Scholar 

  42. Shivhare UD, Marthar VB, Shrivastava CG, Ramteke VI. Preparation of microbeads by different techniques and study of their influence. J Adv Pharm Educ Res. 2013;3:279–89.

    Google Scholar 

  43. Al-Kassas RS, Al-Gohary OMN, Al-Faadhel MM. Controlling of systemic absorption of gliclazide through incorporation into alginate beads. Int J Pharm. 2007;341:230–7.

    Article  CAS  PubMed  Google Scholar 

  44. Deasy PB, Collins AEM, Maccarthy DJ, Russell RJ. Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. J Pharm Pharmacol. 1989;41:694–9.

    Article  CAS  PubMed  Google Scholar 

  45. Kowalski G, Kijowska K, Witczak K, Kuterasiński K, Łukasiewicz M. Synthesis and effect of structure on swelling properties of hydrogels based on high methylated pectin and acrylic polymers. Polymers. 2019;11:1–16.

    Article  CAS  Google Scholar 

  46. Alexander A, Ajazuddin S, Tripathi DK, Verma T, Maurya J, Patel S. Mechanism responsible for mucoadhesion of mucoadhesive drug delivery system: a review. Int J Appl Biol Pharm Technol. 2011;2:434–45.

    Google Scholar 

  47. Jelvehgari M, Vajihe M, Seyed HM. Preparation and evaluation of mucoadhesive beads/discs of alginate and algino-pectinate of piroxicam for colon-specific drug delivery via oral route. Jundishapur J Nat Pharm Prdt. 2014;9:1–10.

    Article  Google Scholar 

  48. Cui S, Yao B, Gao M, Sun X, Gou D, Hu J, et al. Effects of pectin structure and crosslinking method on the properties of cross-linked pectin nanofibers. Carbohydr Polym. 2017;157:766–74.

    Article  CAS  PubMed  Google Scholar 

  49. Khan AB, Mahamana R, Pal E. Review on mucoadhesive drug delivery system: novel approaches in modern era. RGUHS J Pharm Sci. 2014;4:128–41.

    Article  Google Scholar 

  50. Raida S. Controlling of systemic absorption of gliclazide through incorporation into alginate beads. J Microencapsul. 2007;341:230–7.

    Google Scholar 

  51. El Maghraby GM, El Zayat EM, Al Anazi FK. Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan. Drug Dev Ind Pharm. 2012;38:971–8.

    Article  PubMed  CAS  Google Scholar 

  52. Narra K, Dhanalekshmi U, Rangaraj G, Raja D, Kumar CS, Reddy PN, et al. Effect of formulation variables on rifampicin loaded alginate beads. Iranian J Pharm Res. 2012;11:715–21.

    CAS  Google Scholar 

  53. Shah VP, Tsong Y, Sathe P, Liu JP. In-vitro dissolution profile comparison-statistics and analysis of the similarity factor, f2. Pharm Res. 1998;5:889–96.

    Article  Google Scholar 

  54. Turner S, Federici C, Hite M, Fassihi R. Formulation development and human in-vitro/in-vivo correlation fora novel, monolithic controlled-release matrix system of high load and highly water-soluble drug niacin. Drug Dev Ind Pharm. 2004;30(8):797–807.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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Acknowledgments

The authors appreciate the staff of the Department of Pharmaceutical Technology and Raw Materials Development for the support received during the course of this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Raw Materials Development, National Institute for Pharmaceutical Research and Development (NIPRD), Idu Industrial Area, P.M.B. 21 Garki, Abuja, FCT, Nigeria

    Olubunmi J. Olayemi & Christianah Y. Isimi

  2. Department of Pharmaceutics and Industrial Pharmacy, Ahmadu Bello University, Zaria, Nigeria

    Yonni E. Apeji

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  1. Olubunmi J. Olayemi
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Correspondence to Olubunmi J. Olayemi.

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Olayemi, O.J., Apeji, Y.E. & Isimi, C.Y. Formulation and Evaluation of Cyperus esculentus (Tiger Nut) Starch-Alginate Microbeads in the Oral Delivery of Ibuprofen. J Pharm Innov 17, 366–375 (2022). https://doi.org/10.1007/s12247-020-09509-2

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