PROCESS AND PARAMETERS AFFECTING DRUG RELEASE PERFORMANCE OF PREPARED CROSS-LINKED ALGINATE HYDROGEL BEADS FOR EZETIMIBE
Objective: The objective of this study was to formulate an oral sustained release delivery system of ezetimibe mucoadhesive beads by ionic gelation technique based on sodium alginate used as a hydrophilic carrier in combination with carbopol 934P which acts as a rate modifier.
Methods: Microbeads of ezetimibe were prepared using an easy method of ionotropic gelation by little modification while in addition of drug. The prepared beads were characterised for mean particle size, entrapment efficiency, swelling capacity, and in vitro release. They were also subjected to various studies such as Fourier Transform Infrared Spectrophotometer (FTIR) Spectroscopy for drug polymer reaction, Scanning Electron Microscopy for surface morphology, and Differential Scanning Calorimetric Analysis to determine the physical state of the drug in the beads.
Results: The microspheres of ezetimibe were formulated successfully. The addition of drug concentration gives higher drug loading and higher conc. of Alcl+3 yields small diameter beads and lower drug entrapment. Analysis of the release profiles showed that the data corresponds to zero order release and the diffusion-controlled mechanism as suggested by Higuchi concept.
Conclusion: It can be concluded that beads produced by the sequential method had higher drug entrapment. Beads produced by simultaneous yields larger beads in diameter. The concept was cleared that drug release was dependent upon the quantity of polymer and increase in conc. of. aluminium chloride retarded the drug release in the sequential method. Prepared beads enhance the dissolution of ezetimibe and the oral bioavailability and also reduce the fluctuations in the oral bioavailability.
2. Mangond BS, Sreedhar V, Baraskar W, Kulkarni RV. Development and evaluation of gellan gum based hydrogel microbeads for controlled release of ketoprofen. Indian J Novel Drug Delivery 2009;1:32-5.
3. Rajinikanth PS, Sankar C, Mishra B. Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: development and evaluation. Drug Delivery 2003;10:21-8.
4. McDowell RH. Properties of Alginates. 5th Edition. Kelco International, London; 1986.
5. Bruneton J. Algae polysaccharides. In: Pharmacognosy, phyto chemistry medicinal plants. 2nd ed. New York: Lavosier Publishing, Inc; 1999. p. 47â€“52.
6. Dhanaraju MD, Sundar VD, Nandha Kumar S, Bhaskar K. Development and evaluation of sustained delivery of diclofenac sodium from hydrophilic polymeric beads. J Young Pharm 2009;1:301.
7. Kikuchi A, Kawabuchi M, Sungihara M, Okano TS. Pulsed dextran releases from calcium alginate. J Controlled Release 1997;47:21-9.
8. Iannuccelli V. Bead coating process via an excess of a cross-linking agent. Drug Dev Ind Pharm 1995;21:307-22.
9. Tomida H. Imipramine releases from Ca-alginate gel beads. Chem Pharma Bull 1993;41:1475â€“7.
10. Gray CJ, Dowsett J. Retention of insulin in alginate gel beads. Biotechnol Bioeng 1988;31:607â€“12.
11. Sarmento B, Martins S, Ribeiro A, Veiga F, Neufeld R, Ferreira D. Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers. Int J Pept Res Ther 2006;12:131-8.
12. Bajpai SK, Sharma S. Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions. React Funct Polym 2004;59:129-40.
13. Kroll E, Winnik FM, Ziolo RF. In situ preparation of nanocrystalline Î³-Fe2O3 in iron (II) crosslinked alginate gels. Chem Mater 1996;8:1594â€“6.
14. Senuma Y, Lowe C, Zweifel Y, Hilborn JG, Marison I. Alginate hydrogel microspheres prepared by spinning disk automation. Biotechnol Bioeng 2000;67:616â€“22.
15. Kim CK, Lee EJ. The controlled release of blue dextran from alginate beads. Int J Pharm 1992;79:11-9.
16. Yotsuyanagi T, Ohkubo T, Ohhashi T, Ikeda K. Calcium-Induced gelation of alginic acid and pH-sensitive reswelling of dried gels. Chem Pharm Bull 1987;35:1555-63.
17. Tang YD, Venkatraman SS, Boey YC, Wang LW. Sustained release of hydrophobic and hydrophilic drugs from a floating dosage form. Int J Pharm 2007;336:159â€“65.
18. El-Kamel AH, Al-Gohary OMN, Hosny EA. Alginate-diltiazem hydrochloride beads: optimisation of formulation factors, in vitro and in vivo bioavailability. J Microencapsulation 2003;20:211â€“25.
19. Puttipipatkhachorn S. Xanthan-alginate composite gel beads molecular interactions and in vitro characterization. Int J Pharm 2007;331:61â€“71.
20. Pongjanyakul T, Priprem A. Molecular interactions in alginate beads reinforced with sodium starch glycolate or magnesium silicate, and their physical characteristics. Int J Pharm 2005;293:51â€“62.
21. Gal A, Nussinovitch A. Hydrocolloid carriers with filler inclusion for diltiazem hydrochloride release. J Pharm Sci 2007;96:168â€“78.
22. Smrdel P, Bogataj M, Planinsek O, Mrhar A. Shape optimization and characterization of polysaccharide beads prepared by ionotropic gelation. J Microencapsul 2008;25:90â€“105.
23. Ferreira Almeida P. Cross-linked alginate-gelatin beads: a new matrix for controlled release of pindolol. J Controlled Release 2004;97:431â€“9.
24. Lobenberg R, Amidon G. L, Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm 2000;50:3â€“12.
25. Park BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm 2013;85:799â€“813.
26. Portincasa P, Mendez-Sanchez N, Wang H, Uribe, Wang DQ. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastro Enterol 2008;134:2101â€“10.
27. Garg R, Gupta GD. Progress in controlled gastro retentive delivery systems. Trop J Pharm Res 2008;7:1055-66.
28. Sung-Joo Hwang, Gye Ju Rhee, Ki Myung lee, Kyoug-Hee Oh, Chong-Kook Kim. Release characteristics of Ibuprofen from excipients-loaded alginate gel beads. Int J Pharm 2005;116:125-8.
29. Nimmi I, Chowdhury JA, Dulal MM, Reza MS. Effects of electrolytes on diclofenac sodium from agarose beads. Dhaka Univ J Pharm Sci 2005;4:117-20.
30. Pornsak Sriamornsak, Kanokporn Burapapadh, Satit Puttipipatkhachorn, Jurairat Nunthanid. Effect of acidic medium on selling and release behaviours of chitosan reinforced calcium pectinate gel beads. Sci-Tech J 2008;2:37-44.
31. Forizs E, Patrut A, Cozar IB, David L. Synthesis, structure elucidation of palladium complexes with theophylline. Acad Romana Roum Chim 2010;55:697-704.
32. Patel R, Bhimani D, Patel J, Patel D. Solid-state characterization and dissolution properties of ezetimibe-cyclo dextrin inclusion complexes. J Inclusion Phenom Macrocyclic Chem 2008;60:241â€“51.
33. Sancheti PP, Karekar P, VM Vyas VM, Shah M, Pore YV. Preparation and physicochemical characterization of surfactant based solid dispersions of ezetimibe. Pharmazie 2009;64:227â€“31.
34. Ostberg T, Vesterhus L, Graffner C. Calcium alginate matrices for oral multiple unit administration: II. Effect of process and formulation factors on matrix properties. Int J Pharm 1993;97:183â€“93.
35. Smrdel P, Bogataj M, Podlogar F, Planinsek O, Zajc N, Mazaj M, et al. Characterization of calcium alginate beads containing structurally similar drugs. Drug Dev Ind Pharm 2006;32:623â€“33.
36. Nunthanid J, Sriamornsak P. Calcium alginate gel beads for controlled release drug delivery: II. Effect of formulation and processing variables on drug release. J Microencapsul 1999;16:303â€“13.
37. Aslani P, Kennedy RA. Studies on diffusion in alginate gels. I. Effect of cross-linking with calcium or zinc ions on the diffusion of acetaminophen. J Controlled Release 1996;42:75â€“82.
38. Sriamornsak P. Investigation of pectin as a carrier for oral delivery of proteins using calcium pectinate gel beads. Int J Pharm 1998;169:213â€“20.
39. Larson I, Dass CR, Choong PF, Dunstan DE. A chitosan dipotassium orthophosphate hydrogel for the delivery of doxorubicin in the treatment of osteosarcoma. Biomaterials 2009;2:213-20.
40. Nayak AK, Hasnain MS, Beg S, Alam M. Mucoadhesive beads of gliclazide: Design, development and evaluation. Sci Asia 2010;36:319-25.
41. Nutan MTH, Soliman MS, Taha EI, Khan MA. Optimisation and characterization of controlled release multi-particulate beads coated with starch acetate. Int J Pharm 2005;294:89â€“101.
42. Takka, Gombotz WR, Wee SF. Protein releases from alginate matrices. Adv Drug Delivery Rev 1998;31:267-85.
43. 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.
44. Takka S, Ocak O, Acarturk OHF. Formulation and investigation of nicardipine HCl-alginate gel beads with factorial design-based studies. Eur J Pharm Sci 1998;6:241â€“6.
45. Ostberg T. Thesis, University of Oslo, Oslo, Norway; 1994.
46. Gaserod O. Thesis, Norwegian University of Science and Technology, Trondheim, Norway; 1998.
47. Sakhare SS, Yadav AV, Jadhav PD. Design, development and characterization of mucoadhesive gastro spheres of carvedilol. Int J Appl Pharm 2016;8:37-42.