In vitro and Mechanism Study of Poly(ethylene-co-vinyl acetate)-Based Implant for Sustained Release of Vitamin B12

Chi Zhang; Allan J. Easteal; Neil R. Edmonds; Genhai Liang; Majid Razzak; Wayne Leech

Macromolecular Research, Vol.18, No.7, 653-659, July, 2010

DOI10.1007/s13233-010-0711-x Export Citation

In vitro and Mechanism Study of Poly(ethylene-co-vinyl acetate)-Based Implant for Sustained Release of Vitamin B12

Chi Zhang^†, Allan J. Easteal, Neil R. Edmonds, Genhai Liang, Majid Razzak¹, and Wayne Leech¹

Chemistry Department, University of Auckland, Auckland, New Zealand
¹Bomac Laboratories Ltd, Auckland, New Zealand

E-mail:

A polymer-vitamin B12 implant system has been developed to overcome the disadvantages of traditional vitamin B12 administration to sheep. The ethylene/vinyl acetate (EVAc) copolymer was pre-blended with crystalline vitamin B12. The blends were then extruded at 100 ℃ at a constant pressure and rate using a piston extruder to form a polymer-vitamin B12 composite cord. The final implant was a cylinder 2 mm in diameter and 4 mm in length. Determination of the rate of vitamin B12 release from the implant into a pH7.4 phosphate buffer at 37 ℃ showed that the release rate was strongly dependent on the feed concentration, size and shape of vitamin B12 crystals. The well-known Korsmeyer-Peppas exponential equation was applied to and the release mechanism was found to be a typical anomalous transport mechanism with a strong diffusion-controlled feature between pure diffusion-controlled and Case-II transport mechanisms because the n values obtained were between 0.45 and 0.51 for most polymer-vitamin B12 cylindrical implant systems.

Keywords:cobalt deficiency;vitamin B12;implant;in vitro release;mechanism;ethylene/vinyl acetate (EVAc) copolymer

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[1] Alexandrova R, Tudose R, Arnaudova E, Costisor O, Patron L, Exp. Pathol. Parasitol., 7, 3 (2004)

[2] McLaren DG, Hashmi SZ, Tucker IG, Abdul-Razzak MH, Xiahong ML, GB99-17757 2340395, 19990729 (2000).

[3] Oh R, David LB, Am. Family Physician, 67, 979 (2003)

[4] Baik HW, Russell RM, Annu. Rev. Nutrition, 19, 357 (1999)

[5] Judson GJ, Babidge PJ, Aust. Veterinary J., 80, 777 (2002)

[6] Grace ND, Knowles SO, Sinclair GR, Lee J, New Zealand Veterinary J., 51, 89 (2003)

[7] Grace ND, West DM, Sargison ND, New Zealand Veterinary J., 46, 194 (1998)

[8] Folkers K, Abstracts Communs. 1st Intern. Congr. Biochem., 86 (1949)

[9] Rickes EL, Wood TR, Vitamin B12. 2563794 (1951).

[10] Williams RR, Waterman RE, J. Biol. Chem., 68, 499 (1926)

[11] Tsai CW, Morris MD, Anal. Chim. Acta, 76, 193 (1975)

[12] Wang X, Wei L, Kotra LP, Bioorg. Med. Chem., 15, 1780 (2007)

[13] Lee DSC, Griffiths BW, Clin. Biochem., 18, 261 (1985)

[14] Goldstein S, Duca A, Thermochim. Acta, 59, 211 (1982)

[15] Giurginca M, Popa L, Zaharescu T, Polym. Degrad. Stabil., 82, 463 (2003)

[16] Dupont Elvax resins Product Data Sheet. http:// www2. dupont. com/ Elvax/ en_ US/ assets/ downloads.

[17] Sinha VR, Bansal K, Kaushik R, Kumria R, Trehan A, Int. J. Pharm., 278, 1 (2004)

[18] Bogoeva-Gaceva G, Avella M, Malinconico M, Buzarovska A, Grozdanov A, Gentile G, Errico ME, Polym. Compos., 28, 98 (2007)

[19] Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA, J. Pham. Sci., 72, 1189 (1983)

[20] Papadopoulou V, Kosmidis K, Vlachou M, Macheras P, Int. J. Pharm., 309, 44 (2006)

[21] Siepmann J, Peppas NA, Adv. Drug Deliver. Rev., 48, 139 (2001)

[22] van Dijkhuizen-Radersma R, Peters FLAMA, Stienstra NA, Grijpma DW, Feijen J, de Groot K, Bezemer JM, Biomaterials, 12, 1527 (2002)

[23] Kosmidis K, Argyrakis P, Macheras P, J. Chem. Phys., 119(12), 6373 (2003)