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Preparation and in Vitro Release of Melatonin-Loaded Multivalent Cationic Alginate Beads

Lee, Beom-Jin    (College of Pharmacy, Kangwon National University   ); Min, Geun-Hong    (College of Pharmacy, Kangwon National University   ); Kim, Tae-Wan    (College of Pharmacy, Kangwon National University  );
  • 초록

    The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$ . The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++} the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.


  • 주제어

    Melationin .   Multivalent cationic alginate beads .   SEM .   Release .   profiles .   Trapping efficiency.  

  • 참고문헌 (18)

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    7. The controlled release of prednisolone using alginate gel , Sugawara,S.;Imai,T.;Otagiri,M. , Pharm. Res. / v.11,pp.272-277,
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    9. Calcium alginate matrices for oral multiple unit administration: II. Effect of process and formulation factors on matrix properties , Ostberg,T.;Vesterhus,L.;Graffner,C. , Int. J. Pharm. / v.97,pp.183-193,
    10. Plasma melatonin (M) and Sulfatoxymelatonin (aMT6s) kinetics after transmucosal administration to humans. Melatonin and the pineal gland from basic science to clinical application , Benes,L.;Brun,J.;Claustrat,B.;Degrande,G.;Ducloux,N.;Geoffriau,M.;Horriere,F.;Karsenty,H.;Lagain,D. , Proceedings from the congress on pineal gland / v.,pp.347-350,
    11. Preliminary evaluation of transdermal delivery of melatonin in human subjects , Lee,B.J.;Parrott,K.A.;Ayres,J.W.;Sack,R.L. , Res. comm. Mol. Pathol. & Pharmacol. / v.85,pp.337-344,
    12. Pharmacological studies of sodium alginate I. Protective effet of sodium alginate on mucous membranes of upper-gastrointestinal tract , Koji,D.;Yutaka,W.;Chiaki,Y.;Mamabu,Y.;Seiji,O.;Masayuki,O.;Takashi,M. , Yakugaku Zasshi / v.101,pp.452-457,
    13. Release characteristics of ibuprofen from excipient-loaded alginate gel beads , Hwang, S,J.;Rhee,G.J.;Lee,K.M.;Oh,K.H.;Kim,C.K. , Int. J. Pharm. / v.116,pp.125-128,
    14. A comparison of the gastric retention of alginate containing tablet formulations with and without the inclusion of excipient calcium ions , Davies,N.M.;Farr,S.J.;Kellaway,L.W.;Thomas,G.T.M. , Int. J. Pharm. / v.105,pp.97-101,
    15. Enhancement of solubility and dissolution rate of poorly water-soluble naproroxen by complexation with 2-hydroxypropyl-β-cyclodextrin , Lee,B.J.;Lee,J.R. , Arch. Pharm. Res. / v.18,pp.22-26,
    16. Alginate beads as controlled release polymeric drug delivery system , Hwang,S.J.;Rhee,G.J.;Jo,H.B.;Lee,K.M.;Kim,C.K. , J. Kor. Pharm. Sci. / v.23,pp.19-26,
    17. Calcium-induced gelation of alginic acid and pH-sensitive reswelling of dried gels , Yotsuyanagi,T.;Ohkubo,T.;Ohhashi,T.;Ikeda,K. , Chem.Pharm.Bull. / v.35,pp.1555-1563,
    18. Preparation and release characteristics of polymer-reinforced and coated alginate beads , Lee,B.J.;Min,G.H. , Arch. Pharm. Res. / v.18,pp.183-188,

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  • Min, Geun-Hong (1)

  • 김태완 (8)

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