A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery.

A novel approach was developed to improve the mechanical strength of tripolyphosphate (TPP)/chitosan beads prepared under coagulation condition at 4 degrees C in the presence of gelatin. Cross-sectional analysis indicated that the beads had a homogeneous crosslinked structure, as a result the beads were strengthened greatly (the mechanical strength increased more than ten times). Furthermore sodium alginate (a polyanion) can interact with cationic chitosan on the surface of these TPP/chitosan beads to form polyelectrolyte complex film for the improvement of the drug sustained release performances. The loading efficiency of model drugs (brilliant blue and FITC-dextran) in these beads was very high (more than 90%). Crosslinking time, TPP solution pH and other preparation factors had an effect on the drug release performance of beads. The release period of brilliant blue (a poor water soluble dye) was more than 2-months at a fairly constant rate in 0.9% NaCl, 10 mM PBS pH 7.4. However, for FITC-dextran (a water soluble polysaccharide) only 1-2 days in the same conditions. It seems that TPP/chitosan bead prepared by the novel method is a promising formulation for drug delivery.

[1]  M. Goosen,et al.  Microcapsules/Microspheres Related to Chitosan , 1995 .

[2]  M. Alonso,et al.  Novel hydrophilic chitosan‐polyethylene oxide nanoparticles as protein carriers , 1997 .

[3]  K. De Yao,et al.  Controlled release of albumin from chitosan-alginate microcapsules. , 1994, Journal of pharmaceutical sciences.

[4]  A. Sezer Controlled release of piroxicam from chitosan beads , 1995 .

[5]  T. Ohno,et al.  Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres , 1997 .

[6]  L. Illum,et al.  Chitosan and its use as a pharmaceutical excipient. , 1998, Pharmaceutical research.

[7]  R. Bodmeier,et al.  Preparation and Evaluation Of Drug-Containing Chitosan Beads , 1989 .

[8]  L. Hall,et al.  Some chemical and analytical aspects of polysaccharide modifications. III. Formation of branched-chain, soluble chitosan derivatives , 1984 .

[9]  S. Lin,et al.  Novel method for the preparation of controlled-release theophylline granules coated with a polyelectrolyte complex of sodium polyphosphate-chitosan. , 1985, Journal of pharmaceutical sciences.

[10]  Y. Murata,et al.  Preparation of chitosan-reinforced alginate gel beads — effects of chitosan on gel matrix erosion , 1993 .

[11]  Teruko Imai,et al.  Controlled release of indomethacin by chitosan-polyelectrolyte complex: optimization and in vivo/in vitro evaluation , 1993 .

[12]  S. Lin,et al.  The effects of thickness and hardness of the coating film on the drug release rate of theophylline granules coated with chitosan-sodium tripolyphosphate complex. , 1985, Chemical & pharmaceutical bulletin.

[13]  J. Akbuğa,et al.  Chitosan beads for the delivery of salmon calcitonin : preparation and release characteristics , 1996 .

[14]  Cenk Aral,et al.  Alternative approach to the preparation of chitosan beads , 1998 .

[15]  D. Knorr,et al.  Chitosan‐Alginate Complex Coacervate Capsules: Effects of Calcium Chloride, Plasticizers, and Polyelectrolytes on Mechanical Stability , 1988 .