Characterization of a diltiazem-lambda carrageenan complex.
In the present paper the interaction between lambda carrageenan, a natural sulphated polysaccharide, and diltiazem HCl, a Ca channel blocking agent, was studied. Dialysis equilibria were performed to quantify the binding capacity of lambda carrageenan for diltiazem. The relevance of the interaction to hydrophilic matrix systems was confirmed: a relationship was found between the binding capacity and the release profiles of matrix tablets containing a fixed amount of drug and different percentages of lambda carrageenan. Dialysis equilibria in buffered media showed that the interaction is quite insensitive to the pH of the medium (in the range 1.8-6.8), while it is reduced by increasing ionic strength; this behaviour is in line with the importance of ionic bonds in diltiazem-carrageenan interaction. On the basis of the calculated binding capacity, the complex was prepared, dried and milled. A preliminary characterization of the diltiazem-carrageenan complex in the solid state was effected by means of X-ray and DSC analysis. The amount of drug going into solution from the complex was not significantly affected by the pH of the medium (in the range 1.8-6.8), while it was increased by increasing ionic strength.
Bonferoni
M C
MC
Department of Pharmaceutical Chemistry, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy.
Rossi
S
S
Ferrari
F
F
Bettinetti
G P
GP
Caramella
C
C
D002121:Calcium Channel Blockers / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002351:Carrageenan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D003956:Dialysis; D004110:Diltiazem / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D012995:Solubility; D014867:Water / Q000737:chemistry
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D014867:Water; D002351:Carrageenan; D004110:Diltiazem