CALCIUM ALGINATE MATRICES FOR ORAL MULTIPLE-UNIT ADMINISTRATION .2. EFFECT OF PROCESS AND FORMULATION FACTORS ON MATRIX PROPERTIES

Small calcium alginate matrices were prepared by ionotropic gelation of droplets of an alginate solution containing dispersed theophylline, followed by air-drying of the gel beads. The effect of various production factors on the size, composition and drug release properties was investigated in two separate studies. A 2(3) factorial design and a 2V5-1 fractional factorial design were applied. The size of the matrices was controlled mainly by the coaxial airstream applied during droplet production. However, the alginate concentration and the calcium concentration used for gelation also appeared to have a significant influence. The latter two factors, together with the amount of drug dispersed, determined the matrix drug content. The calcium concentration and the amount of drug affected matrix calcium content the most. The amount of drug also affected the moisture content. The calcium and alginate concentrations, the gelling time, the drug addition and the alginate G content affected the drug release rate in water. An increase in the level of all these factors caused a retardation in release. Several synergistic two-factor interactions were also observed.