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 o f droplets of an alginate solution containing dispersed theophylline, followed by air-drying of the gel beads. The effect of various product ion factors on the size, composition and drug release properties was i nvestigated 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 concen tration used for gelation also appeared to have a significant influenc e. 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 o f drug also affected the moisture content. The calcium and alginate co ncentrations, the gelling time, the drug addition and the alginate G c ontent affected the drug release rate in water. An increase in the lev el of all these factors caused a retardation in release. Several syner gistic two-factor interactions were also observed.