Sustained-Release Delivery Systems, I: Phase Diagram Studies of Dapsone and Selected Derivatives

In order to develop slowly dissolving particles containing the antileprotic drug dapsone (4, 4′-sulfonylbisbenzamine, 1) that would be suitable for a sustained-release intramuscular injection, the dilauryl (2) and monolauryl (3) derivatives of dapsone, N,N'-didodecanoyl-4, 4′-sulfonylbisbenzamine and N-dodecanoyl-4, 4′-sulfonylbisbenzamine, respectively, were studied for their ability to form solid dispersions with the parent compound. The 1:2 binary phase diagram showed these two compounds were partially miscible in the liquid state, leading to the coexistence of a monotectic and a eutectic system in the phase diagram. The 1:3 phase diagram showed that these compounds were completely miscible in the liquid state and formed discontinuous solid solutions in the solid state. At a cooling rate of 2.5°C min−1, eutectic mixtures lying on the dapsone side of the eutectic point formed glass solutions. Taken as a whole, the results demonstrate that the molecular interactions between 1 and 3 are stronger than those between 1 and 2. Accordingly, 3 would appear to be the better carrier for reducing the rate of dissolution of dapsone from a solid dispersion.