Sustained-Release Delivery Systems, II: In Vitro Dissolution of 4,4′-Sulfonylbisbenzamine (Dapsone)—N-Dodecanoyl-4,4′-sulfonylbisbenzamine Comelts

An approach under investigation in our laboratory is the development of slowly dissolving particles containing an active drug, mixed or coated with a less soluble derivative or derivatives, that may hydrolyze back to the active drug following solution. Such particles have potential for sustained release by a number of routes of administration, including intramuscular injection. In the present work, the in vitro dissolution of particles of 4,4′-sulfonylbisbenzamine (dapsone) (1) and various comelts of 4,4′-sulfonylbisbenzamine (dapsone) (1) and N-dodecanoyl-4,4′-sulfonylbisbenzamine (the monolauryl derivative of dapsone) (3) was studied using a continuous flow-through cell under laminar flow conditions. Dissolution of particles of dapsone showed a biphasic pattern when plotted according to the Hixson—Crowell cube root equation. Dissolution rates of dapsone (1) from the comelts were found to correlate with the physical state of 1 in the solid binary dispersion. Comelts of 1:3 with a content higher than 36.5% w/w 1 (the eutectic mixture) had initial rates of dissolution which appeared to be dependent on the porosity of the particles. However, once this initial phase passed, the total amount dissolved increased as the amount of noneutectic 1-rich solid solution in the comelt increased. This suggests that 1 in the eutectic mixture has a slower dissolution rate than when present in the noneutectic, or excess 1-rich solid solution form. The comelts with a content of dapsone at or below the eutectic mixture dissolved more slowly and their dissolution rates were less dependent on concentration of 1. The mechanism of release of 1 from 1:3 comelts appeared to be matrix diffusion-controlled.