In vitro and in vivo dapsone release from hydroxyapatite reservoirs

Dapsone is a drug which is administered orally, on a daily basis, for four to five years as a cure for leprosy. The major problems associated with dapsone therapy include hemolysis, methemoglobinemia and patient non-compliance. Cimetidine reduces the side effects of dapsone and increases its levels in the blood. A ceramic drug delivery system was developed to maintain therapeutic levels of dapsone for an extended period of time and to alleviate associated side effects. In vitro release of commercial dapsone tablets (100 mg) and cimetidine pellets (400 mg) from hydroxyapatite reservoirs was studied in 100 ml absolute ethanol at 37 degrees C. Hydroxyapatite (HA) reservoirs loaded with one dapsone tablet released the drug at the rate of 8.3 mg/day for nine days, after which a much slower release occurred for another three days. With a load of two dapsone tablets, the rate of release was 6.7 mg/day for four weeks. HA reservoirs loaded with one cimetidine pellet delivered the drug at a rate of 25 mg/day for sixteen days. Combining both drugs in a single reservoir did not affect their respective release rates. When implanted subcutaneously in rats, HA reservoirs loaded with one dapsone tablet appeared to be well tolerated. After nine weeks, 77 mg of dapsone had been released. These experiments showed that HA reservoirs can be used to deliver dapsone and cimetidine in vivo.