Calcium Sulfate as a Delivery Vehicle for Simvastatin

Objective: To investigate use of calcium sulfate as a vehicle for localized delivery of simvastatin, which is documented to enhance bone formation. Methods: Calcium sulfate hemihydrate (CS) was used to fabricate hemispherical samples having diameter of 6 mm and height of 4 mm. Simvastatin (Sim) was used either as-received or following hydrolysis to the beta-hydroxyacid form. CS was loaded with Sim by either adsorption onto preset hemispheres or mixing into CS powder prior to forming a slurry and placing it in molds. Different amounts of Sim were loaded onto/into samples to modulate release profiles. Loaded samples were incubated in physiological saline at 37ºC, and supernatant was collected every 1-3 days. The amount of released Sim was determined by UV spectroscopy. Results: Whereas adsorption of Sim on CS had no noticeable effect on the samples' initial physical properties, incorporation of larger amounts (>0.1wt%) weakened materials to the extent that they disintegrated overnight in saline. With lower loadings, however, integrity was retained and controlled release was obtained. For CS mixed with Sim, linear release of 0.8-1.2µg Sim per day was observed following a small, loading-dependent, initial burst of 1.5-4µg. Later release could not be further increased, because it is dependent on erosion of the CS substrates. For CS adsorbed with Sim, nonlinear profiles were found, with a much larger initial burst of 60-140µg. The higher the concentration of Sim in the adsorbing solution, the larger the initial burst. Conclusion: CS can serve as a vehicle for localized release of Sim for the purpose of repairing localized bone defects. Although extended, linear release behavior was found for Sim incorporated into CS, the slow rate of release is unlikely to deliver effective doses of the drug. Use of the easier adsorption method provides a short duration of release but at more pharmacologically relevant doses.