Evaluation of the release kinetics of a pharmacologically active substance from model intra-articular implants replacing the cruciate ligaments of the knee

Abstract

Implants are readily applied as a convenient method of therapy. There is great interest in the prolonged release of active substances from implants. The objective of this work was to evaluate the dissolution kinetics of steroidal anti-inflammatory preparation (SAP) released from novel implants, and to test the influence of the technology on SAP release kinetics. The proposed long-acting preparations may overcome difficulties resulting from repeated injections and often visits to ambulatory clinic, as the stabilizing function of the artificial ligament would be enriched with pharmacological activity. The potential advantages provided by the new coatings of knee implants include the continuous, sustained, and prolonged release of an active substance. The study was carried out using a modified United States Pharmacopoeia (USP) apparatus 4. The amount of SAP was measured spectroscopically. It was revealed that the transport of the drug was mainly a diffusion process. The drug release kinetics was analyzed using zero-, first-, and second-order kinetics as well as Korsmeyer-Peppas, Higuchi, and Hixon-Crowell models. The highest values of the release rate constants were k0 = (7.49 ± 0.05) × 10-5 mg × min-1, k1 = (6.93 ± 0.05) × 10-6 min-1, and k2 = (7.70 ± 0.05) × 10-7 mg-1 × min-1 as calculated according to zero-, first-, and second-order kinetics equations, respectively. The values of the rate constants obtained for the slowest process were k0 = (3.63 ± 0.06) × 10-5 mg × min-1, k1 = (2.50 ± 0.03) × 10-6 min-1, and k2 = (2.80 ± 0.03) × 10-7 mg-1 × min-1. They may suggest the possibility of sustained release of betamethasone from the system. Due to the statistical analysis, differences were observed between most of the studied implants. Incubation, temperature, time of stabilization of layers, and the method of SAP deposition on the matrix affected the drug release.