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.

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

“…The dissolution profiles of all the tablets were curve-fitted to mathematical drug release models ( Table 5 ). The HPMC-AS HG release profiles fit well with the Higuchi model, whereas there is a declining trend of correlation to the Higuchi model observed in HPMC-AS MG and HPMC-AS LG which is understandable since the Higuchi model considers dissolution, as well as shape change of the system insignificant and, is more focused on the release via diffusion [ 49 ].…”

“…It can be seen that all the profiles fit well with the zero-order release kinetics ( Table 5 ). This is because the drug release is not due to the immediate disaggregation of the dosage form as seen in immediate release or orally disintegrating tablets, but rather due to the slow release of the drug [ 49 ]. This slow-release can be attributed to the sink conditions maintained throughout the study and the inherent properties of ASDs where the drug releases occur by slow surface dissolution of the tablets.…”

Curcumin-Loaded Nanoemulsion for Better Cellular Permeation

“…The Korsmeyer-Peppas model was used to further explain the mechanism of curcumin release. The release was found to follow Fickian diffusion as the release exponent was 0.3 (<0.5) [18]. This means that curcumin diffused at a comparatively slower rate, as the diffusion time was longer based on the square root kinetic of the Korsmeyer-Peppas model.…”

Tunable Release of Curcumin with an In Silico-Supported Approach from Mixtures of Highly Porous PLGA Microparticles

“…Mathematical models represent a fundamental tool to optimally design new pharmaceutical systems, to study drug formulations and to evaluate in vitro and in vivo releases [23][24][25][26]. They rely on the model fitting of experimental data and equations and they enable a quantitative interpretation of the values obtained from a drug release assay [27].…”