Impact of the experimental conditions on drug release from parenteral depot systems: From negligible to significant

The aim of this study was to evaluate the impact of the experimental conditions on drug release measurements from parenteral depot systems. Frequently applied setups were used, including agitated and “non-agitated” flasks and tubes, flow-though cells as well as agarose gels. The bulk fluid volumes and flow rates were varied. Lipid implants (prepared by direct compression or melting & casting) as well as PLGA-based microparticles (prepared by O/W or W/O/W or S/O/W solvent extraction/evaporation methods) were studied. Theophylline, lidocaine, prilocaine, propranolol HCl, dexamethasone and ibuprofen were used as model drugs at different initial loadings. In all cases, the release medium was phosphate buffer pH 7.4, kept constant at 37 °C. Particle size analysis, SEM, X-ray diffraction, DSC analysis and mathematical modeling were applied to better understand the observed phenomena. Interestingly, the importance of the impact of the experimental conditions ranged from negligible to significant, depending on the specific type of drug delivery system and setup. Both, lipid implants as well as PLGA-based microparticles can exhibit more or less sensitive/robust drug release patterns. The observed differences in sensitivity could partially be explained in a mechanistic way, but in many cases they are not yet fully understood. A thorough understanding of the underlying drug release mechanisms can be very helpful. If the devices are poorly characterized and treated as “black boxes”, great care must be taken when drawing conclusions from in vitro drug release measurements.

Depending on the type of formulation, the experimental setup might or might not substantially affect the observed release kinetics from parenteral controlled drug delivery systems.Figure optionsDownload high-quality image (81 K)Download as PowerPoint slide