Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Eur J Pharm Sci. 2012 Feb 14;45(3):351-7. doi: 10.1016/j.ejps.2011.12.006. Epub 2011 Dec 9.
Most in vitro methods for evaluating parenteral oil based depots are focusing on intramuscular or subcutaneous injection. For intra-articular injection other mechanisms may control the overall drug release rate due to a relatively smaller interfacial area and longer transport distance of the drug substance in the oil to the oil-synovial fluid interface. In the current work, an in vitro model for testing drug release from oil solutions intended for intra-articular injection was evaluated. The release of the model drugs naproxen, piroxicam and ropivaciane from a well-defined surface area of the lipophilic solutions were followed using an in vitro model based on a modified USP II paddle apparatus with modest agitation (50rpm) of the oil formulation. By alteration of the viscosity of the oil, the oil-water interfacial area, the oil volume and the stirring efficiency of the release medium, it was shown that the drug release rate was dependent on the drug diffusivity in the oil and the degree of agitation generated in the oil vehicle. In addition, the partitioning of the drug between the oil vehicle and the release media was found to influence the release rate. In combination with an improved understanding of in vivo drug release and distribution, the present work may form a promising foundation for future in vivoin vitro correlations.
大多数评估注射用油基储库的体外方法都集中在肌肉内或皮下注射上。对于关节内注射，由于药物在油中的界面面积相对较小，药物向油-滑液界面的传输距离较长，其他机制可能会控制药物的整体释放速率。在目前的工作中，评估了一种用于测试旨在关节内注射的油溶液中药物释放的体外模型。使用基于改良的 USP II 桨式装置的体外模型，以适度的搅拌（50rpm）来跟踪亲脂性溶液中模型药物萘普生、吡罗昔康和罗哌卡因的释放。通过改变油的粘度、油水界面面积、油体积和释放介质的搅拌效率，可以证明药物释放速率取决于药物在油中的扩散系数和油载体中产生的搅拌程度。此外，药物在油载体和释放介质之间的分配也会影响释放速率。结合对体内药物释放和分布的更好理解，本工作可能为未来的体内-体外相关性研究奠定有希望的基础。
