Larsen Claus, Ostergaard Jesper, Larsen Susan W, Jensen Henrik, Jacobsen Stine, Lindegaard Casper, Andersen Pia H
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
J Pharm Sci. 2008 Nov;97(11):4622-54. doi: 10.1002/jps.21346.
The joint cavity constitutes a discrete anatomical compartment that allows for local drug action after intra-articular injection. Drug delivery systems providing local prolonged drug action are warranted in the management of postoperative pain and not least arthritic disorders such as osteoarthritis. The present review surveys various themes related to the accomplishment of the correct timing of the events leading to optimal drug action in the joint space over a desired time period. This includes a brief account on (patho)physiological conditions and novel potential drug targets (and their location within the synovial space). Particular emphasis is paid to (i) the potential feasibility of various depot formulation principles for the intra-articular route of administration including their manufacture, drug release characteristics and in vivo fate, and (ii) how release, mass transfer and equilibrium processes may affect the intra-articular residence time and concentration of the active species at the ultimate receptor site.
关节腔构成一个独立的解剖腔室,关节腔内注射后可实现局部药物作用。在术后疼痛尤其是骨关节炎等关节炎性疾病的治疗中,需要能提供局部长效药物作用的给药系统。本综述探讨了与在期望时间段内实现导致关节腔内最佳药物作用的事件的正确时间安排相关的各种主题。这包括对(病理)生理状况和新的潜在药物靶点(及其在滑膜腔内的位置)的简要介绍。特别强调了:(i)各种用于关节内给药途径的长效制剂原则的潜在可行性,包括其制造、药物释放特性和体内转归;(ii)释放、传质和平衡过程如何影响活性物质在最终受体部位的关节内停留时间和浓度。