Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
J Pharm Pharmacol. 2012 Jul;64(7):969-85. doi: 10.1111/j.2042-7158.2011.01439.x. Epub 2012 Feb 7.
Dissolution testing is a powerful tool for the characterization of dosage form performance in vitro under standardized conditions. In spite of the increasing number of parenterally administered medicinal products, currently there are no compendial dissolution test methods designed especially for these types of dosage forms. In addition to classical drug delivery systems, drug/device combination products, such as drug-eluting stents, are being used increasingly.
This review describes the current methods that are used most often for in-vitro dissolution testing of parenteral dosage forms, i.e. the 'sample and separate' methods, the 'dialysis' methods, and the 'flow-through' methods, with a special emphasis on whether these methods can be used for drug-eluting stent testing. In the light of current regulatory requirements and with the exploding costs of preclinical and clinical development, test systems that include biorelevant parameters and are predictive of in-vivo performance are increasingly important. Published attempts to take biorelevant conditions into consideration in the design of dissolution test apparatus developed for parenteral dosage forms, including a method that was designed to emulate the embedding and flow-conditions at the site of stent implantation, have been outlined in this review.
In spite of the large quantity of highly potent controlled release parenteral products marketed today, there is still a lack of suitable methods for in vitro dissolution testing for these dosage forms especially with regard to biorelevant testing conditions. For dosage forms implanted into tissues it seems of major importance to reproduce the transport forces which are predominant in vivo (diffusive versus convective) in the in-vitro experimental setup.
溶解测试是一种强大的工具，可在标准化条件下对剂型的体外性能进行表征。尽管越来越多的药物是通过注射给药，但目前还没有专门为这些类型的剂型设计的药典溶解测试方法。除了传统的药物递送系统外，药物/器械组合产品，如药物洗脱支架，也越来越多地被使用。
本文描述了目前最常用于注射剂型体外溶解测试的方法，即“取样分离”法、“透析”法和“流动-through”法，并特别强调了这些方法是否可用于药物洗脱支架的测试。鉴于当前的监管要求以及临床前和临床开发成本的不断增加，越来越需要包含生物相关参数并能预测体内性能的测试系统。本文概述了为注射剂型设计的溶解测试装置中考虑生物相关条件的尝试，包括旨在模拟支架植入部位的嵌入和流动条件的方法。
尽管目前市场上有大量的高活性控释注射产品，但对于这些剂型的体外溶解测试，尤其是对于生物相关测试条件，仍然缺乏合适的方法。对于植入组织的剂型，在体外实验装置中重现体内主要的传输力（扩散与对流）似乎非常重要。
