Department of Pharmaceutics, Semmelweis University, 7-9 Hogyes E. Street, H-1092, Budapest, Hungary.
AAPS PharmSciTech. 2010 Mar;11(1):285-93. doi: 10.1208/s12249-009-9368-1. Epub 2010 Feb 24.
An intravenous solution is a dosage forms intended for administration into the bloodstream. This route is the most rapid and the most bioavailable method of getting drugs into systemic circulation, and therefore it is also the most liable to cause adverse effects. In order to reduce the possibility of side effects and to ensure adequate clinical dosage of the formulation, the primarily formulated composition should be optimized. It is also important that the composition should retain its therapeutic effectiveness and safety throughout the shelf-life of the product. This paper focuses on the optimization and stability testing of a parenteral solution containing miconazole and ketoconazole solubilized with a ternary solvent system as model drugs. Optimization of the solvent system was performed based on assessing the risk/benefit ratio of the composition and its properties upon dilution. Stability tests were conducted based on the EMEA (European Medicines Agency) "guideline on stability testing: stability testing of existing active substances and related finished products". Experiments show that both the amount of co-solvent and surface active agent of the solvent system could substantially be reduced, while still maintaining adequate solubilizing power. It is also shown that the choice of various containers affects the stability of the compositions. It was concluded that by assessing the risk/benefit ratio of solubilizing power versus toxicity, the concentration of excipients could be considerably decreased while still showing a powerful solubilizing effect. It was also shown that a pharmaceutically acceptable shelf-life could be assigned to the composition, indicating good long-term stability.
静脉注射液是一种旨在注入血液的剂型。这种途径是将药物快速而最大限度地输送到全身循环的方法，因此也是最容易引起不良反应的方法。为了降低副作用的可能性，并确保制剂的足够临床剂量，主要的配方组成应进行优化。同样重要的是，在产品的保质期内，制剂应保持其治疗效果和安全性。本文专注于含有咪康唑和酮康唑的肠外溶液的优化和稳定性测试，这些药物用三元溶剂系统溶解作为模型药物。基于评估组成物及其稀释后性质的风险/效益比，对溶剂系统进行了优化。稳定性测试基于 EMEA（欧洲药品管理局）“稳定性测试指南：现有活性物质和相关成品的稳定性测试”进行。实验表明，溶剂系统的共溶剂和表面活性剂的量都可以大大减少，同时仍保持足够的溶解能力。还表明，各种容器的选择会影响组合物的稳定性。结论是，通过评估溶解能力与毒性的风险/效益比，可以在仍显示出强大溶解效果的同时，大大降低赋形剂的浓度。还表明可以为该组合物分配可接受的有效期，表明其具有良好的长期稳定性。
