Injectable Liposomal Formulations: Systematic Analysis for Regulatory Purposes

Abstract

Background: Among the drug delivery systems, liposomes stand out for their biocompatible and biodegradable characteristics and high versatility. There are many marketed liposomal drug products, most of them injectables. From a regulatory perspective, some documents were published by FDA and EMA, but a systematic analysis of the factors influencing efficacy, toxicity and stability of injectable liposomal drug products has not yet been carried out in order to identify regulatory relevant items. Method: We use cause and effect diagrams (Ishikawa) to provide knowledge for regulatory action and to support the development of regulation or guidelines containing specific requirements for injectable liposomal drug products, especially with regard to their quality control and stability. Result: It was possible to identify the critical quality attributes to the efficacy, safety and stability of injectable liposomal drug products, and some of the tests to be considered in their characterization, quality control and stability. Some important aspects of the main analytical methods used for particle size and electric surface charge determination were described. An analysis of some specific topics related to Good Manufacturing Practices of injectable liposomal drug products is presented. Conclusion: The documents published by FDA and EMA do not include all the items that need to be assessed for injectable liposomal drug products quality, and do not address analytical methods for quality attributes evaluation. It is urgent to establish regulatory requirements covering these products. Keywords: Analytical methods, characterization, efficacy, liposomes, regulation, stability, toxicity.