A quality by design (QbD) approach in pharmaceutical development of lipid-based nanosystems: A systematic review

Over the last few decades, there has been an impressive progress on developing novel drug delivery systems and targeted therapies through the use of Nanotechnology. In particular, lipid-based nanosystems attracted attention due to their interesting biological properties and potential to improve safety, stability and delivery efficiency of susceptible drugs. Despite the technological breakthroughs and multiple advantages related to the lipid-based nanosystems, concerns regarding quality, efficacy, and safety have increased along with the widespread of these drug products. The complex and heterogeneous structure that cannot be fully quantitated, characterized, or described by physicochemical analytical methods, as well as, the nonstandard manufacturing process, makes it very hardly to comply with reproducibility requirements and quality standards in their pharmaceutical development. Therefore, the application of a more holistic approach, such as Quality by Design (QbD), may be an effective way of surpassing technical and quality challenges. QbD is a systematic approach to product development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. In this way, a deeper product and process understanding will be achieved, that will lead to more robust and consistent lipid-based nanosystems. The present work aims to map and provide a basic understanding concerning the current state of implementation of the QbD approach in the pharmaceutical development of lipid-based nanosystems. The survey methodology applied relied on the thorough analysis of the existing literature and databases regarding lipidbased nanosystems already approved by the regulatory authorities. This analysis discloses the most common material attributes, process parameters, quality attributes, and other variables that are critical for the quality, efficacy, and safety of lipid-based nanosystems. It also includes a brief survey of current trends of risk assessment tools, design of experiments (DoE) methodologies, and characterization techniques applied to the development of these products. This higher level of knowledge will have a definite contribution to facilitate pharmaceutical development and the increase of the number of lipid-based nanosystems reaching the market in the future.