A Proposed Methodology for a Risk Assessment-Based Liposome Development Process

Abstract

The requirements of a liposomal formulation vary depending on the pharmaceutical indication, the target patient population, and the corresponding route of administration. Different preparation methods require various material attributes (MAs) (properties and characteristics of the components) and process parameters (PPs) (settings of the preparation method). The identification of the quality target product profile for a liposome-based formulation, the critical quality attributes of the liposomes, and the possible MAs and PPs that may influence the key characteristics of the vesicles facilitates pharmaceutical research. Researchers can systematise their knowledge by using the quality by design (QbD) approach. The potential factors that influence the quality of the product can be collected and studied through a risk assessment process. In this paper, the requirements of a liposome formulation prepared via the thin-film hydration preparation technique are presented; furthermore, the possible factors that have an impact on the quality of the final product and have to be considered and specified during the development of a liposomal formulation are herein identified and collected. The understanding and the application of these elements of QbD in the pharmaceutical developments help to influence the quality, the achievements, and the success of the formulated product.

An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

“…To get a high-quality product, knowledge of medical, pharmaceutical, chemical, biological and physical sciences should be used and mixed with technological experiences [ 4 ]. All this information needs to be considered, organised and evaluated to achieve a successful liposome-based formulation development [ 5 ].…”

A Systematic, Knowledge Space-Based Proposal on Quality by Design-Driven Polymeric Micelle Development

“…These are the factors that facilitate the implementation of the other QTPP elements. They can also appear as CQAs, but in the scope of regulation of nanosystems, these factors must be defined in the initial plan, as part of the basis of technological innovation lies in their regulation [ 8 , 12 ].…”

“…The thin film method is a production method based on complete solvent evaporation, where the drug and polymer system dissolved in any solvent (mixture) is recovered in the form of a thin film. It is then followed by hydration in water (or water-based buffer) and depending on the properties of the polymer, the process can also be followed by ultrasonication, mixing or even filtration, just like in the production process for liposomes [ 8 , 9 ]. Possible CPP elements and specific CMAs associated with each production method are collected in Table 4 .…”

“…On the one hand, the reason for this is to be found in the production process, as conventional production line equipment is not necessarily suitable for the production of these products besides the need of special conditions and constant control. The opportunity is there in the hands of all developers to apply this method and in the course of our research group, the existence was proven on many occasions for nanoDDSs, such as liposomes [ 8 ], polymeric micelles [ 9 ] and human serum albumin nanoparticles [ 10 ]. On the other hand, safety must also be proven, as an increase in efficacy is expected due to the advanced properties of the systems, but in the case of improperly optimized preparations, it can lead to nanotoxicity and severe side effects [ 11 , 12 ].…”

Quality-by-Design-Based Development of n-Propyl-Gallate-Loaded Hyaluronic-Acid-Coated Liposomes for Intranasal Administration

“…Besides, the structure of the final product in solid form is also crucial in connection with solubility, particularly its dissolution and absorption profile. Qbd-driven optimization of liposomes for the nasal administration route has already been successfully applied in a previous study [ 23 ].…”