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

Abstract

Liposomal formulation development is a challenging process. Certain factors have a critical influence on the characteristics of the liposomes, and even the relevant properties can vary based on the predefined interests of the research. In this paper, a Quality by Design-guided and Risk Assessment (RA)-based study was performed to determine the Critical Material Attributes and the Critical Process Parameters of an “intermediate” active pharmaceutical ingredient-free liposome formulation prepared via the thin-film hydration method, collect the Critical Quality Attributes of the future carrier system and show the process of narrowing a general initial RA for a specific case. The theoretical liposome design was proved through experimental models. The investigated critical factors covered the working temperature, the ratio between the wall-forming agents (phosphatidylcholine and cholesterol), the PEGylated phospholipid content (DPPE-PEG2000), the type of the hydration media (saline or phosphate-buffered saline solutions) and the cryoprotectants (glucose, sorbitol or trehalose). The characterisation results (size, surface charge, thermodynamic behaviours, formed structure and bonds) of the prepared liposomes supported the outcomes of the updated RA. The findings can be used as a basis for a particular study with specified circumstances.

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives

“…These values were significantly more negative (p < 0.01) in the case of the DCP-PBS pH 5.6 (−36.7 ± 3.3 mV) sample than in those made with the saline solution (−19.8 ± 2.0 mV) or the PBS pH 7.4 made ones (−19.8 ± 2.0 mV). These results prove the relation between the ionic strength of the hydration media and the zeta potential value of the produced liposomes: the absolute zeta potential value increases with the ionic strength [22,75]. The highest absolute zeta potentials were measured in the samples made with PBS pH 5.6 (ionic strength: 0.40 M).…”

“…The properties of the liposomes made via thin-film hydration are influenced by the presence and quality of the API, the type and proportion of the wall-forming compounds, the quality of the cryoprotectant and the hydration media, and they are affected by the applied temperature, pressure and settings of the filtration [21]. Based on the results, recommendations are available on the QTPP of an API-free liposomal carrier system [22]; however, the zeta potential needs to be investigated to characterise liposome stability further. The influencing factors on liposome properties as results of the RAs are summarised in Figure 1.…”

Nano–Liposomes Double Loaded with Curcumin and Tetrandrine: Preparation, Characterization, Hepatotoxicity and Anti–Tumor Effects

“…Therefore, modifiers are selected to protect the stability of liposomes [ 33 ]. DP is a widely used stabilizer in liposomes [ 34 ]. The experimental results showed that the addition of DP could not only significantly improve the particle size distribution of CT–DP–Lip but also significantly improve the EE and LC of CUR and TET in liposomes.…”

Central Composite Design (CCD) for the Optimisation of Ethosomal Gel Formulation of Punica granatum Extract: In Vitro and In Vivo Evaluations

“…Characterisation of the formulated gels in terms of parameters, zeta potential, particle size, and vesicle size was performed. The results indicated that the developed formulation was good and having acceptable physicochemical properties in terms of pH, viscosity, spreadability, and absence of grittiness [ 24 ]. Furthermore, the study was performed to evaluate the ethosome gel formulation in terms of viscosity, spreadability, and pH.…”