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

Abstract

The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa. The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box–Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and −33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 μg/cm2) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases.

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

“…The following steps of the QbD method are the application of the Control Strategy and the planning of the Continuous Improvement, which have relevance from the perspective of the pharmaceutical industry. The QbD-, and RA-based development and screening have several advantages; thus, the experiments could be more effective in practice, and it can be especially useful in the early pharmaceutical developments of complex or sensitive drugs or systems with special considerations [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Development and Characterization of n-Propyl Gallate Encapsulated Solid Lipid Nanoparticles-Loaded Hydrogel for Intranasal Delivery

“…In our previous work we had already investigated the formulation possibilities of PG-loaded liposomes coated with HA [ 41 ], as PG has advantageous effects (anti-inflammatory, antioxidant and anticancer activity) in the treatment of brain tumors, e.g., glioblastoma multiforme. As PG is a water-insoluble compound, loading it into a nanocarrier can enhance its water solubility and drug release profile in different administration routes.…”

“…For the calibration line, the linear regression was 0.998. The quantification limit (LOQ) and detection (LOD) of PG were 63 ppm and 21 ppm, respectively [ 41 , 59 ].…”

“…For the calibration line, the linear regression was 0.998. The quantification limit (LOQ) and detection (LOD) of PG were 63 ppm and 21 ppm, respectively [41,59] PG-SLN HGs containing HA in different concentrations (0.5, 1, 2 and 3% w/v) were evaluated apparently for grittiness and uniformity. The pH of HGs was measured directly by dipping pH meter (WTW ® inoLab ® pH 7110 laboratory pH tester, Thermo Fisher Scientific, Budapest, Hungary).…”

Design and development of topical liposomal formulations in a regulatory perspective

“…As other complex formulations, small changes in the critical quality attributes (CQA) have a substantial impact on the performance of in vivo and, therefore, an in-depth evaluation should be mandatory for driving the pharmaceutical development based on the target product profile (TPP) of the finished product [ 22 ]. Thus, as above mentioned, deep characterization of chemical features of excipients and their possible interactions with the drug is required for quality purposes in the definition of formulation space which can be rationalized with the help of Quality-by-Design (QbD) [ 29 , 30 ].…”