The College of Pharmacy discussed the PhD dissertation entitled “Flunarizine Loaded Spanlastic as Potential Nose to Brain In-Situ Gel: Preparation and Invitro/Invivo Study” by the student Mahmood A. Haiss and the supervisor, Professor Dr. Shaimaa N. Abdulhammid, at the Pharmaceutics Department.
The study aimed to design, optimize, and evaluate flexible nanovesicles loaded with flunarizine (FNZ) using a systematic framework based on the Quality by Design approach. Multiple analytical tools were integrated, including Ishikawa cause-and-effect analysis, Plackett–Burman design, and response surface methodology, with the objective of enhancing brain targeting and improving the bioavailability of flunarizine via intranasal administration.
The study included the use of an Ishikawa (fishbone) diagram to identify potential risk factors that may influence the critical quality attributes of FNZ-loaded nanovesicles (FNZ-SNVs). A Plackett–Burman experimental design was applied to evaluate the effects of eight formulation and process variables, which influence vesicle size, zeta potential, vesicle deformability, and encapsulation efficiency. Based on Pareto chart analysis, three critical factors were identified: the type of vesicle-forming component (Span 60), the type of edge activator (Tween 60), and ultrasonication duration. These factors were further optimized at three levels using formulation design to minimize vesicle size and enhance both encapsulation efficiency and vesicle deformability of FNZ-SNVs.
The results showed that the optimized FNZ-SNVs formulation, composed of Span 60 and Tween 60 in a ratio of 7:3 and subjected to ultrasonication for 3 minutes, demonstrated superior physicochemical properties. The vesicle size was 95.53 nm, entrapment efficiency reached 84.38%, relative deformability was 15.71, and dissolution efficiency was 90.2%. Subsequently, the optimized formulation was incorporated into an in-situ gel (IG) and further evaluated in vivo. The results revealed that intranasal delivery of FNZ-SIG achieved significantly higher brain targeting compared to intravenous FNZ solution, with a remarkably high drug targeting index (DTI) of 2.52 and drug targeting efficiency (DTE%) of 252.3%.
The study recommends the adoption of the Quality by Design (QbD) approach as an effective strategy for developing advanced brain-targeted drug delivery systems, particularly via the intranasal route. Furthermore, the findings support the use of flexible nanovesicles as promising carriers to enhance bioavailability and improve central nervous system targeting, paving the way for more efficient and safer future therapeutic applications.
