How Could QbD Address the R&D Challenges of ‘Nose-To-Brain’ Liposomal Resveratrol Formulations?

Abstract

Trans-resveratrol, due to its antioxidant property, has the potential to be successfully applied in the prevention and the treatment of neurological disorders (Parkinson's and Alzheimer's disease). Nevertheless, its traditional administration (intravenous, oral) and bioavailability are limited by its physical-chemical characteristics (solubility, chemical instability, sensitivity to heat, UV-light and pH). The 'nose-to-brain' application, as an alternate administration route, represents a way to reach the brain without the limitations of the blood-brain barrier, while the use of nano-sized drug delivery systems, like the liposomes, can overcome the developmental and therapeutic issues of the formulations. This research paper shows the application of Risk Assessment, the key element of the Quality by Design mindset, in the development of a liposomal resveratrol-containing formulation with brain target and nasal administration. The study intends to demonstrate the definition of the quality target product profile, the selection of the critical factors, and the application of the RA to get a detailed view on the critical parts of the development process. On these terms, the factors with the most significant impact on the product quality among the critical material attributes (phospholipids, active pharmaceutical ingredient (API) content, cholesterol ratio, surface modification), furthermore the production process (temperature, oxidation and light protection) were identified; subsequently, an RA-based liposome preparation process was described. The formulation procedures of 'nose-to-brain' liposomal systems loaded with drugs with many limiting factors meet several risks; however, the adaption of the QbD tools helps to focus on the aimed final product quality and achieve effective experimental designs.