Proceedings 2021, 78, 49. https://doi.org/10.3390/IECP2020-08661 www.mdpi.com/journal/proceedings Proceedings How Could QbD Address the R&D Challenges of ‘Nose-To-Brain’ Liposomal Resveratrol Formulations? † Zsófia Németh, Edina Pallagi, Dorina Gabriella Dobó and Ildikó Csóka * Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary; nemeth.zsofia@szte.hu (Z.N.); pallagi.edina@szte.hu (E.P.); dobo.dorina.gabrialla@szte.hu (D.G.D.) * Correspondence: csoka.ildiko@szte.hu; Tel.: +36-62-546-115 † Presented at the 1st International Electronic Conference on Pharmaceutics, 1–15 December 2020; Available online: https://iecp2020.sciforum.net/. Abstract: Trans-resveratrol, due to its antioxidant property, has the potential to be successfully ap- plied in the prevention and the treatment of neurological disorders (Parkinson’s and Alzheimer’s disease). Nevertheless, its traditional administration (intravenous, oral) and bioavailability are lim- ited 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 (RA), 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 defi- nition 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 modifica- tion), as well as the production process (temperature, oxidation and light protection) were identi- fied; subsequently, an RA-based liposome preparation process was described. The formulation pro- cedures 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. Keywords: liposome; resveratrol; nose-to-brain; Quality by Design; risk assessment 1. Introduction Trans-resveratrol (RSV) (3,4′,5-trihydroxy stilbene) (Figure 1) is a polyphenolic phy- toalexin compound that has been studied in a broader scale to prevent and treat diseases due to its several biological effects [1]. Many beneficial properties of the compound are known, such as antioxidant, antidiabetic, cardioprotective, immunomodulatory, anti- tumor, antihypertensive, anti-inflammatory, platelet aggregation inhibitor, anti-ageing and anti-obesity effects [1–3]. RSV effectively attacks the extracellular reactive oxygen spe- cies (ROS) and is, therefore, a potent antioxidant compound. The use of RSV is recom- mended to prevent and treat chronic diseases such as metabolic disorders, tumours and neurodegenerative disorders [1,4]. It has been demonstrated in a rat model that RSV-con- taining lipid-based nanocarrier systems ameliorate the β-amyloid plaques that mediate memory impairments in Alzheimer’s disease [5]. The outcome of the RSV therapy is the result of different processes (reduction of NF-κB (nuclear factor-kappa B)), inhibition of Citation: Németh, Z.; Pallagi, E.; Dobó, D.G.; Csóka, I. How Could QbD Address the R&D Challenges of ‘Nose-To-Brain’ Liposomal Resveratrol Formulations? Proceedings 2021, 78, 49. https:// doi.org/10.3390/IECP2020-08661 Published: 1 December 2020 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (http://cre- ativecommons.org/licenses/by/4.0/).