Development and Optimization of Memantine-Loaded Nanostructured Lipid Carriers Using a Quality by Design Approach

Background: Nanostructured lipid carriers (NLCs) offer a promising strategy to enhance the delivery of memantine by improving drug encapsulation and providing controlled release. This study aimed to develop and optimize memantine-loaded NLCs using a Quality by Design (QbD) approach to achieve a robust formulation with desirable physicochemical characteristics. Methods: Memantine-loaded NLCs were prepared by hot homogenization followed by probe sonication. A Box–Behnken Design was employed to evaluate the influence of critical material attributes, including solid lipid concentration, liquid lipid concentration, and surfactant concentration, on particle size, entrapment efficiency, and polydispersity index. The optimized formulation was characterized for particle size, zeta potential, morphology, crystallinity, drug encapsulation, and in vitro drug release. Results: Statistical optimization identified significant formulation variables affecting the critical quality attributes. The optimized NLCs exhibited nanoscale particle size, high entrapment efficiency, narrow size distribution, and sustained drug release with satisfactory physicochemical stability. Conclusion: The QbD-based optimization successfully produced a robust memantine-loaded NLC formulation suitable for further incorporation into a transdermal drug delivery system for Alzheimer's disease management.