Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Neuroscience

Background:

• Oral donepezil for Alzheimer's disease has limitations.
• Nose-to-brain delivery offers a more efficient and safer alternative.
• Chitosan and mannitol are explored as carrier materials for drug delivery.

Purpose of the Study:

• To develop an advantageous powder platform for donepezil nose-to-brain delivery.
• To optimize the formulation and spray-drying process using a Quality by Design (QbD) approach.
• To evaluate the potential for efficient and safe brain-targeted delivery of donepezil.

Main Methods:

• Development of a chitosan and mannitol-based powder carrier matrix.
• Utilized spray-drying technology with an ultrasonic nozzle for particle size control.
• Employed a QbD approach integrating formulation, process, and administration parameters.
• Evaluated particle size, nasal deposition using a 3D-printed nasal model, mucoadhesion, drug release, and in vitro biocompatibility.

Main Results:

• Optimized spray-drying yielded free-flowing powder with particles >10 µm for nasal deposition.
• The QbD approach achieved 65.5% drug deposition in the olfactory region.
• The leading formulation demonstrated favorable swelling, mucoadhesion, drug release, and permeation enhancement.
• In vitro studies confirmed good biocompatibility and physico-chemical stability.

Conclusions:

• The developed powder platform is suitable for efficient and safe donepezil nose-to-brain delivery.
• The QbD-guided spray-drying process effectively optimized particle characteristics for nasal administration.
• Further in vivo studies are warranted to validate the nose-to-brain delivery concept.