engleski

Biopharmaceutical properties of mucoadhesive powder platform for donepezil nasal delivery

Background Donepezil hydrochloride (DH) is commonly used for the treatment of symptoms of Alzheimer’s disease as an oral dosage form (1). Nasal DH administration provides the potential for direct and efficient DH delivery to the central nervous system, while reducing its systemic side effects (2). Purpose The aim of this study is to investigate the potential of spray dried DH loaded chitosan/mannitol microspheres for nasal DH delivery by relevant biopharmaceutical in vitro and ex vivo characterisation. Methods DH loaded chitosan/mannitol microspheres were characterised in terms of DH in vitro release profile, ex vivo mucoadhesiveness using porcine nasal mucosa, in vitro biocompatibility with Calu- 3 cells and DH permeability across Calu-3 cell monolayer. DH loaded chitosan microspheres, pure DH powder and/or pure mannitol were used as controls where appropriate. Results Both, chitosan and chitosan/mannitol microspheres provided prolonged DH release in comparison to pure DH powder. DH loaded chitosan/mannitol microspheres showed prominent mucoadhesive properties. Calu-3 cells exposed to microsphere suspensions prepared at chitosan concentration 10– 30 μg/mL retained viability above 90% in relation to negative control. The Papp values of DH from chitosan/mannitol and chitosan microspheres showed 1.16 and 1.30-fold higher DH permeation in relation to DH solution, respectively. Conclusion Formulating DH as chitosan/mannitol microspheres resulted in prolonged drug release, increased mucoadhesiveness and enhanced drug permeation across Calu-3 monolayer. Results on in vitro biocompatibility confirmed the formulation potential for safe and efficient DH nasal delivery.

nasal drug delivery ; spray-dried microparticles ; chitosan ; donepezil ; biopharmaceutical properties

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