engleski

Development of sprayable in situ gelling system for nasal donepezil delivery: Preliminary formulation and deposition studies

BACKGROUND Due to disadvantages of oral administration of anti-dementia drug donepezil, nose-to-brain delivery attracts much attention as more efficient and safe route of administration (1). Nasal drug administration enables delivery to the central nervous system via olfactory nerve that innervates olfactory region of the nasal cavity. To ensure targeted delivery to the olfactory region, nasal deposition studies should be implemented in early phase of formulation development (2). PURPOSE The purpose of this study is to set the basis for the development of sprayable in situ gelling donepezil delivery system and to recognise the formulation and administration parameters with the highest impact on nasal deposition pattern. METHODS Thermosensitive chitosan (CS) based formulations for donepezil nose-to-brain delivery were prepared using CS and β-glycerophosphate as the gelling agent. In situ gelling systems were characterised in terms of rheological properties, droplet size distribution (DSD), spray cone angle (SCA) and nasal deposition pattern by using a representative 3D printed nasal cast. RESULTS Thermosensitive CS based in situ gelling donepezil formulations have been successfully prepared. Formulations showed suitable rheological characteristics and thermogelling properties. Under formulation and administration parameters employed, appropriate window of DSD and SCA was reached, resulting in targeted deposition in the olfactory region. CONCLUSION Preliminary studies revealed crucial formulation and administration parameters that resulted in suitable rheological properties and aerosol performance that paved the way for targeted nose- to-brain delivery.

donepezil ; nasal drug delivery ; in situ gel ; chitosan ; 3D printed nasal cast

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