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

Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile

“…The results of permeability studies of DH from the tested samples across the Calu-3 cell monolayer are given in Table 4. The P app value of the DH from the solution in HBSS/HEPES (pH 7.0) (DH concentration 0.25 mg mL −1 ; P app = 3.38 × 10 −5 cm s −1 ) evaluated in this study is in line with the previously obtained P app value for the DH solution in HBSS-Ca 2+ /HEPES (pH = 6.0) (DH concentration 0.008 mg mL −1 ; osmolality 321 ± 1 mOsm/kg; P app = 3.59 × 10 −5 cm s −1 ) using the same cell model [12]. The attenuation factor was calculated as the ratio between the P app value of the LF or DH solution in hyperosmolar HBSS/HEPES (pH = 7.0) and the P app value of the DH solution in HBSS/HEPES (pH = 7.0).…”

“…It can be assumed that breathing and airflow steer the formulation from its original direction to the turbinate region and, as a result, a smaller fraction of the drug is deposited in the olfactory region. From the patient’s perspective, a ‘breath hold’ condition is preferred during the administration: less coordination between breathing and actuation leads to lower variability, and thus patient adherence to the therapy is facilitated [ 12 , 32 ].…”

“…The attenuation factor was calculated as the ratio between the P app value of the LF or the DH solution in the hyperosmolar HBSS/HEPES (pH = 7.0) and the P app value of the DH solution in the HBSS/HEPES (pH = 7.0) [ 12 ].…”

“…Recently, our research team pioneered and extensively investigated the issue of coupling formulation and administration parameters employing the quality-by-design (QbD) approach to optimise the nasal deposition pattern in vitro in relation to the specific disease in adults [ 10 ]. Such an approach has been shown to hold great promise in promoting targeted nasal drug delivery [ 11 , 12 ].…”

“…Finally, the results on the nasal deposition of the leading in situ gelling formulation will be compared with the results obtained previously with optimised donepezil powder formulation [ 12 ] to account for the differences in accessibility of the olfactory region using two distinct formulation approaches.…”