Dissolving microneedle patches for transdermal delivery of paroxetine: studies and its PBPK modeling.

Background: Paroxetine HCl (PRX-HCl), an antidepressant, has poor water solubility and low oral bioavailability with 50% being metabolized in the liver. The oral formulations have multiple side effects. The present work aimed to develop dissolving microneedle patches (MNPs) of PRX-HCl to resolve low bioavailability and side effect issues while achieving enhanced transdermal delivery.

Materials And Methods: Three silicone templates of varying dimensions were used to fabricate 27 blank and nine PRX-HCl MNPs with PVP and PVA through mold casting method. MNPs were evaluated for physicochemical properties, . The optimized MNP was further analyzed for FTIR, DSC, skin penetration, PBPK modeling, and stability.

Results: MNPs from the optimized formulation successfully created microchannels in rat skin, demonstrated higher permeation than control MNPs with a flux of 146.18 ± 13.42 µg/cm/h, presented a decrease in lag phase and an increase in drug plasma C and AUC compared to PAXIL CR 12.5 mg oral, and showed higher stability in the room and refrigerator conditions.

Conclusion: The prepared MNPs were stable and can deliver PRX-HCl sufficiently across skin barrier with enhanced bioavailability compared to oral administration at similar doses and thus be a better alternative to already available delivery systems for PRX-HCl.