Dissolving microneedle patches for transdermal delivery of paroxetine: in-vitro, ex-vivo 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, in-vitro release, and ex-vivo permeation. The optimized MNP was further analyzed for FTIR, DSC, skin penetration, in-silico 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/cm2/h, presented a decrease in lag phase and an increase in drug plasma Cmax 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.