Transmucosal Delivery of Duloxetine Hydrochloride for Prolonged Release: Preparation, in vitro, ex vivo Characteri-zation and in vitro-ex vivo Correlation

Abstract

Duloxetine hydrochloride is a selective serotonin and nor adrenaline reuptake inhibitor. It is used in the treatment of depression, diabetic peripheral neuropathic pain and in moderate to severe stress urinary incontinence in women. However, it undergoes extensive hepatic first-pass metabolism and susceptible to undergo degradation in acidic environment of stomach, which results in the poor bioavailability. The objective of the present study was to develop and evaluate the mucoadhesive buccal tablets (transmucosal delivery) of duloxetine hydrochloride with a goal of to increase the bioavailability and improve the patient compliance. Mucoadhesive buccal tablets were prepared by a wet granulation technique using mucoadhesive polymers like HPMC K4M, Carbopol 934P and PEO WSR 303. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, swelling index, drug content uniformity, in vitro drug release, in vitro bioadhesion and ex vivo permeation studies. The physicochemical properties of all the formulations were shown to be within the limits. The optimized buccal tablets AA1, AB3 and AC1 showed prolonged drug release for a period of 6 h with the Higuchi model release profile. Further, ex vivo permeation studies for optimized tablets were conducted and shown enhanced drug permeation. Therefore, these results demonstrated that the optimized buccal formulation of duloxetine hydrochloride enhances the oral bioavailability by delivered through the buccal route.

A Designer Antioxidant-Rich Tomato Soup As a Vehicle for Bioavailabilities of l-Tryptophan, Serotonin, and Melatonin: In Vitro Dissolution Study, In Vivo Rat Feeding, and iHOMA2 Predictive Modeling

“…Abbas et al reported a similar in vitro release profile using the ketotifen in neutral buffer from poly­( n -vinyl-2-pyrrolidone) hydrogel, indicating the erosion and dissolution of hydrogel. Serotonin release followed the Higuchi model, indicating release of biomolecules from an insoluble pectin gel matrix as a square root of a time-dependent process based on Fickian diffusion, and a similar model was reported by Peddapalli et al for drug release kinetics of duloxetine hydrochloride in buccal mucosa at neutral pH. Considerable release of l -tryptophan in SIB occurred within 30 min and followed the Higuchi model, and a similar release model of the same from a hydrogel into neutral phosphate buffer solution has been reported by Larrañeta et al…”

Improved Bioavailability of Ebastine through Development of Transfersomal Oral Films

“…Thus, the enhanced and extended absorption of EBT from the oral films might increase the bioavailability. Therefore, transmucosal delivery of EBT through GIT could possibly be enhanced by encapsulating it into transfersomes [ 12 ].…”

Formulation, optimization, in-vivo biodistribution studies and histopathological safety assessment of duloxetine HCl-loaded ultra-elastic nanovesicles for antidepressant effect after intranasal and transdermal delivery

“…Although DUL shows high oral absorption ( Elsenosy et al, 2020 ), variable poor bioavailability (≈ 40%) is achieved due to the extensive degradation in the acidic medium of the gastrointestinal tract and first-pass metabolism via the hepatic cytochrome P450 P1A2 ( El Sharawy et al, 2017 ; Salem et al, 2022 ). DUL, a BCS class-II drug, is considered a promising candidate for intranasal, as well as transdermal drug delivery, due to its physicochemical properties including lipophilicity (log P = 4.2) and molecular weight (330 g/mol) ( Peddapalli et al, 2018 ).…”

“…Various previous trials were conducted to overcome DUL's limitations. El Sharawy et al (2017) , and Peddapalli et al (2018) developed DUL-loaded buccal films and buccal tablets respectively. Setia et al (2013) aimed to surpass the acidic drug degradation by preparing DUL-loaded enteric coated mucoadhesive microspheres.…”