The aim of this investigation was to develop receiver and extraction fluids, and subsequently validate an analytical method to quantify the permeation and penetration of flurbiprofen into human pharynx tissue using a Franz diffusion cell. The solubility and stability of flurbiprofen in a suitable receiver fluid, and a suitable extraction method and fluid to recover and quantitate flurbiprofen from human pharynx tissue, were investigated using high‐performance liquid chromatography (HPLC). The potential interference of human pharynx tissue in the receiver fluid was also investigated. The HPLC analytical method was successfully validated according to current guidelines. The final receiver fluid demonstrated sufficient solubility and stability, and the extraction method and fluid resulted in >95% recovery of flurbiprofen following exposure to human pharynx tissue. The lower limit of quantitation of flurbiprofen was 0.045 μg/mL in both the receiver and extraction fluids. There was no interference of the human pharynx tissue with the HPLC method. This investigation validated an analytical method for quantitating flurbiprofen, and determined a suitable receiver fluid and extraction method and fluid, which can be used to investigate the permeation and penetration of flurbiprofen through human pharynx tissue using the Franz diffusion cell method.

Objective: Flurbiprofen 8.75 mg spray and lozenge have a rapid onset of action for sore throat relief, suggesting local action, although tissue penetration and the mechanism of local relief have not been determined. This investigation aimed to quantify the permeation and penetration of flurbiprofen, applied as local pharmaceutical forms, into full-thickness cadaveric human mucosal pharynx tissue, representing the clinical scenario as far as possible. Methods: A validated high-performance liquid chromatography method quantified the permeation and penetration of flurbiprofen (spray and lozenge formulations) into human cadaveric pharynx tissue using a micro Franz cell model mimicking physiological and anatomical conditions. Full-thickness mucosal pharynx tissue, consisting of oral epithelium, basement membrane, and lamina propria, was utilized to imitate the in vivo setting. Flurbiprofen was analyzed on the surface of the pharynx tissue, within the pharynx tissue and in receiver fluid, over 60 mins. Results: Flurbiprofen was detected in receiver fluid from 10 mins following spray application and was quantifiable from 20 mins. Flurbiprofen from lozenge was detected from 10 mins and was above the limit of quantitation in receiver fluid from 40 mins. Flurbiprofen recovered from the surface of the pharynx tissue was 24.45% and 8.48% of applied dose for spray and lozenge, respectively. Flurbiprofen recovered within pharynx tissue was 46.50% and 54.65% of applied dose for spray and lozenge, respectively. For flurbiprofen lozenge, recovery within pharynx tissue was 6-fold higher relative to recovery from the pharynx tissue surface. Conclusion: Flurbiprofen from spray and lozenge formulations penetrated human cadaveric pharynx tissue, indicating that flurbiprofen can reach all layers of the pharynx mucosal tissue, including the underlying lamina propria, which contains blood vessels and nerve fibers that contribute to pain during sore throat. This suggests that flurbiprofen may have a local mechanism of action for sore throat, although this has yet to be determined.

Objective: Flurbiprofen 8.75 mg lozenge and spray are used for symptomatic relief of sore throat, with a rapid onset of analgesia suggesting a localized mechanism of action. Building on previous studies, this investigation aimed to use microautoradiography to visualize the depth penetration of radiolabeled flurbiprofen into human pharynx tissue using an ex vivo model. Quantification of flurbiprofen in the tissue was performed to provide a quantitative representation of flurbiprofen distribution through the tissue. Methods: Cadaveric human pharynx tissue was mounted between the donor and receiver compartments of a Franz diffusion cell. After that 8.75 mg spray and dissolved lozenge formulations, containing radiolabeled flurbiprofen, were added to the donor compartment of a Franz diffusion cell. After incubation for one hour, the pharynx tissue was removed, processed, and sectioned both horizontally and vertically. The sections were placed within an imaging cassette to determine the penetration of radiolabeled flurbiprofen visually, before being solubilized to quantify the amount of flurbiprofen present in each section. Results: In the horizontally sectioned samples, flurbiprofen was present in the top layers of all replicates and decreased in intensity throughout the tissue. Of the applied dose, 48.0--99.9% of flurbiprofen was detected in the top one-third of the pharynx tissue, closest to the dosing site, and 0-14.8% of flurbiprofen was detected within the deepest third of pharynx tissue, furthest from the dosing site. In the vertically sectioned tissue samples, radiolabeled flurbiprofen was found at a high intensity at the dosing site and reduced in intensity throughout the thickness of the tissue. Lateral penetration of flurbiprofen was also seen in tissue dosed with the spray. Conclusion:Our findings demonstrate that lozenge and spray formulations of flurbiprofen can penetrate throughout the layers of cadaveric human pharynx tissue in an ex vivo model, as visualized by microautoradiography.