Determination of the Permeation and Penetration of Flurbiprofen into Cadaveric Human Pharynx Tissue.
Franz diffusion cell
chromatography
flurbiprofen
high-pressure liquid
pharynx
Journal
Clinical pharmacology : advances and applications
ISSN: 1179-1438
Titre abrégé: Clin Pharmacol
Pays: New Zealand
ID NLM: 101564865
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
10
2019
accepted:
13
02
2020
entrez:
11
4
2020
pubmed:
11
4
2020
medline:
11
4
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32273779
doi: 10.2147/CPAA.S234227
pii: 234227
pmc: PMC7102892
doi:
Types de publication
Journal Article
Langues
eng
Pagination
13-20Informations de copyright
© 2020 Turner et al.
Déclaration de conflit d'intérêts
Robert Atkinson, Oluwajoba Adegoke, Anuradha Kulasekaran and Tim Shea are employees of Reckitt Benckiser. Rob Turner, Sean Robert Wevrett, Suzanne Edmunds, and Marc Brown are employees of MedPharm Ltd. The authors report no other conflicts of interest in this work.
Références
Otolaryngol Head Neck Surg. 2016 Jul;155(1):166-72
pubmed: 26980919
Eur J Gen Pract. 2016 Jun;22(2):111-8
pubmed: 27028316
Pain Manag. 2018 Mar;8(2):85-94
pubmed: 29381110
J Sleep Res. 2008 Jun;17(2):230-8
pubmed: 18422508
Pharmacology. 2014;94(3-4):143-7
pubmed: 25277061
J Pharm Pharm Sci. 1998 Jan-Apr;1(1):15-30
pubmed: 10942969
J Pharm Sci. 1991 Sep;80(9):820-3
pubmed: 1800701
Biomed Chromatogr. 2019 Aug;33(8):e4499
pubmed: 30667527
J Adv Pharm Technol Res. 2011 Jul;2(3):151-5
pubmed: 22171311
Science. 2001 Nov 30;294(5548):1871-5
pubmed: 11729303
J Chromatogr Sci. 2015 Oct;53(9):1443-8
pubmed: 25820260
Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000
pubmed: 21508345
J Clin Pharm Ther. 2018 Apr;43(2):302-307
pubmed: 29205419
Curr Med Res Opin. 2016 Sep;32(9):1529-38
pubmed: 27146963
J Pain Res. 2017 Jul 06;10:1591-1600
pubmed: 28740426
Int J Clin Pract. 2009 Apr;63(4):606-12
pubmed: 19222617
J Pharm Sci. 1992 Jan;81(1):1-10
pubmed: 1619560
Exp Anim. 2011;60(4):373-84
pubmed: 21791877
Clin Ther. 2015 Mar 1;37(3):515-522
pubmed: 25773460
Cochrane Database Syst Rev. 2013 Nov 05;(11):CD000023
pubmed: 24190439
J Helminthol. 2003 Mar;77(1):27-31
pubmed: 12590661
BMC Ear Nose Throat Disord. 2012 Aug 10;12:9
pubmed: 22883470
Pain. 2014 Feb;155(2):422-428
pubmed: 24231654
J Pain Res. 2019 Dec 27;12:3477-3509
pubmed: 31920372
AAPS PharmSciTech. 2010 Sep;11(3):1432-41
pubmed: 20842539
Drug Metab Pharmacokinet. 2002;17(2):142-9
pubmed: 15618663
J Natl Cancer Inst Monogr. 2001;(29):7-15
pubmed: 11694559
Carcinogenesis. 2006 Jan;27(1):137-45
pubmed: 16000402
Clin Otolaryngol. 2018 Jun;43(3):835-840
pubmed: 29288561
Br J Pain. 2018 Nov;12(4):208-216
pubmed: 30349694
Arch Intern Med. 1984 Mar;144(3):497-500
pubmed: 6703820
Minerva Anestesiol. 2019 Jan;85(1):21-27
pubmed: 29756749
Inflamm Res. 2012 Oct;61(10):1041-52
pubmed: 22890476
Int J Clin Pract. 2011 May;65(5):524-30
pubmed: 21489076
J Invest Dermatol. 1975 Mar;64(3):190-5
pubmed: 123263
Br J Hosp Med (Lond). 2007 Feb;68(2):71-5
pubmed: 17370703
Postgrad Med. 2013 Jul;125(4 Suppl 1):7-18
pubmed: 24547599
Clin Pharmacol Ther. 1988 Aug;44(2):225-31
pubmed: 3293876
Pak J Pharm Sci. 2012 Apr;25(2):365-9
pubmed: 22459463
Curr Drug Deliv. 2017;14(5):725-733
pubmed: 27919213
Br J Clin Pharmacol. 1994 Apr;37(4):392-4
pubmed: 8018462