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dc.contributor.authorKendall, Ren
dc.contributor.authorLenoir, Jen
dc.contributor.authorGerrard, Sen
dc.contributor.authorScheuerle, Rebekahen
dc.contributor.authorSlater, Nigelen
dc.contributor.authorTuleu, Cen
dc.date.accessioned2017-02-27T16:09:06Z
dc.date.available2017-02-27T16:09:06Z
dc.date.issued2017-04-01en
dc.identifier.issn0724-8741
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262796
dc.description.abstract$\textbf{PURPOSE}$: Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form $\textbf{METHODS}$: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]. Slugs were exposed to blends slurried in human breast milk to assess their stinging, itching or burning potential, using objective values such as mucus production to categorize irritation potency $\textbf{RESULTS}$: Presently an $\textit{in vivo}$ assay, previously validated for prediction of ocular and nasal irritation, was used as an alternative to vertebrate models to anticipate the potential maternal dermatological tolerability issues to NSDS tablet components. The excipients did not elicit irritancy. However, mild irritancy was observed when zinc sulphate was present in blends. $\textbf{CONCLUSION}$: These promising good tolerability results support the continued investigation of these excipients within NSDS rapidly disintegrating tablet formulations. Topical local tolerance effects being almost entirely limited to irritation, the slug assay potentially adds to the existing preformulation toolbox, and may sit in between the $\textit{in vitro}$ and existing $\textit{in vivo}$ assays.
dc.description.sponsorshipThis work was made possible through the support of the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the UK Department for International Development (DFID). Additional support was provided by the Gates Cambridge Trust.
dc.languageEnglishen
dc.language.isoenen
dc.publisherSpringer
dc.titleUsing the Slug Mucosal Irritation Assay to Investigate the Tolerability of Tablet Excipients on Human Skin in the Context of the Use of a Nipple Shield Delivery Systemen
dc.typeArticle
prism.endingPage695
prism.publicationDate2017en
prism.publicationNamePharmaceutical Researchen
prism.startingPage687
prism.volume34en
dc.identifier.doi10.17863/CAM.8085
dcterms.dateAccepted2016-07-08en
rioxxterms.versionofrecord10.1007/s11095-016-1997-yen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-04-01en
dc.contributor.orcidSlater, Nigel [0000-0002-0207-9440]
dc.identifier.eissn1573-904X
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2018-02-13


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