TY  - JOUR
SN  - 1573-904X
UR  - http://dx.doi.org/10.1007/s11095-016-1997-y
JF  - Pharmaceutical Research
A1  - Tuleu, C
A1  - Kendall, R
A1  - Lenoir, J
A1  - Gerrard, S
A1  - Scheuerle, RL
A1  - Slater, NKH
VL  - 34
SP  - 687
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
IS  - 4
ID  - discovery1519657
N2  - 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.  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. Results: Presently an 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.  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 in vitro and existing in vivo assays.
PB  - American Association of Pharmaceutical Scientists
KW  - Nipple Shield Delivery System
KW  -  Slug Mucosal Irritation Assay
KW  -  Skin Tolerability
KW  -  Tablet Excipients
KW  -  Pediatric
TI  - Using 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 system
EP  - 695
AV  - public
Y1  - 2017/02/13/
ER  -