TOPICAL APPLICATION OF AZONE ANALOGS TO HAIRLESS MOUSE SKIN - A HISTOPATHOLOGICAL STUDY

Eight dermal penetration enhancers were-evaluated for irritancy potent ial on hairless mice. The enhancers included propylene glycol and isop ropyl myristate as controls. Novel enhancers included: Atone or 1-dode cylhexahydro-2H- azepin-2-one (1); N-dodecyl-2-pyrrolidinone (2); N-do decyl-2-piperidinone (3); N-dodecyl-N-(2-methoxyethyl)acetamide (4); N -(2,2-dihydroxyethyI)dodecylamine (5); and 2-(1-nonyl)1,3-dioxolane (6 ). The analogs were tested at concentrations of 10% (approx. 0.4 M) in the vehicle propylene glycol and at 100%. Plastic cups containing the solutions were attached to the dorsal side of the animals (n = 3) for 24 h. A biopsy technique was used and the treated skin and adjacent u ntreated skin were fixed in 10% buffered formalin, embedded in paraffi n, and stained with haematoxylin and eosin. Histological examination c oupled with visual observation allowed for assessment of damage to the epidermal and dermal layers of the skin. Propylene glycol and isoprop yl myristate were found to have no discernible effects on the skin eve n at 100%. Enhancers 1 and 6 were found to have virtually no effect on the skin at 10% in propylene glycol. Enhancers 2, 3, and 5 at 10% wer e found to have some effects on the skin and are considered to be mild -to-moderate irritants. Enhancer 4 at 10% and enhancers 1, 2, 3, and 6 at 100% were found to cause severe irritation to the skin.