AZONE ANALOGS AS PENETRATION ENHANCERS - EFFECT OF DIFFERENT VEHICLES ON HYDROCORTISONE ACETATE SKIN PERMEATION AND RETENTION

The permeation and skin retention of hydrocortisone-21-acetate in hairless mouse skin in vitro was examined following topical pretreatment with four novel enhancers in four vehicles: isopropyl myristate (IPM), N-methyl-2-pyrrolidinone, (MP), polyethylene glyco 1400 (PEG), and caprylic/capric/linoleic triglyceride (CT, Miglyol 818(R)). Controls included no vehicle pretreatment and vehicle pretreatment one hour prior to drug application to the skin. The standard enhancer studied was Atone. With enhancer 1 [N-(1-oxododecyl)morpholine], the rank order for 24 hour cumulative receptor steroid concentrations Q(24) (mu M) was PEG > IPM > MP/CT; for enhancer 2 [N-dodecyl-2-piperidinone]: PEG > IPM/MP/CT; for enhancer 3[N-dodecyl-2-pyrrolidinone]: MP > CT/PEG/IPM; for enhancer 4 [N-(1-oxotetradecyl)hexahydro-2-oxo-1H-azepine]: PEG/MP/IPM > CT. For Q(24) controls, one hour pretreatment with vehicles alone, rank order was IPM > MP/CT > PEG. Coadministration of the steroid with enhancer 2 with PEG or with propylene glycol reduced enhancer effectiveness compared to pretreatment with vehicle alone.