Influence of penetration enhancer on drug permeation from volatile formulations

• Published in: International journal of pharmaceutics Vol. 439; no. 1-2; pp. 260 - 268
• Main Authors: Santos, P., Watkinson, A.C., Hadgraft, J., Lane, M.E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2012
• Subjects: Administration, Cutaneous; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - chemistry; balance studies; diffusivity; ethanol; Female; Fentanyl; Fentanyl - administration & dosage; Fentanyl - chemistry; Humans; In Vitro Techniques; Isopropyl myristate; mechanism of action; Myristates - administration & dosage; Myristates - chemistry; nonlinear models; Octyl salicylate; Permeability; Propylene glycol; Propylene Glycol - administration & dosage; Propylene Glycol - chemistry; Salicylates - administration & dosage; Salicylates - chemistry; Saturation; Skin - metabolism; Skin Absorption - drug effects; solubility; Supersaturation; Volatilization; Isopropyl myristate; Fentanyl; Propylene glycol; Supersaturation; Octyl salicylate; Saturation
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.09.031

Previously we have reported the influence of supersaturation on the permeation of fentanyl across model membranes and skin. The findings indicated that the vehicle and, specifically its residence time in skin, influence the ability of the formulation to enhance membrane drug permeation. The aim of the present study was to probe the role of vehicle components on (trans)dermal drug delivery in more detail. To this end, three commonly used chemical penetration enhancers were selected for investigation namely, propylene glycol (PG), octyl salicylate (OSAL) and isopropyl myristate (IPM). A further objective was to clarify the mechanism of action of OSAL. Model spray formulations were prepared consisting of 10% (v/v) of individual enhancers in ethanol. Saturated and supersaturated systems were evaluated for their ability to promote fentanyl transport across human skin in vitro. Mass balance studies and determination of the extent of uptake of enhancers by skin were also conducted. The results indicated that increasing the degree of drug saturation (DS) does not promote drug permeation for formulations in PG but increasing drug DS did promote drug permeation for IPM and some OSAL systems. This probably reflects faster depletion of PG compared with IPM and OSAL. Non-linear modelling of the permeation data indicated that PG and IPM act to promote drug solubility in the membrane whereas OSAL appears to act as a skin penetration enhancer by increasing drug diffusivity in the skin.