Naltrexone salt selection for enhanced transdermal permeation through microneedle-treated skin

作者：Milewski Mikolaj; Pinninti Raghotham R; Stinchcomb Audra L^*

来源：Journal of Pharmaceutical Sciences, 2012, 101(8): 2777-2786.

DOI：10.1002/jps.23189

• transdermal drug delivery
• microneedles
• naltrexone
• salts
• skin
• in vitro models
• diffusion
• permeability
• solubility

The passive delivery rate of naltrexone (NTX) through intact skin is too slow to achieve therapeutic plasma levels in humans from a reasonably sized transdermal patch. A physical enhancement methodmicroneedles (MNs)has been shown to afford a substantial increase in the percutaneous flux of NTX hydrochloride in vitro. However, for better therapeutic effect and decrease in the transdermal patch area, further enhancement is desired. The purpose of this study was to identify a NTX salt that would (1) provide elevated in vitro percutaneous drug transport across MN-treated skin as compared with that of the NTX hydrochloride and (2) prove nonirritating to the skin in vivo. The pH-solubility profiles of NTX salts were investigated with three drug salts showing improved solubility at physiologically relevant skin surface pH of 5.0. The skin-irritation potential of NTX glycolate and lactate gels was not greater than that of placebo gel in the guinea pig model. Additionally, in vitro diffusion studies indicated that NTX glycolate provides around 50% enhancement in the flux through MN-treated skin at the cost of doubling the drug concentration in the donor solution. Overall, a new NTX glycolate salt appears to be a promising candidate for MN-assisted transdermal drug delivery system.

• 出版日期2012-8