Analgesic Efficacy and Transdermal Penetration of Topical Gabapentin Creams: Finding an Optimal Dose and Pre-treatment Time.

Many patients with chronic neuropathic pain continue to suffer despite traditional pharmacotherapy. As a result, pharmacists commonly compound gabapentin into creams, gels, and ointments as an alternative treatment option. In this study, various concentrations (1%, 5%, and 10%) of topical gabapentin compounded in Lipoderm were applied at various pre-treatment times (30 minutes, 1 hour, and 4 hours) to investigate what gabapentin concentration and pre-treatment time best attenuates formalin-induced nociceptive behaviors in a rodent model. A 30-minute pre-treatment with 5% gabapentin demonstrated maximum attenuation of nociceptive behaviors in this in vivo preclinical pain model. Nociceptive behaviors unexpectedly increased when gabapentin concentration or pre-treatment time was increased, suggesting both antinociceptive and pronociceptive effects of transdermal gabapentin administration. Gabapentin permeation into the skin and deeper tissues of the hindpaw was measured following the in vivo study. Skin and deep tissue permeation of gabapentin was both dose and time-dependent. Maximum deep-tissue permeation occurred within 30 minutes of topical application. Skin concentrations increased with a longer 1-hour pre-treatment. Minimal skin and deeper tissue levels were found following a 4-hour pre-treatment. These results suggest that topical gabapentin may be antinociceptive in a rodent formalin model at specific doses and pre-treatment intervals.

In vitro skin penetration and skin content of progesterone from various topical formulations.

Progesterone has been compounded by pharmacists over the last decade using a variety of different dosage forms including, suppositories, troches, solutions, capsules, nasal sprays, creams, ointments, and gels. In particular, the topical/transdermal route has become very popular among physicians, compounders, and patients. There are a few studies in the medical literature that address the transdermal permeation of progesterone from topically applied dosageforms. The results are typically controversial with some studies showing permeation and others showing little to no permeation. Coupled with the high saliva levels that are often seen in patients undergoing topical/transdermal treatment with progesterone and the accompanying lack of progesterone blood levels, the transdermal route of delivery for progesterone is controversial. In this study, we examined the transdermal penetration of progesterone from four different formulations and the skin retention of progesterone in porcine skin. Our results indicate that only minute quantities of progesterone transdermally penetrated through the porcine skin. However, there was significant partitioning of progesterone in the skin tissues. Consequently, these results suggest that the lymphatic circulation that exists in the skin may potentially account for the systemic delivery of topically applied progesterone that is often observed clinically.