Drug Delivery Technology

T R ANSDERMAL

DELIVERY

been investigated. To date however, oxycodone has not been administered via the topical (dermal) route.

The pharmacokinetics of topically applied TPM/Oxycodone gel (approx 5 mg oxycodone/kg body weight) versus positive control (oxycodone, water) was determined in rats (n = 6/treatment group). Rats were dosed twice daily with their treatment (AM and PM, approx 10:00 hours and 15:00 hours) for 3 days and a single dose on day 4 (AM dose only). From this, it was observed that TPM/Oxycodone significantly increased plasma oxycodone concentrations compared to the positive control, indicating TPM enhanced transdermal permeation of oxycodone in rats (Figure 4A).

As observed with morphine, the increased concentrations of oxycodone delivered transdermally resulted in analgesia, as measured by longer paw withdrawal latencies (Figure 4B). TPM/Oxycodone-mediated analgesia ( 10 mg oxycodone/kg) was approximately 12 seconds longer than TPM and oxycodone positive control ( 10 mg oxycodone/kg), indicating that TPM increases skin permeation of topically applied oxycodone. TPM/Oxycodone-mediated analgesia was equivalent to 3 mg/kg IP oxycodone, but was longer lasting. Combined, these data demonstrate that TPM formulations increase the permeation of oxycodone through the skin in concentrations sufficient to have a therapeutic effect. Furthermore, a single dose of TPM/Oxycodone results in prolonged duration of action, lasting at least 6 hours in rats.

However, due to the relatively large size and charged nature of most peptides and proteins (insulin 6 kDa), the efficacy in passive transdermal delivery is extremely poor. Systems involving electric current, such as iontophoresis and electroporation,

FIGURES

can drive such molecules across the stratum corneum and are beginning to show promise for insulin delivery. ^12-16We sought to investigate whether the penetration-enhancing effects of TPM would facilitate the passive transdermal delivery of a large

4A & 4B

INSULIN

Currently, the only means of insulin treatment is via daily injection, which can be a significant burden for people with diabetes. Insulin therefore represents a very attractive target for transdermal delivery.