Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats

Abstract

A novel transdermal delivery of sumatriptan (ST) was attempted by application of dissolving microneedle (DM) technology. Dextran DM (d-DM) and hyaluronate DM (h-DM) were prepared by adding ST solution to dextran solution or hyaluronic acid solution. One DM chip, 1.0 × 1.0 cm, contains 100 microneedle arrays in a 10 × 10 matrix. The mean lengths of DMs were 496.6 ± 2.9 μm for h-DM and 494.5 ± 1.3 μm for d-DM. The diameters of the array basement were 295.9 ± 3.9 μm (d-DM) and 291.7 ± 3.0 μm (h-DM), where ST contents were 31.6 ± 4.5 μg and 24.1 ± 0.9 μg. These results suggest that ST was stable in h-DM. Each DM was administered to rat abdominal skin. The maximum plasma ST concentrations, C_max, and the areas under the plasma ST concentration versus time curves (AUC) were 44.6 ± 4.9 ng/ml and 24.6 ± 3.9 ng · h/ml for h-DM and 38.4 ± 2.7 ng/ml and 14.1 ± 1.5 ng · h/ml for d-DM. The bioavailabilities of ST from DMs were calculated as 100.7 ± 18.8% for h-DM and 93.6 ± 10.2% for d-DM. Good dose dependency was observed on C_max and AUC. The stability study of ST in DM was performed for 3 months under four different conditions, −80, 4, 23, and 50°C. At the end of incubation period, they were, respectively, 100.0 ± 0.3%, 97.8 ± 0.2%, 98.8 ± 0.2%, and 100.7 ± 0.1%. These suggest the usefulness of DM as a noninvaisive transdermal delivery system of ST to migraine therapy.

Keywords::

• Dissolving microneedles
• array chip
• sumatriptan
• bioavailability
• transdermal delivery
• rats