title: Two-layered dissolving microneedles formulated with intermediate-acting insulin.
abstract: Two-layered dissolving microneedles (DMs) containing intermediate-acting insulin, protamine sulfate insulin (PSI), were prepared. Then a pharmacodynamic study was performed to evaluate the prolonged hypoglycemic effects in rats. The DMs were approximately 497±5 μm long, with 303±3 μm diameter at their base. The length of the insulin loaded space was 182±4 μm. PSI contents in DMs were 0.51±0.02 IU. A three-month stability study showed that 99.9±1.4% of PSI was recovered at 4 °C. As the temperature increased to 40 °C, recovery decreased to 97.5±2.0%. PSI was released within 5 min from DMs. Hypoglycemic effects of PSI DMs were evaluated in rats where subcutaneous injection preparations were used as references. Total area above the plasma glucose level (% of the pre-dose level) vs. time curve as an index of hypoglycemic effect was 144.0±16.0% h and 243.3±8.5% h for PSI DMs at 1.46 and 3.28 IU/kg. The relative pharmacologic availability of PSI from DMs were 100.2±9.8% and 91.4±4.1%. No significant difference of hypoglycemic curves was found between DMs and injection solutions, which suggests the usefulness of two-layered DMs of PSI for the displacement therapy of sc injection preparation.
authors: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan. yukako@mb.kyoto-phu.ac.jp
authors: Yukako
authors: Y
authors: Ito
authors: Muneyuki
authors: M
authors: Hirono
authors: Keizo
authors: K
authors: Fukushima
authors: Nobuyuki
authors: N
authors: Sugioka
authors: Kanji
authors: K
authors: Takada
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008845:Microinjections; D009339:Needles; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin