title: Evaluation of self-dissolving needles containing low molecular weight heparin (LMWH) in rats.
abstract: Feasibility study of self-dissolving needles containing polysaccharide was performed. Low molecular weight heparin (LMWH) was used as a representative polysaccharide. Using chondroitin, dextran and dextrin as the base, self-dissolving needles (SDN) were prepared. The obtained SDNs were evaluated in rat absorption experiment, where pharmacological availability (PA) was calculated by comparing the plasma anti-Xa activity vs. time curves between SDNs and i.v. solution. After the insertion of SDNs to rats skin where the doses of LMWH were 25, 50 and 100 IU/kg, plasma samples were collected for 6h and anti-Xa activity was measured as the pharmacological index of LMWH. The anti-Xa level was maintained above 0.2 IU/ml, the therapeutic level, for about 2h at a dose of 100 IU/kg. Almost the same PAs of LMWH were obtained with dextran and dextrin SDNs, 97.7% and 102.3%, though lower PA was obtained with chondroitin SDN, 81.5%. In vitro dissolution experiment showed that LMWH was released from dextran, dextrin and chondroitin SDNs within 10 min. The T(50%)s were 0.84+/-0.06 min for dextran SDN, 1.07+/-0.12 min for chondroitin SDN and 2.11+/-0.31 min for dextrin SDN, respectively. Plasma anti-Xa activity vs. time profiles showed good dose-dependency in the 25-100 IU/kg range and high PAs were obtained, 90.0% for 25 IU/kg, 95.4% for 50 IU/kg and 97.7% for 100 IU/kg from dextran SDNs. Stability experiment was performed with dextran SDNs for 3 months. Above 97% of LMWH were remained in SDNs under three different conditions, -80, 4 and 40 degrees C. These results suggest the usefulness of SDN to polysaccharide drug.
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. yukako@mb.kyoto-phu.ac.jp
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ito
authors.forename: Aiko
authors.initials: A
authors.lastname: Murakami
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugioka
authors.forename: Kanji
authors.initials: K
authors.lastname: Takada
mesh_terms: D000042:Absorption; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002807:Chondroitin / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients; D015951:Factor Xa / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009339:Needles; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013696:Temperature