Document Detail


Evaluation of self-dissolving needles containing low molecular weight heparin (LMWH) in rats.
MedLine Citation:
PMID:  17826015     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yukako Ito; Aiko Murakami; Tomohiro Maeda; Nobuyuki Sugioka; Kanji Takada
Related Documents :
21044025 - The plasma coagulation cascade: potential targets for novel anticoagulants in major low...
10929935 - Dalteparin: an update of its pharmacological properties and clinical efficacy in the pr...
23223655 - Hypertriglyceridaemia-induced pancreatitis: a contributory role of capecitabine?
24310425 - Factors and mechanisms for pharmacokinetic differences between pediatric population and...
3887555 - Gastroscopic findings after treatment with enteric-coated and plain naproxen tablets in...
10780805 - Sensitization to apomorphine in pigeons is due to conditioning, subject to generalizati...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-06
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  349     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2007-12-31     Completed Date:  2008-03-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  124-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. yukako@mb.kyoto-phu.ac.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Absorption
Animals
Anticoagulants / administration & dosage*,  pharmacokinetics
Chondroitin / chemistry
Dextrans / chemistry
Dose-Response Relationship, Drug
Drug Stability
Drug Storage
Excipients
Factor Xa / metabolism
Heparin, Low-Molecular-Weight / administration & dosage*,  pharmacokinetics
Male
Needles
Rats
Rats, Wistar
Solubility
Temperature
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Excipients; 0/Heparin, Low-Molecular-Weight; 9004-54-0/Dextrans; 9007-27-6/Chondroitin; EC 3.4.21.6/Factor Xa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effect of butylated hydroxytoluene on bull spermatozoa frozen in egg yolk-citrate extender.
Next Document:  Effect of Acanthopanax senticosus on 5-hydroxytryptamine synthesis and tryptophan hydroxylase expres...