Development of ligustrazine-loaded lipid emulsion: Formulation optimization, characterization and biodistribution

Title
Development of ligustrazine-loaded lipid emulsion: Formulation optimization, characterization and biodistribution
Author(s)
김종오Lijun Wei[Lijun Wei]마라시니니르말Gao Li[Gao Li]용철순Qizhe Quan[Qizhe Quan]
Keywords
DRUG-DELIVERY; INTRAVENOUS EMULSION; LIVER-INJURY; BURN TRAUMA; IN-VITRO; TETRAMETHYLPYRAZINE; OIL; PHARMACOKINETICS; MICROEMULSIONS; HYDROCHLORIDE
Issue Date
201211
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.437, no.1-2, pp.203 - 212
Abstract
Ligustrazine is a traditional Chinese medicine used to treat various cardiovascular and neurovascular complications. However, this compound exhibits rapid first-pass metabolism, a short biological half-life, low stability and potential vascular irritation that restrict its use for long-term therapy. The use of a lipid emulsion as a carrier for intravenous administration of ligustrazine might provide sustained and prolonged release, thereby reducing the frequency of administration and improving patient compliance. The main purpose of our study was to develop a highly stable and sterile optimal formulation of a ligustrazine lipid emulsion (LLE) and to evaluate its pharmacokinetic behavior and tissue distribution in rats. The final optimal formulation consisted of soybean oil (12.0%), oleic acid (0.6%), lecithin (1.0%), poloxamer 188 (0.6%) and glycerol (2.25%). The average particle size, polydispersity index (PDI), zeta-potential and pH of the final product were 215.0 +/- 2.5 nm, 0.076 +/- 0.033, -40.4 +/- 5.3 mV and 7.25 +/- 0.05, respectively. The LLE was stable for at least three months at room temperature. In vitro drug release studies of the LLE suggested a sustained release profile, which was further confirmed by in vivo pharmacokinetic studies in rats. The area under the drug concentration-time curve from 0 h to 10 h (AUC0-10h) for LLE was increased by 1.6-fold compared with that of the commercially available ligustrazine injection (LI), suggesting enhanced bioavailability from the lipid-based emulsion. Furthermore, a tissue distribution study showed significant improvement in the distribution pattern of ligustrazine with a higher AUC(0-180min) observed in all tissues for LLE than for LI. In conclusion, LLE, with excellent stability, improved pharmacokinetics and tissue distribution, demonstrates great potential for the delivery of ligustrazine for clinical applications. (C) 2012 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/26960http://dx.doi.org/10.1016/j.ijpharm.2012.08.027
ISSN
0378-5173
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약학대학 > 약학부 > Articles
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