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

Wei, Lijun, Marasini, Nirmal, Li, Gao, Yong, Chul Soon, Kim, Jong Oh and Quan, Qizhe (2012) Development of ligustrazine-loaded lipid emulsion: formulation optimization, characterization and biodistribution. International Journal of Pharmaceutics, 437 1-2: 203-212. doi:10.1016/j.ijpharm.2012.08.027

Author Wei, Lijun
Marasini, Nirmal
Li, Gao
Yong, Chul Soon
Kim, Jong Oh
Quan, Qizhe
Title Development of ligustrazine-loaded lipid emulsion: formulation optimization, characterization and biodistribution
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
Publication date 2012-11-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2012.08.027
Open Access Status Not Open Access
Volume 437
Issue 1-2
Start page 203
End page 212
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Formatted 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 AUC0-180min 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.
Keyword Characterization
Lipid emulsion
Tissue distribution
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2010-0024185
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 04 Jun 2016, 21:57:43 EST by Nirmal Marasini on behalf of Learning and Research Services (UQ Library)