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Biodisposition of PEG-coated lipid microspheres of indomethacin in arthritic rats.

Authors :
Palakurthi S
Vyas SP
Diwan PV
Source :
International journal of pharmaceutics [Int J Pharm] 2005 Feb 16; Vol. 290 (1-2), pp. 55-62. Date of Electronic Publication: 2005 Jan 07.
Publication Year :
2005

Abstract

Conventional lipid microspheres (LM) were prepared using soybean oil and lipid at a 5.5:1 weight ratio with lipid phase consisting of PC (phosphatidyl choline):CH (cholesterol) (1:0.5) by molar ratio. The average diameter of the particles was 150 nm. Long-circulating microspheres (S-LM) were also prepared similarly but the lipid phase consisted of PC:CH:DSPE-PEG (phosphatidyl choline:cholesterol:distearoyl phosphatidyl ethanolamine-polyethylene glycol) 1:0.5:0.16 by molar ratio. A comparative biodistribution study was conducted between free indomethacin and lipo-indomethacin (LM and S-LM) in the arthritic rats by administering the formulations at a dose equivalent to 12 mg of indomethacin/kg. It was observed that the free drug as well as the encapsulated drug followed biphasic clearance from the blood. Pharmacokinetic parameters, such as AUC(0-t), terminal half-life, MRT increased significantly when the drug was used in encapsulated form (p < 0.05). Clearance of the drug was reduced 1.4 times with the conventional lipid microspheres and was reduced three-fold when encapsulated in polyethylene glycol-coated lipid microspheres. The overall drug targeting efficiency (T(e)) with the PEG-coated lipid microspheres was 7.5-fold higher than the conventional lipid microspheres. The high accumulation of the drug in arthritic paw with S-LM system may be accounted for by the reduced uptake by RES cells, and thereby, availability for extravascularization in the inflammatory tissues.

Details

Language :
English
ISSN :
0378-5173
Volume :
290
Issue :
1-2
Database :
MEDLINE
Journal :
International journal of pharmaceutics
Publication Type :
Academic Journal
Accession number :
15664130
Full Text :
https://doi.org/10.1016/j.ijpharm.2004.11.017