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In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L-lactide- co-glycolide) nanoparticles in rats.
Chirality. 2004 Feb; 16(2):119-25.C

Abstract

Flurbiprofen (FL) is a chiral 2-arylpropionate used clinically as the racemate (rac-FL). This study was undertaken to investigate the influence of sustained release formulation on the pharmacokinetics of flurbiprofen enantiomers (-) -R-FL and (+)-S-FL. Therefore, a stereoselective high-performance liquid chromatographic (HPLC) method was developed and validated for the rapid, quantitative determination of (-)-R-FL and (+)-S-FL in rat plasma. Flurbiprofen-loaded poly(D,L-lactide-co-glycolide) nanoparticles (rac-FL-PLGA) were prepared by in emulsion-solvent evaporation technique. Optimum conditions for rac-FL-PLGA nanoparticle preparation were considered, and the in vitro release of rac-FL, R-FL, and S-FL were followed up to 48 h in phosphate buffer (pH 7.4). The three tested formulations revealed approximately zero-order release of either (-)-R-FL or S-FL up to 24 h with r >/= 0.97.Surprisingly, there was no significant difference between t(50%) of the three formulations (21.6 +/- 1.1 h). The stereoselective disposition of the sustained release rac-FL deliverv system was investigated in rats. There was a rapid release of R-FL, S-FL, or rac-FL followed by a slower one and C(max) values were observed after 2.5 +/- 2.5, 8.3 +/- 3.4 and 8.86 +/- 3.6 h of (-)-R-FL, (+)-S-FL, and rac-FL, respectively, after nanoparticle administration. PLGA nanoparticles increased the mean retention time (MRT) of S-FL by 2.7-fold, from 6.8 to 16.3 h, compared to rac-FL. Although the dose of rac-FL-PLGA nanoparticles was only 2.5 times higher than that of the drug in the suspension, the mean (+)-S-FL concentration after 12 h was 3.4 times higher in the case of nanoparticles than after the free form, 10.35 +/- 1.6 and 3.04 +/- 1.1 mg/l, respectively. The area under the concentration-time curve (AUC) values of (+)-S-FL and rac-FL were about 2.5-fold higher after the nanoparticles compared to suspension, while the AUC of the (-)-R-FL was about 3.5 times higher. This difference may indicate that the two enantiomers have different absorption kinetics. The present study provides evidence that the sorption of racemic flurbiprofen to PLGA nanoparticles was successful in maintaining (at least up to 12 h) elevated plasma drug concentrations of (+)-S-FL in rats. Chirality 16:119-125, 2004.

Authors+Show Affiliations

Radwan MA
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. mradwan@ksu.edu.sa
Aboul-Enein HY
No affiliation info available

MeSH

AnimalsChromatography, High Pressure LiquidDrug CarriersFlurbiprofenLactic AcidMaleNanotechnologyParticle SizePolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRatsRats, WistarStereoisomerism

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14712475

Citation

Radwan, Mahasen A., and Hassan Y. Aboul-Enein. "In Vitro Release and Stereoselective Disposition of Flurbiprofen Loaded to poly(D,L-lactide- Co-glycolide) Nanoparticles in Rats." Chirality, vol. 16, no. 2, 2004, pp. 119-25.
Radwan MA, Aboul-Enein HY. In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L-lactide- co-glycolide) nanoparticles in rats. Chirality. 2004;16(2):119-25.
Radwan, M. A., & Aboul-Enein, H. Y. (2004). In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L-lactide- co-glycolide) nanoparticles in rats. Chirality, 16(2), 119-25.
Radwan MA, Aboul-Enein HY. In Vitro Release and Stereoselective Disposition of Flurbiprofen Loaded to poly(D,L-lactide- Co-glycolide) Nanoparticles in Rats. Chirality. 2004;16(2):119-25. PubMed PMID: 14712475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L-lactide- co-glycolide) nanoparticles in rats. AU - Radwan,Mahasen A, AU - Aboul-Enein,Hassan Y, PY - 2004/1/9/pubmed PY - 2004/9/1/medline PY - 2004/1/9/entrez SP - 119 EP - 25 JF - Chirality JO - Chirality VL - 16 IS - 2 N2 - Flurbiprofen (FL) is a chiral 2-arylpropionate used clinically as the racemate (rac-FL). This study was undertaken to investigate the influence of sustained release formulation on the pharmacokinetics of flurbiprofen enantiomers (-) -R-FL and (+)-S-FL. Therefore, a stereoselective high-performance liquid chromatographic (HPLC) method was developed and validated for the rapid, quantitative determination of (-)-R-FL and (+)-S-FL in rat plasma. Flurbiprofen-loaded poly(D,L-lactide-co-glycolide) nanoparticles (rac-FL-PLGA) were prepared by in emulsion-solvent evaporation technique. Optimum conditions for rac-FL-PLGA nanoparticle preparation were considered, and the in vitro release of rac-FL, R-FL, and S-FL were followed up to 48 h in phosphate buffer (pH 7.4). The three tested formulations revealed approximately zero-order release of either (-)-R-FL or S-FL up to 24 h with r >/= 0.97.Surprisingly, there was no significant difference between t(50%) of the three formulations (21.6 +/- 1.1 h). The stereoselective disposition of the sustained release rac-FL deliverv system was investigated in rats. There was a rapid release of R-FL, S-FL, or rac-FL followed by a slower one and C(max) values were observed after 2.5 +/- 2.5, 8.3 +/- 3.4 and 8.86 +/- 3.6 h of (-)-R-FL, (+)-S-FL, and rac-FL, respectively, after nanoparticle administration. PLGA nanoparticles increased the mean retention time (MRT) of S-FL by 2.7-fold, from 6.8 to 16.3 h, compared to rac-FL. Although the dose of rac-FL-PLGA nanoparticles was only 2.5 times higher than that of the drug in the suspension, the mean (+)-S-FL concentration after 12 h was 3.4 times higher in the case of nanoparticles than after the free form, 10.35 +/- 1.6 and 3.04 +/- 1.1 mg/l, respectively. The area under the concentration-time curve (AUC) values of (+)-S-FL and rac-FL were about 2.5-fold higher after the nanoparticles compared to suspension, while the AUC of the (-)-R-FL was about 3.5 times higher. This difference may indicate that the two enantiomers have different absorption kinetics. The present study provides evidence that the sorption of racemic flurbiprofen to PLGA nanoparticles was successful in maintaining (at least up to 12 h) elevated plasma drug concentrations of (+)-S-FL in rats. Chirality 16:119-125, 2004. SN - 0899-0042 UR - https://www.unboundmedicine.com/medline/citation/14712475/In_vitro_release_and_stereoselective_disposition_of_flurbiprofen_loaded_to_poly_DL_lactide__co_glycolide__nanoparticles_in_rats_ DB - PRIME DP - Unbound Medicine ER -