Purpose. To investigate the influence of agitation conditions on the in vitro release rate of leuprolide from leuprolide loaded microspheres. Methods. Leuprolide loaded PLGA (Resomer® RG502H and RG503H) microspheres were prepared by a solvent extraction/evaporation method. In vitro leuprolide release was performed in 10 ml of 0.1 M phosphate buffer solution pH 7.4 at 37°C under continuous or once a week agitation (agitation for 1 minute). At predetermined intervals, the supernatant was withdrawn and analyzed for leuprolide concentration by RP-HPLC. Elution was performed in a gradient manner with mobile phase A: water with 0.1% trifluoroacetic acid (TFA) and B: water:acetonitrile (50:50, v:v) with 0.1% TFA. At predetermined time points, leuprolide was extracted from the remaining microspheres and assayed by RP-HPLC to assess mass balance. Polymer hydration and mass loss (ML) were followed. Results. Leuprolide release was higher when in vitro release was carried out under continuous agitation with respect to that performed under once a week agitation for both polymers. Polymer ML was also higher under continuous agitation than that under once a week agitation. Leuprolide mass balance was considered satisfactory for the two microspheres preparations. In the case of RG502H, microspheres incubated under continuous agitation showed a higher DH between day 1 and day 12 than those under once a week agitation. For the other preparation, the hydration rate was nearly the same under both agitation conditions. Conclusion. The agitation conditions have a large influence on the drug release rate. It is a fundamental parameter for the in vitro in vivo correlation (IVIVC) and should be considered for further development and improvements of dosage form design and for release protocols.

Effect of agitation conditions on the in vitro release of leuprolide loaded microspheres.

SCHOUBBEN, Aurelie Marie Madeleine;
2006

Abstract

Purpose. To investigate the influence of agitation conditions on the in vitro release rate of leuprolide from leuprolide loaded microspheres. Methods. Leuprolide loaded PLGA (Resomer® RG502H and RG503H) microspheres were prepared by a solvent extraction/evaporation method. In vitro leuprolide release was performed in 10 ml of 0.1 M phosphate buffer solution pH 7.4 at 37°C under continuous or once a week agitation (agitation for 1 minute). At predetermined intervals, the supernatant was withdrawn and analyzed for leuprolide concentration by RP-HPLC. Elution was performed in a gradient manner with mobile phase A: water with 0.1% trifluoroacetic acid (TFA) and B: water:acetonitrile (50:50, v:v) with 0.1% TFA. At predetermined time points, leuprolide was extracted from the remaining microspheres and assayed by RP-HPLC to assess mass balance. Polymer hydration and mass loss (ML) were followed. Results. Leuprolide release was higher when in vitro release was carried out under continuous agitation with respect to that performed under once a week agitation for both polymers. Polymer ML was also higher under continuous agitation than that under once a week agitation. Leuprolide mass balance was considered satisfactory for the two microspheres preparations. In the case of RG502H, microspheres incubated under continuous agitation showed a higher DH between day 1 and day 12 than those under once a week agitation. For the other preparation, the hydration rate was nearly the same under both agitation conditions. Conclusion. The agitation conditions have a large influence on the drug release rate. It is a fundamental parameter for the in vitro in vivo correlation (IVIVC) and should be considered for further development and improvements of dosage form design and for release protocols.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/42206
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