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Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique.

Tabbakhian M, Hasanzadeh F, Tavakoli N, Jamshidian Z - Res Pharm Sci (2014 Sep-Oct)

Bottom Line: A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE.The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances.As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Novel Drug Delivery Systems Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.

No MeSH data available.


Related in: MedlinePlus

The contour plots of release%45 min, DE2% and MDT of glibenclamide release in pH 9.5 from glibenclamidesolid dispersion formulations comprising HPMCE5 (A), PEG6000 (B), and Poloxamer407 (C) of various ratios, prepared by the SE method.
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Figure 7: The contour plots of release%45 min, DE2% and MDT of glibenclamide release in pH 9.5 from glibenclamidesolid dispersion formulations comprising HPMCE5 (A), PEG6000 (B), and Poloxamer407 (C) of various ratios, prepared by the SE method.

Mentions: In this kind of plot the changes in the response due to the change of the proportion of a single component, while all other components are kept at a fixed value, is shown. Once a reference mixture has been selected (often the centroid of the experimental region), the graph exhibits the variation of the response moving, along the component axes, away from the reference mixture. The response trace plot (Fig. 6) illustrates that HPMC had a considerable effect on release%45 min. Higher values of response can be seen where higher levels of PEG6000, with respect to the centroid, is used. Finally, the response variation looks sigmoidal with poloxamer407 changing along the centroid, although the magnitudes of these variations are relatively small. Figs 7 and 8 are typical two-dimensional contour diagrams indicating percent release in 45 min, DE and MDT of GLIB as functions of formulations variables. In Fig. 7, the top point of the polygonal, restricted in the triangle, represents the highest HPMCE5 fraction used, whereas the base represents lowest HPMC fraction (i.e. 50%), with PEG6000 and poloxamer407 at their higher fractions, respectively at left and right points of the base. As seen, e.g. in the contour plot of release%45 min, the higher values of the response were observed where the fractions of HPMCE5, PEG6000, and poloxamer407 were at higher, lower, and close to middle values used in the SE formulations.


Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique.

Tabbakhian M, Hasanzadeh F, Tavakoli N, Jamshidian Z - Res Pharm Sci (2014 Sep-Oct)

The contour plots of release%45 min, DE2% and MDT of glibenclamide release in pH 9.5 from glibenclamidesolid dispersion formulations comprising HPMCE5 (A), PEG6000 (B), and Poloxamer407 (C) of various ratios, prepared by the SE method.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318002&req=5

Figure 7: The contour plots of release%45 min, DE2% and MDT of glibenclamide release in pH 9.5 from glibenclamidesolid dispersion formulations comprising HPMCE5 (A), PEG6000 (B), and Poloxamer407 (C) of various ratios, prepared by the SE method.
Mentions: In this kind of plot the changes in the response due to the change of the proportion of a single component, while all other components are kept at a fixed value, is shown. Once a reference mixture has been selected (often the centroid of the experimental region), the graph exhibits the variation of the response moving, along the component axes, away from the reference mixture. The response trace plot (Fig. 6) illustrates that HPMC had a considerable effect on release%45 min. Higher values of response can be seen where higher levels of PEG6000, with respect to the centroid, is used. Finally, the response variation looks sigmoidal with poloxamer407 changing along the centroid, although the magnitudes of these variations are relatively small. Figs 7 and 8 are typical two-dimensional contour diagrams indicating percent release in 45 min, DE and MDT of GLIB as functions of formulations variables. In Fig. 7, the top point of the polygonal, restricted in the triangle, represents the highest HPMCE5 fraction used, whereas the base represents lowest HPMC fraction (i.e. 50%), with PEG6000 and poloxamer407 at their higher fractions, respectively at left and right points of the base. As seen, e.g. in the contour plot of release%45 min, the higher values of the response were observed where the fractions of HPMCE5, PEG6000, and poloxamer407 were at higher, lower, and close to middle values used in the SE formulations.

Bottom Line: A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE.The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances.As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Novel Drug Delivery Systems Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.

No MeSH data available.


Related in: MedlinePlus