Limits...
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 desirability, based on the criteria of maximal release%45 min and dissolution efficiency in 2 h and minimal mean dissolution time for glibenclamide formulations prepared by the SE (top) and SCF (bottom) techniques. The carrier systems were composed of varied fractions of HPMCE5, PEG6000, and Poloxamer407, where H+P+X=100% (10).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4318002&req=5

Figure 9: The contour plots of desirability, based on the criteria of maximal release%45 min and dissolution efficiency in 2 h and minimal mean dissolution time for glibenclamide formulations prepared by the SE (top) and SCF (bottom) techniques. The carrier systems were composed of varied fractions of HPMCE5, PEG6000, and Poloxamer407, where H+P+X=100% (10).

Mentions: Fig. 8 indicates the effects of different variables (two components) on the dissolution parameters of the formulations prepared by the SCF-SAS technique. For example, the higher values of the release%45 min were observed where PEG6000 and poloxamer407 fractions used were at almost highest and lower to middle values, respectively. The HPMCE5 fraction was fixed at 60% in all formulations. A numerical optimization technique was used to set desired goals for each response and generate optimal conditions using the desirability approach. A constraint to maximizing release%45 min and DE and minimizing the MDT was to set the goal to indicate the optimal weight ranges of formulation variables based on the criterion of desirability. Fig. 9 represents contour plots of desirability for GLIB formulations prepared by SE and SCF technique. The upper plot indicate that SE formulations comprising lower HPMC, higher PEG and lower to middle poloxamer amounts produced lower MDT, higher DE2%, and higher release%45 min. To evaluate the optimization capability of the model generated according to the results of the D-optimal mixture design, an optimized GLIB formulation comprising HPMC (50%), PEG (40%), and poloxamer (10%) as carrier system, was prepared, its dissolution performance was studied and DE2% and release%45 min were calculated. The observed responses, as compared to the predicted responses by the model, are given in Table 5. The optimized GLIB formulation showed release%45 min of 81.2% and DE2% of 73.1, both close to the values predicted by the model, with small error values (−1% and 2.4%, respectively). In formulations prepared by SCF, where HPMC level was fixed at 60%, greater values of desirability of two-component mixtures were similarly located in regions of higher PEG levels (i.e. 34%) and lower to middle levels of poloxamer (i.e. 6%).


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 desirability, based on the criteria of maximal release%45 min and dissolution efficiency in 2 h and minimal mean dissolution time for glibenclamide formulations prepared by the SE (top) and SCF (bottom) techniques. The carrier systems were composed of varied fractions of HPMCE5, PEG6000, and Poloxamer407, where H+P+X=100% (10).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: The contour plots of desirability, based on the criteria of maximal release%45 min and dissolution efficiency in 2 h and minimal mean dissolution time for glibenclamide formulations prepared by the SE (top) and SCF (bottom) techniques. The carrier systems were composed of varied fractions of HPMCE5, PEG6000, and Poloxamer407, where H+P+X=100% (10).
Mentions: Fig. 8 indicates the effects of different variables (two components) on the dissolution parameters of the formulations prepared by the SCF-SAS technique. For example, the higher values of the release%45 min were observed where PEG6000 and poloxamer407 fractions used were at almost highest and lower to middle values, respectively. The HPMCE5 fraction was fixed at 60% in all formulations. A numerical optimization technique was used to set desired goals for each response and generate optimal conditions using the desirability approach. A constraint to maximizing release%45 min and DE and minimizing the MDT was to set the goal to indicate the optimal weight ranges of formulation variables based on the criterion of desirability. Fig. 9 represents contour plots of desirability for GLIB formulations prepared by SE and SCF technique. The upper plot indicate that SE formulations comprising lower HPMC, higher PEG and lower to middle poloxamer amounts produced lower MDT, higher DE2%, and higher release%45 min. To evaluate the optimization capability of the model generated according to the results of the D-optimal mixture design, an optimized GLIB formulation comprising HPMC (50%), PEG (40%), and poloxamer (10%) as carrier system, was prepared, its dissolution performance was studied and DE2% and release%45 min were calculated. The observed responses, as compared to the predicted responses by the model, are given in Table 5. The optimized GLIB formulation showed release%45 min of 81.2% and DE2% of 73.1, both close to the values predicted by the model, with small error values (−1% and 2.4%, respectively). In formulations prepared by SCF, where HPMC level was fixed at 60%, greater values of desirability of two-component mixtures were similarly located in regions of higher PEG levels (i.e. 34%) and lower to middle levels of poloxamer (i.e. 6%).

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