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

Response trace plot for the response release%45 min using as reference mixture the centroid of the constrained domain (A: HPMCE5 68%, B: PEG6000 22%, and C: Poloxamer407 10%).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Response trace plot for the response release%45 min using as reference mixture the centroid of the constrained domain (A: HPMCE5 68%, B: PEG6000 22%, and C: Poloxamer407 10%).

Mentions: Dissolution parameters, viz. release%45 min, DE, and MDT, which were calculated for GLIB formulations prepared by the SE and SCF-SAS techniques, are presented in Tables 1 and 2. The effects of formulation variables on these parameters were investigated using Design Expert version 7.1.5. The program provided suitable polynomial equations for the responses investigated as a function of formulation variables and their interactions (Table 3). The model terms for interactions generally exhibited to have higher influences on the responses than each variable alone, as indicated by greater values of their coefficients. The models suggested were analyzed statistically by applying ANOVA (p<0.05) for the responses. Table 4 represents a typical statistical analysis of a response (percent release in 45 min, as an example). In almost all statistical analysis of responses (not shown here), the significant model terms along with insignificant lack of fit and adequate precision were indicated in the analysis of variance test, suggesting suitability of the design used. To better evaluate the contribution of each of the three formulation variables, the response trace method also was used (Fig. 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)

Response trace plot for the response release%45 min using as reference mixture the centroid of the constrained domain (A: HPMCE5 68%, B: PEG6000 22%, and C: Poloxamer407 10%).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Response trace plot for the response release%45 min using as reference mixture the centroid of the constrained domain (A: HPMCE5 68%, B: PEG6000 22%, and C: Poloxamer407 10%).
Mentions: Dissolution parameters, viz. release%45 min, DE, and MDT, which were calculated for GLIB formulations prepared by the SE and SCF-SAS techniques, are presented in Tables 1 and 2. The effects of formulation variables on these parameters were investigated using Design Expert version 7.1.5. The program provided suitable polynomial equations for the responses investigated as a function of formulation variables and their interactions (Table 3). The model terms for interactions generally exhibited to have higher influences on the responses than each variable alone, as indicated by greater values of their coefficients. The models suggested were analyzed statistically by applying ANOVA (p<0.05) for the responses. Table 4 represents a typical statistical analysis of a response (percent release in 45 min, as an example). In almost all statistical analysis of responses (not shown here), the significant model terms along with insignificant lack of fit and adequate precision were indicated in the analysis of variance test, suggesting suitability of the design used. To better evaluate the contribution of each of the three formulation variables, the response trace method also was used (Fig. 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