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Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design.

Madgulkar AR, Bhalekar MR, Padalkar RR, Shaikh MY - J Pharm (Cairo) (2012)

Bottom Line: The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours.The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05).The statistical models developed for optimization were found to be valid.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Pune 411001, Maharashtra, India.

ABSTRACT
The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X 1), HPMC K100M (X 2), and dicalcium phosphate (X 3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y 1) and at 8th hour (Y 2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid.

No MeSH data available.


Related in: MedlinePlus

Contour plot showing amount of drug release at second hour (Y1) using different combinatinon, of X1, X2, and X3. The contour lines showing percentage of drug release at the end of second hour.
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fig6: Contour plot showing amount of drug release at second hour (Y1) using different combinatinon, of X1, X2, and X3. The contour lines showing percentage of drug release at the end of second hour.

Mentions: To demonstrate graphically the effect of release modifying polymers on the dissolution profile, contour plots and 3D graphs were generated. The 3D graph (as shown in Figure 6(a)) for rel2 Hr shows that percent drug release at second hour is plotted on y-axis where as the concentrations of excipients were plotted on x- and z-axis. As the concentration of carboxymethyl xyloglucan and HPMC K100M increased from 180 to 200 mg and 10 to 30 mg, respectively, the percent drug release decreased signifying that the polymers have definite effect on drug release, and especially along the axis region of HPMC-K-100M the effect was greater at lower concentration which indicate its effectiveness in controlling burst release is prominent at lower level, whereas the increasing concentration of DCP shows significant effect on drug release at lowest concentration. The contour plot (as shown in Figure 6(b)) for rel2  Hr justifies that optimum formulation complying with the acceptance criteria can be achieved by selecting the formulations near to the upper left side of the triangle-shaped contour plot which is the diagram obtained from the evaluation result of (F1–F7) formulations. Almost similar results were observed with 3D graph (as shown in Figure 7(a)) and contour plot (as shown in Figure 7(b)) for rel8 Hr. Here as the concentration of carboxymethyl xyloglucan increased release retardation effect, also increases due to increase in the diffusion path length and DCP is showing its effect at lower concentration but not at higher concentration, while HPMC-K-100 M is helping to control burst release in initial hours but not showing any release retarding effect at eight hour because it is used in a smaller quantity.


Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design.

Madgulkar AR, Bhalekar MR, Padalkar RR, Shaikh MY - J Pharm (Cairo) (2012)

Contour plot showing amount of drug release at second hour (Y1) using different combinatinon, of X1, X2, and X3. The contour lines showing percentage of drug release at the end of second hour.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4595968&req=5

fig6: Contour plot showing amount of drug release at second hour (Y1) using different combinatinon, of X1, X2, and X3. The contour lines showing percentage of drug release at the end of second hour.
Mentions: To demonstrate graphically the effect of release modifying polymers on the dissolution profile, contour plots and 3D graphs were generated. The 3D graph (as shown in Figure 6(a)) for rel2 Hr shows that percent drug release at second hour is plotted on y-axis where as the concentrations of excipients were plotted on x- and z-axis. As the concentration of carboxymethyl xyloglucan and HPMC K100M increased from 180 to 200 mg and 10 to 30 mg, respectively, the percent drug release decreased signifying that the polymers have definite effect on drug release, and especially along the axis region of HPMC-K-100M the effect was greater at lower concentration which indicate its effectiveness in controlling burst release is prominent at lower level, whereas the increasing concentration of DCP shows significant effect on drug release at lowest concentration. The contour plot (as shown in Figure 6(b)) for rel2  Hr justifies that optimum formulation complying with the acceptance criteria can be achieved by selecting the formulations near to the upper left side of the triangle-shaped contour plot which is the diagram obtained from the evaluation result of (F1–F7) formulations. Almost similar results were observed with 3D graph (as shown in Figure 7(a)) and contour plot (as shown in Figure 7(b)) for rel8 Hr. Here as the concentration of carboxymethyl xyloglucan increased release retardation effect, also increases due to increase in the diffusion path length and DCP is showing its effect at lower concentration but not at higher concentration, while HPMC-K-100 M is helping to control burst release in initial hours but not showing any release retarding effect at eight hour because it is used in a smaller quantity.

Bottom Line: The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours.The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05).The statistical models developed for optimization were found to be valid.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Pune 411001, Maharashtra, India.

ABSTRACT
The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X 1), HPMC K100M (X 2), and dicalcium phosphate (X 3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y 1) and at 8th hour (Y 2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid.

No MeSH data available.


Related in: MedlinePlus