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Original Research

Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper–Lin small composite design

Pages 825-839 | Published online: 24 Feb 2016

Figures & data

Table 1 Design matrix including investigated process variables with their levels

Figure 1 Scanning electron photomicrographs of the optimized CTZ microspheres at (A) ×200 magnification, (B) ×300 magnification, (C) ×450 magnification, and (D) ×750 magnification.

Abbreviation: CTZ, cetirizine hydrochloride.
Figure 1 Scanning electron photomicrographs of the optimized CTZ microspheres at (A) ×200 magnification, (B) ×300 magnification, (C) ×450 magnification, and (D) ×750 magnification.

Table 2 Observed values of responses (Y1Y7) for 18 formulations of CTZ-loaded polymethacrylate microspheres

Figure 2 Release profiles of CTZ from the D-LSCD formulations; (A) release profiles for F1–F6, (B) release profiles for F7–F12, and (C) release profiles for F13–F18.

Abbreviations: CTZ, cetirizine hydrochloride; D-LSCD, Draper–Lin small composite design.
Figure 2 Release profiles of CTZ from the D-LSCD formulations; (A) release profiles for F1–F6, (B) release profiles for F7–F12, and (C) release profiles for F13–F18.

Figure 3 Pareto charts of standardized effects on the particle size (A), angle of repose (B), production yield (C), encapsulation efficiency (D), loading capacity (E), initial release (F), and time for 85% of drug release (G).

Abbreviations: HLB, hydrophilic lipophilic balance; ERL, Eudragit RLPO; X1, ERL loading percentage; X2, emulsifier HLB; X3, talc percentage; X4, dispersed phase volume; X1X2, X1X3, X1X4, X2X3, X2X4, and X3X4 are the interaction terms between the factors; X1X1, X2X2, X3X3, and X4X4 are the quadratic terms between the factors.
Figure 3 Pareto charts of standardized effects on the particle size (A), angle of repose (B), production yield (C), encapsulation efficiency (D), loading capacity (E), initial release (F), and time for 85% of drug release (G).

Figure 4 Three-dimensional response surfaces with contour plots below generated from the D-LSCD demonstrating the effect of ERL loading%, emulsifier HLB, talc percentage, and the dispersed phase volume on the particle size (A), angle of repose (B), production yield (C), encapsulation efficiency (D), loading capacity (E), initial release (F), and time for 85% of drug release (G).

Abbreviations: HLB, hydrophilic lipophilic balance; ERL, Eudragit RLPO; D-LSCD, Draper–Lin small composite design; X1, ERLloading percentage; X2, emulsifier HLB; X3, talc percentage; X4, dispersed phase volume; X1X2, X1X3, X1X4, X2X3, X2X4, and X3X4 are the interaction terms between the factors; X1X1, X2X2, X3X3, and X4X4 are the quadratic terms between the factors; Y1, particle size; Y2, angle of repose; Y3, production yield; Y4, encapsulation efficiency; Y5, loading capacity; Y6, initial release; Y7, time for 85% of drug release.
Figure 4 Three-dimensional response surfaces with contour plots below generated from the D-LSCD demonstrating the effect of ERL loading%, emulsifier HLB, talc percentage, and the dispersed phase volume on the particle size (A), angle of repose (B), production yield (C), encapsulation efficiency (D), loading capacity (E), initial release (F), and time for 85% of drug release (G).

Figure 5 Correlations of the factors and responses.

Notes: (A) Correlation between talc% and both particle size and angle of repose, (B) correlation between Eudragit RLPO loading% and both the initial release% and the time for 85% of drug release, (C) correlation between the emulsifier HLB and both the encapsulation efficiency and the loading capacity, and (D) correlation between the dispersed phase volume and both the encapsulation efficiency and the loading capacity.
Abbreviations: HLB, hydrophilic lipophilic balance; ERL, Eudragit RLPO; EE, encapsulation efficiency; LC, loading capacity; T85%, time for 85% of drug release.
Figure 5 Correlations of the factors and responses.

Table 3 Statistical ANOVA of the responses (Y1Y7)

Table 4 Optimum combination of factors, predicted values, observed values, the residuals, and the prediction error percentage for the optimized formulations of CTZ-loaded polymethacrylate microspheres

Table 5 Pharmacokinetic parameters of CTZ following the administration of a single oral dose (10 mg) of the marketed tablets, and the optimized formulation of CTZ microspheres equivalent to 10 mg

Figure 6 Mean plasma concentration–time profiles for CTZ after the oral administration of a single dose (10 mg) of the marketed tablet and the optimized CTZ-loaded polymethacrylate microspheres.

Notes: Data represent the mean value ± standard deviation (n=6); *P<0.05; **P<0.001.
Abbreviation: CTZ, cetirizine hydrochloride.
Figure 6 Mean plasma concentration–time profiles for CTZ after the oral administration of a single dose (10 mg) of the marketed tablet and the optimized CTZ-loaded polymethacrylate microspheres.