Colon-targeted celecoxib-loaded Eudragit^® S100-coated poly-ϵ-caprolactone microparticles: Preparation, characterization and in vivo evaluation in rats

Figures & data

Table 1.  A 2³ full factorial design of the prepared PCL single-coat celecoxib-loaded microparticles.

Formulae	PCL M.wt.		Drug: PCL ratio		Span^® 80 concentration
	Low	High	1: 0.5	1: 1	1%, w/v	3%, w/v
F1	+			+	+
F2		+		+	+
F3	+		+		+
F4		+	+		+
F5	+			+		+
F6		+		+		+
F7	+		+			+
F8		+	+			+

Figure 1.  DSC thermograms of celecoxib, PCL, celecoxib: PCL physical mixture and formula F2 (A) and celecoxib, PCL, Eudragit^® S100, celecoxib: PCL: Eudragit^® S100 physical mixture and formula F10 (B).

Figure 2.  X-ray diffractrograms of celecoxib (A), formula F2 (B) and formula F10 (C).

Figure 3.  A. Optical micrographs of PCL single-coat microparticles, formula F2 (A), and double-coat microparticles, formula F10 (B). B. SEM micrographs of PCL single-coat microparticles, formula F2 (C), and double-coat microparticles, formula F10 (D). Scale bar represents 300 μm, X160.

Table 2.  The particle size and the entrapment efficiency % of the prepared celecoxib-loaded microparticles, mean ± S.D., n = 3.

Formulae	Particle size (μm)	Entrapment efficiency (%)
F1	89.26 ± 2.31	87.18 ± 0.08
F2	277.20 ± 6.10	96.54 ± 0.25
F3	81.01 ± 3.04	66.15 ± 0.07
F4	233.51 ± 7.02	67.295 ± 0.41
F5	76.57 ± 2.54	92.20 ± 0.28
F6	237.63 ± 2.27	98.75 ± 0.35
F7	60.66 ± 4.21	70.48 ± 0.67
F8	200.12 ± 6.43	75.15 ± 0.77
F9	51.66 ± 2. 62	68.43 ± 0.68
F10	350.32 ± 7.89	69.8 ± 0.77

Figure 4.  Interaction bar plot representing the effect of PCL M.wt. (low and high), drug: PCL ratio (1:0.5 and 1: 1) and span® 80 concentration (1% and 3%, w/v) on the entrapment efficiency %, mean ± S.D.

Figure 5.  The influence of PCL M.wt. and drug: PCL ratio on in vitro drug release from PCL single-coat microparticles prepared using Span^® 80 (1%, w/v) at 37 ± 0.5 °C (mean ± S.D., n = 3).

Figure 6.  The influence of PCL M.wt. and drug: PCL ratio on in vitro drug release from PCL single-coat microparticles prepared using Span^® 80 (3%, w/v) at 37 ± 0.5 °C (mean ± S.D., n = 3).

Table 3.  Mathematical modeling and release kinetics of celecoxib from the investigated microparticles.

Formulae	Zero order	First order	Higuchi model	Korsmeyer–Peppas model		Order of releas	Mean t50% (h)
	Correlation coefficient (R^2)			Correlation coefficient (R^2)	Release exponent (n)
F1	0.992	0.909	0.993	0.976	0.364	Fickian	0.70
F2	0.920	0.984	0.986	0.988	0.714	Non-Fickian	3.55
F3	0.987	0.949	0.999	0.994	0.291	Fickian	0.26
F4	0.943	0.973	0.986	0.990	0.648	Non-Fickian	1.83
F5	0.988	0.900	0.996	0.987	0.271	Fickian	0.29
F6	0.943	0.966	0.985	0.988	0.694	Non-Fickian	2.42
F7	0.995	0.965	0.999	0.996	0.312	Fickian	0.18
F8	0.956	0.883	0.980	0.983	0.554	Non-Fickian	1.56
F9	0.808	0.697	0.706	0.852	1.109	Super case II	4.43
F10	0.948	0.974	0.946	0.960	0.833	First order	5.37

Figure 7.  Interaction bar plots representing the effect of PCL M.wt. (low and high), drug: PCL ratio (1:0.5 and 1: 1) and Span^® 80 concentration (1% and 3%, w/v) on Q2h (A) and Q4h (B), mean ± S.D.

Figure 8.  In vitro drug release from PCL single-coat microparticles (F2), Eudragit^® S100 single-coat microparticles (F9) and double-coat microparticles (F10) at 37 ± 0.5 °C (mean ± S.D., n = 3).

Table 4.  Pharmacokinetic parameters of celecoxib following oral administration of aqueous suspensions of the best achieved microparticles (Formula F10) and celecoxib powder to rats (mean ± SD, n = 6).

Treatments	Cmax (μg /mL)	Tmax^a (h)	MRT(0-∞) (h)	Ke (h^−1)	t50% (h)	AUC(0-8) (μg h/ml)	AUC(0-∞) (μg h/ml)
Celecoxib powder	3.740 ± 0.367	3	4.106 ± 0.802	0.345 ± 0.105	2.202 ± 0.785	12.795 ± 1.036	14.329 ± 0.844
Formula F10	3.405 ± 0.560	5	6.797 ± 1.604	0.238 ± 0.131	4.023 ± 1.810	14.430 ± 1.728	19.310 ± 1.356

^aMedian

Figure 9.  Plasma concentration–time profiles of celecoxib following oral administration of aqueous suspensions of the best achieved microparticles (F10) and celecoxib powder to fasted rats (mean ± SD, n = 6).