Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change

Figures & data

Table 1.  Aqueous solubility of flurbiprofen.

Carrier	Drug solubility (μg/ml)
Water	5.1 ± 0.2
Hydrophilic polymers^a
Sodium carboxymethyl cellulose	3,954.0 ± 116.9
Polyvinylpyrrolidone	3.5 ± 3.1
Hydrooxypropyl cellulose	11.3 ± 0.3
Hydroxypropylmethyl cellulose	44.1 ± 2.7
Surfactants^b
Polyethylene glycol 6000	71.2 ± 22.1
Polyethylene glycol 4000	46.3 ± 9.4
Poloxamer 188	487.0 ± 251.5
Poloxamer 407	2,351.0 ± 548.4
Labrafil M 1994	328.3 ± 1.4
Labrafil M 2125	428.2 ± 262.2
Span 20	496.8 ± 81.7
Span 80	553.5 ± 21.3
Tween 20	8,735.1 ± 1220.6
Tween 80	11,193.2 ± 3074.9

^a Each value means the solubility of flurbiprofen in the distilled water containing 1% hydrophilic polymer.

^b Each value means the solubility of flurbiprofen in the distilled water containing 10% surfactant.

Each value represents the mean ± SE (n = 3).

Table 2.  Compositions of flurbiprofen-loaded solid dispersions.

Ingredients (g)	I	II	III	IV	V	VI	VII
Flurbiprofen	6	6	6	6	6	6	6
Na-CMC	3	2.5	2	1.5	0.625	1.25	5
Tween 80	0	0.5	1	1.5	0.125	0.25	1

Figure 1.  Effect of solid dispersions on the solubility of flurbiprofen. Each value represents the mean ± SD (n = 3). The flurbiprofen-loaded solid dispersion was composed of flurbiprofen/Na-CMC/Tween 80.

Figure 2.  Effect of solid dispersions on the dissolution of flurbiprofen. Each value represents the mean ± SD (n = 6). The flurbiprofen-loaded solid dispersion was composed of flurbiprofen/Na-CMC/Tween 80.

Figure 3.  Scanning electron micrographs: (a) flurbiprofen powder (×800); (b) flurbiprofen-loaded solid dispersion (×250).

Figure 4.  Differential scanning calorimetric thermograms: (a) flurbiprofen powder; (b) solid dispersion; (c) physical mixture; (d) Na-CMC.

Figure 5.  X-ray powder diffraction: (a) flurbiprofen powder; (b) physical mixture; (c) solid dispersion.

Figure 6.  Dissolution profile of drug from solid dispersion and commercial product. Each value represents the mean ± SD (n = 6). * p < 0.05 compared with commercial product.

Figure 7.  Plasma concentration-time profiles of drug after oral administration of solid dispersion and commercial product to rats. Each value represents the mean ± SD (n = 6). * p < 0.05 compared with commercial product.

Table 3.  Pharmacokinetic parameters.

Parameters	Commercial product	Solid dispersion
Cmax (μg/ml)	27.56 ± 2.57	36.43 ± 5.15*
Tmax (h)	0.5 ± 0.0	1.6 ± 0.55*
AUC (h· μg/ml)	228.30 ± 16.74	345.09 ± 41.93*
t1/2 (h)	9.35 ± 2.23	7.26 ± 3.77
Kel (h^−1)	0.07 ± 0.02	0.06 ± 0.04

Each value represents the mean ± SD (n = 6).

* p < 0.05 compared with commercial product.