Steroid (Molecular Weight) | Individual Measures | Cocktail Measures: PBSSol (n = 4)b | Measured logD (n = 6)c | Predicted logPd | Mean Particle Size in 1 mg/ml Suspensione | |
---|---|---|---|---|---|---|
OctSol (n = 4)a | PBSSol (n = 4)b | |||||
mg/ml | μg/ml | μg/ml | μm | |||
T (394.43) | 0.29 ± 0.007 | 120.93 ± 19.92 | 129.40 ± 11.84 | 0.71 ± 0.11 | 0.83 | 3.90 ± 0.52 |
P (360.44) | 7.5 ± 0.11 | 302.95 ± 16.94 | 314.40 ± 31.29 | 1.77 ± 0.11 | 1.49 | 0.84 ± 0.03 |
D (392.46) | 3.2 ± 0.33 | 86.70 ± 3.81 | 92.32 ± 5.60 | 1.95 ± 0.02 | 1.87 | 2.51 ± 1.15 |
FA (452.48) | 9.8 ± 0.2 | 17.02 ± 0.64 | 10.17 ± 1.00 | 2.56 ± 0.11 | 2.24 | 4.33 ± 1.50 |
TA (434.49) | 5.2 ± 0.07 | 26.12 ± 6.02 | 14.81 ± 2.00 | 2.58 ± 0.03 | 2.50 | 1.45 ± 0.21 |
B (430.50) | 17.2 ± 0.98 | 23.51 ± 1.08 | 5.72 ± 1.20 | 2.97 ± 0.09 | 3.14 | 2.89 ± 0.87 |
↵a Represents solubility of individual corticosteroid in octanol (OctSol). Excess material was added to the octanol at 37°C and the concentration of the dissolved material was determined using a UV spectrophotometer at the end of 24 h. The rank order for octanol solubility measurements on the basis of one-way ANOVA (multiple comparisons) was B > FA > P > TA > D > T (p < 0.05).
↵b Represents solubility of individual corticosteroid in phosphate-buffered saline, pH 7.4 (PBSSol). Excess material was added to PBS at 37°C, and the concentration of the dissolved material was determined using LC-MS/MS at the end of 24 h. The rank order for independent and cocktail solubility measurements on the basis of one-way ANOVA (multiple comparisons) was P > T > D > FA ∼ TA ∼ B (p < 0.05). Individual solubility values of fluocinolone acetonide, triamcinolone acetonide, and budesonide were significantly higher (p < 0.05, Student's t test) than their solubility values in the cocktail.
↵c Distribution coefficient (D) was measured using the USP shake flask method as reported previously (Thakur et al., 2010). The rank order for logD was B > TA ∼ FA > D ∼ P > T (p < 0.05).
↵d Predicted partition coefficient (P) was obtained from SciFinder Scholar 2007 software.
↵e Particle size was determined for 1 mg/ml suspension of each corticosteroid using Zetasizer Nano (Malvern Instruments Ltd., Malvern, Worcestershire, UK). Rank order for the particle size was FA ∼ T ∼ B > TA > P (particle size of D was significantly different from that of P but not other corticosteroids).