Limit of solubility reported

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Limit of solubility
Solution used
References
Water
Temperature
°C
RT
2.55 ± 0.12 μg/ml = 6.68 μM
3 to 7 μg/ml= 7.9 to 18.35 μM
Aqueous solution pH 7
40°C
[2,3,4]
6 μg/mL = 15.7 μM
Glycine/NaOH pH 7.6
25°C
[5]
7 μg/mL = 18.4 μM
Water
14 μg/mL = 33 μM
Glycine/NaOH pH 9.2
0.015 μg/mL = 39 μM
80% Water / 20% ethanol
About 1 μg/mL = 2.6 μM
Water,
NR
[6]
About 5 μg/mL= 13.1 μM
Aqueous solutions pH<9,
5 to 40°C
[7]
3.3 mg/L= 8,7 μM
Water
25
[8-9]
5.03 mg/L = 13.2 μM
Water (predicted solubility)
Between 10 and 12.5 μM
Water
Between 5 and 7.5 μM
Cell culture media* pH 7.3-7.4
Between 7.5 and 10 μM
Cell culture media* pH 7.3-7.4, 0.5% serum
Between 17.5 and 20 μM
Cell culture media* pH 7.3-7.4, 10% serum
Between 18 and 22 μM
Cell culture media* pH 9.2, 0.5% serum
Between 5 and 7.5μM
Cell culture media* pH 6, 0.5% serum
Between 100 and 160 μM
Pure serum (FCS)
> 18 μM
Cell culture media*, 0.5 % serum, 10%
[1]
[8-10]
33 to 37°C
Present work
solvents**
> 40 μM
Cell culture media, 0.5 % serum, 20%
solvents**
Table S1. Comparison of Celecoxib solubility reported in the literature and determined in the
present work. When the solubility is calculated by diluting Celecoxib from a DMSO stock, the final
concentration of DMSO should be taken into account (0.2% in the present work, up to 1% in other
studies).
*Common cell culture media and solutions tested are DMEM, RPMI, RPMI/DMEM, HBSS, PBS. The
presence/absence of NaHCO3, Phenol Red; Hepes does not make a significant difference. ** Solvents tested are
DMSO, Ethanol, Methanol, Aceton, Glycerol. Besides increasing the solubility limit, these solvent visibly reduced
number and dimension of precipitates/crystals at the concentrations of Celecoxib used in the toxicity assays.
References
1. Gupta VR, Mutalik S, Patel MM, Jani GK (2007) Spherical crystals of celecoxib to improve
solubility, dissolution rate and micromeritic properties. Acta Pharm 57: 173-184.
2. Subramanian N, Ghosal SK, Moulik SP (2004) Topical delivery of celecoxib
using
microemulsion. Acta Pol Pharm 61: 335-341.
3. Sinha VR, Anitha R, Ghosh S, Amita, Kumria R, et al. (2007) Physicochemical characterization
and in vitro dissolution behaviour of celecoxib -beta-cyclodextrin inclusion complexes. Acta
Pharm 57: 47-60.
4. Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, et al. (2001) Pharmacokinetics of
celecoxib
after oral administration in dogs and humans: effect of food and site of
absorption. J Pharmacol Exp Ther 297: 638-645.
5. Seedher N, Bhatia S (2003) Solubility enhancement of Cox-2 inhibitors using various solvent
systems. AAPS PharmSciTech 4: E33.
6. Guzman HR, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P (2007) Combined use of
crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib
from solid oral formulations. J Pharm Sci 96: 2686-2702.
7. Datasheet Celebrex (www.celebrex.com)
8. Drugbank. Drug card for Celecoxib (DB00482) (http://www.drugbank.ca/drugs/DB00482)
9. SRC PhysProp Database (http://www.syrres.com/esc/physdemo.htm). Celecoxib , CAS Registry
Number 169590-42-5
10. ALOGPS 2.1 program (http://www.vcclab.org/web/alogps/)
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