emilyrk39+One+Page+Summary

Emily Krantz Chem 367 Article Summary

Diclofenac Soluility: Independent Determination of the Intrinsic Solubility of Three Crystal Forms
=Introduction:= There are many different types and definitions of solubility and it is hard to measure them accurately thus there are many measurements on solubility in literature that differ dramatically.

=Results and Discussion:= Diclofenac solubility in water was investigated using precisely controlled experimental procedures using 3 forms: anhydrous sodium salt, 4.75 hydrate sodium salt and the anhyfrous free acid.

An intrinsic solubility determination was used based on ‘potentio-metric acid-base titration’, which is a process carried out by dissolving a material in water and partially re-precipitating it. Cheqsol program was used taking the data and displaying it on a screen. The solution is changed from sub-saturated to supersaturated until the value for the transition shows itself in the data. The experiment was repeated 10 times.

Sigma-Aldrich ({2-[(2,6-dichlorophenyl)amino]- phenyl}acetic acid)) was dissolved in ethanol left in a room for a week until crystal appeared. The difference from pentahydrate is in the arrangement of sodium ion and water molecules. X ray diffraction showed the crystal was a hydrate with 4 diclofenac anions, 4 sodium cations and nineteen water molecules. The water molecules became ordered suggesting a new crystal form with 5 % less water and a higher R factor.

X-ray powder experiments distinguished between re-crystallized diclofenac and the commercial sample. Thermogravimetric analysis showed the commercial sample had a melting point of 284.3 and the re-crystallized had a melting point of 263.38. Titrations were performed at difference concentrations of the cosolvent and extrapolation to zero of the co-solvent at .15M ionic strength and 25C.

The results showed agreement between the transition point from supersaturation to sub-saturation. If the crossing points lie close to eachother the system is in equilibrium, if they are far apart they need more time to evolve toward the steady state.

Neutral diclofenac was isolated after 8 experiments at pH of 6.5. Differential scanning calorimetry, thermogravimetric analysis and powder x-ray diffraction chaterorgized the sample to a structure of SIKL10H01 with a melting point of 180.5.

The results of the experiment that was carried out 10 times and showed an agreement between the different forms of diclofenac and shows that intrinsic solubility is independent of the original form of the experiment. Reporting aqueous solubility without pH is confusing because carbonate-saturated water could affect the pH and the solubility.

Aqueous solubility is concentratin of compound when excess solid is presend in a solution that is saturated of pure warer. An equation gives the monoprotic acid aqueous solubility. Using the mean solubility at a pH of 7 the solubility in water was found to be 857.7 ug mL^-1. Consistent conditions for repeating the runs were used. The kinetic solubilities, a measure of the ability of the compound to form supersaturated solutions, were much laeer than intrinsic solubilities. The kinetic values were distint with variances in the mean values much larger than the standard deviations.

=Experimental Section= GLpKa titrator and D=Pas spectrometer were used with Cheqsol software in a .15 M KCl solution in a Ni atmosphere using .5M KCl and .5M KOH.

Metler Toledo DSC 821 differential scanning caloimeter was used with 5-10 mg of each sample sealed in an pan with a hold pierced in the lid that was made out of aluminum.

Metler MT5 was used for thermogravimetric analysis using STAR software.

A sample with .7mm diameter borosilicate capillary was used in a stoe- stadi -=diffractometer operating in debye-scherrer geometry at 290 K and counting over a 24 hour period.

Perfluoropolyether oil was used to immerse the single crystals mounted on glass fibers and placed in a low temperature N stream. Nonius Kappa CCD diffractometer was used to exame the crystals using a thin slice K and omega scans at 150K utilizing

Mo and Ka radiation. SORTA V was used to correct the data and SHELXTL software was used to solve directly.

http://pubs.acs.org/doi/abs/10.1021/jm0612970