5 to 6.9. The test was performed by transferring 750 mL of gastric juice (pH 1.5) to six dissolution vessels and allowing the temperature to stabilize at 37.0 ± 0.5°C. One tablet was placed in each rotating basket within each vessel to begin the dissolution test at 50 rpm. After 1 hour, a 200 mL sample was removed from each of the six dissolution vessels and accurately measured, and 20 mL of sulfuric acid 1 M was added.

To quantify the amount of iron released, this sample was then titrated with a solution of cerium ammonium sulfate 0.01 M, using a platinum electrode as the indicator electrode and PF-6463922 chemical structure mercury as a reference electrode.[18] selleck screening library The remainder of the medium in the dissolution vessel was then discarded and replaced with intestinal juice pH 4.5, which was allowed to stabilize to 37.0 ± 0.5°C for 5 minutes, and the test proceeded MS-275 mouse for a further 1-hour rotation period to allow further dissolution of the tablet.

After 1 hour, another 200 mL sample was then taken from each vessel and measured precisely, and 20 mL of sulfuric acid 1 M was added. This was then titrated with a solution of cerium ammonium sulfate 0.01 M, using a platinum electrode as the indicator electrode and mercury as a reference electrode. The procedure was then repeated using intestinal juice with a pH of 6.9 Tyrosine-protein kinase BLK and a rotation period of 2 hours. These conditions were established in order to have a minimum of three timepoints, covering the early, middle

and late stages of the dissolution profile, with the last timepoint corresponding to the plateau of the dissolution profile.[19] Moreover, these three timepoints are sufficient to draw a dissolution profile that can be used to compare the different formulas. The experimental method was validated as per the International Conference on Harmonisation (ICH) guideline Q2[20] and the United States Pharmacopeia.[16] Linearity was assessed for the three pHs by plotting three calibration plots, with a correlation coefficient of 1.0000. Repeatability and intermediate precision were assessed by analyzing two sets of six tablets on different days, with different analysts. The overall relative standard deviation was less than 10% as per the validation protocol for the three dissolution media, while the absolute difference between mean dissolution values for each pH was less than 10%. Accuracy was evaluated for each pH by spiking placebo with known amounts of iron (II). A mean recovery index within 100 ± 2% was obtained for the three dissolution media. Robustness was evaluated by changing the critical parameters of the method. The results obtained were within 100 ± 5% of the results obtained under standard conditions.