Methods for Measuring Dissolution
The diagram shows a typical GI Dissolution experiment for sample introduced as a powder. Most experiments start at pH 1.8 to simulate conditions in the human stomach. After 30 minutes the pH is raised to 3.8. Other reagents (e.g. FaSSIF, FeSSIF or solubility-enhancing excipients) may also be introduced at this stage. A GI Dissolution Profile is produced after the full experiment is complete. See Sirius inForm Application Note 404 for example of automatic introduction of sample as a tablet, and of pH gradient adjustment.
The profile below shows dissolution of Piroxicam, a molecule with one basic pKa 1.87 and one acidic pKa 5.29. The sample was introduced as a tablet weighing 15 mg. The pH was raised at successive time intervals as shown in the graph. Some dissolution occurred at pH 1.8 because a proportion of the base was in charged form. Dissolution was slowest at pH 3.9 where the molecule was neutral. Dissolution was fastest at pH 7.3 where the molecule was charged.
This profile below shows dissolution of Niflumic acid, a molecule with one basic pKa 2.02 and one acidic pKa 4.84. In these two experiments pellets weighing 17 mg were dissolved in 45 mL of aqueous buffer solution at pH 1.8. One experiment continued under aqueous conditions at higher pH. In the other experiment, an aliquot of FaSSIF solution was added at pH 3.9. The profile shows a rapid increase in the weight dissolving at the time FaSSIF is introduced, but with no increase in the rates of dissolution at higher pH. See Sirius inForm Application Note 404 for another example of dissolution in presence of biorelevant medium.
See Sirius inForm Application Note 404 for another example of dissolution in presence of biorelevant medium.
These profiles compare GI Dissolution and biphasic dissolution. The diagram shows dissolution of Dipyridamole, a basic molecule with pKas of 0.85 and 6.24 Tablets weighing 7.8 mg were dissolved in aqueous buffer solution at pH 1.8. One experiment proceeded under aqueous conditions over the entire pH range; all the Dipyridamole dissolved at pH 1.8 and remained in solution at pH 3.9, but precipitated rapidly at pH 5.4. In the other experiment, 2.5 mL of a lipid, Nonanol, was added at pH 3.9. From the start, Dipyridamole partitioned into the lipid phase and did not precipitate at pH 5.4. See Applications Note 401 for more information about biphasic dissolution.
FaSSIF and FeSSIF measurements are made using simulated intestinal fluids (SIF) provided using SIF POWDERS by biorelevant.com.