Precautions for dissolution experiment

Prepare dissolution medium
The gas dissolved in the dissolution medium may interfere with the reproducibility of the dissolution results. Therefore, before preparing the dissolution medium, specific methods for degassing the purified water include ultrasound, boiling, heating to 41 ℃, and vacuum degassing. If using the method of heating and degassing, it is necessary to wait until the degassing is completed and the water temperature drops to room temperature before preparing, in order to avoid the addition of hydrochloric acid or acetic acid, which will evaporate due to heat and affect the pH value of the dissolution medium. The pH value of purified water from different sources varies. When using purified water as the dissolution medium, it is best to determine the pH value of the water before use to avoid changes in dissolution data caused by different pH values of the water.
Install the mixing blade (basket)
Mechanical verification is required during the factory and installation of the dissolution apparatus (or every 6 months). During the use process after verification, if the installation position of the stirring blade (basket) is different from that during verification, it will affect the coaxiality between the stirring blade (basket) and the dissolution cup, thereby affecting the flow state of the dissolution medium in the dissolution cup and causing changes in the dissolution data of the sample.
In addition, some manufacturers' dissolution testers require adjusting the installation height of the stirring blade (basket), but often for the convenience of future use, we do not remove the stirring blade (basket) when cleaning the equipment, thinking that the stirring blade (basket) height has been adjusted and does not need to be adjusted again. However, during use, the shaking of the mixing blade (basket) may cause the fixed mixing blade (basket) to loosen. After prolonged use, the height of the stirring blade (basket) may have decreased, ultimately leading to changes in the solubility of the sample or a decrease in the parallelism of dissolution within the group. When using the basket rotation method for testing, attention should be paid to the cleanliness of the basket and whether the gaps in the basket are blocked. If blocked, ultrasonic treatment or boiling in dilute nitric acid and then boiling in water can be used to clean it, otherwise it will affect the accuracy of the dissolution data. At the same time, attention should also be paid to whether the shape of the rotating basket is complete. If it is twisted or deformed, a new rotating basket should be replaced in a timely manner
Install dissolution cup
The dissolution cup has different numbers like the stirring paddle (basket). The dissolution cup should also be installed in the corresponding position during use. In addition to matching the number of the dissolution cup, after the dissolution instrument has passed the verification of perpendicularity and coaxiality, the positions where the upper edge of the dissolution cup is connected to the fixing device are marked. For example: vertical lines, arrows. Therefore, when conducting dissolution tests, each basket shaft, paddle, and dissolution cup should be placed in the original validated position, keeping the relative position of each dissolution cup to the fixture unchanged. However, when installing a dissolution apparatus, people often overlook this point, causing the axis of the dissolution cup to not coincide with the axis of the stirring blade, thereby changing the flow state of the dissolution medium in the dissolution cup and causing changes in the dissolution data.
Install filter head
Nowadays, dissolution testers are generally fully automatic or semi-automatic sampling devices. At the sampling end of the automatic dissolution tester, a filter head must be installed. If a filter head is not installed at the sampling end of the sampling needle, undissolved sample particles will enter the instrument pipeline with the sampling solution. On the one hand, undissolved particles may block the pipeline, making the instrument's sampling volume inaccurate; On the other hand, because there is usually a 2-5 minute interval between the transfer of the sample from the sampling end to the test tube (depending on the sampling amount), undissolved particles will continue to dissolve when transferred in the pipeline, which will affect the accuracy of measurement or final dissolution. After the experiment is completed, the used filter head should be sonicated in the solvent for 20-30 minutes and then cleaned with purified water ultrasonically. It should not be soaked in the dissolution medium alone and rinsed with clean water. Because this method cannot clean the filter head thoroughly, it will affect the next use.
Sample location
When conducting dissolution experiments, the position of the sample should be at a specific location on the dissolution cup. For example, in the paddle method, the samples should be placed at the bottom of the dissolution cup, directly below the paddle. If some tablets stick to the wall after administration, it will cause a larger RSD of the dissolution test results and an increase in the dissolution rate of the sample. Therefore, during the dissolution test, attention should also be paid to observing whether the position of the sample in the dissolution cup is reasonable (or the same) after each sample injection
Dissolution phenomenon
The results of dissolution tests are not limited to dissolution data. When examining or comparing dissolution curves, people only pay attention to dissolution data and ignore the observation of dissolution phenomena. In fact, the dissolution phenomenon has guiding significance for the prescription analysis of original formulations and the adjustment of prescription processes for homemade formulations.
The disintegration phenomena of the original development agent include dissolution type (possibly with a high content of lactose in the prescription), expansion type disintegration, and "smoking" phenomenon (possibly with a high content of microcrystalline cellulose in the prescription); Does the tablet form sand dunes at the bottom of the cup after disintegration. Similarly, the originally developed particles remain in powder form after disintegration. Is the coating film of microspheres swollen or dissolved, and does the microsphere expand during the dissolution process.
Water bath height
The water in the peripheral water tank of the dissolution instrument will also evaporate due to heating, causing the liquid level in the water tank to drop. If the height of the water bath around the dissolution instrument is lower than the liquid level of the dissolution medium in the dissolution cup, it will affect the temperature of the dissolution solution in the dissolution cup, causing a change in the dissolution degree of the sample and affecting the dissolution results. Therefore, when conducting dissolution tests, attention should be paid to the height of the water bath around the dissolution apparatus.
surrounding environment
The shaking of the stirring blade (basket) of the dissolution apparatus will affect the coaxiality between the stirring blade (basket) and the dissolution cup. The shaking of the agitator (basket) is caused by both the instrument's own factors and the surrounding environment, such as centrifugal machines, vortex machines, vacuum pumps, etc., which can also cause the agitator (basket) to shake. Therefore, during the dissolution experiment, try to minimize the influence of other equipment on the dissolution apparatus.
Conclusion
In addition, during the dissolution test, attention should also be paid to other factors such as the height of the sampling needle, the speed of the stirring blade (basket), and the actual temperature of the dissolution medium. When comparing the dissolution curves of the original formulation and the self-made product, it is not only the differences in the formulation process that cause the dissolution curves to be inconsistent. Attention should be paid to the influence of various details in the experiment on the dissolution results.