Erlir Majko, ARL Senior Chemist
Certain Active Pharmaceutical Ingredients (APIs), like Vancomycin, Naltrexone, and Dexamethasone Sodium Phosphate can be hygroscopic. Water molecules are attracted and held by the APIs by either absorption or adsorption from the surrounding environment. This issue is exacerbated in humid conditions. The water content of each API should be listed in the manufacturer's Certificate of Analysis (CofA). When compounding a drug, the water content should be accounted for in the final calculations to ensure that the finished product is not sub-potent.
Certain APIs tend to be very hygroscopic and may have water contents up to 50% and may increase over time. If potency results start to gradually test lower than the expected amount but the compounding process has not changed, it could be an indicator that the starting material may have absorbed water. In this case ARL suggests testing the water content regularly to ensure accuracy when compounding. The more often the API is used, the higher the probability that the API will absorb water. Starting materials stored in refrigerated conditions should be allowed to come at room temperature prior to use. For starting materials stored in the freezer, it may take longer for the starting material to come at room temperature. This ensures there is no temperature difference between the room temperature and the temperature inside the starting material container. If the starting material is not allowed to come at room temperature with the cap on the bottle, then the difference in temperature between the material container and the ambient temperature may increase water absorption due to temperature difference. The container of the starting material can also be stored in a desiccator to help keep the material dry.
When calculating how much starting material to use when compounding, the water content must be taken into account in addition to the purity of the material. These values are usually listed in the CofA. For example, if a starting material has a water content of 4.5%, and an assay value of 99.8%, then the as-is purity of the starting material can be calculated as follows (100-4.5)*0.998/100 = 0.953.
The inverse of this number will give an adjustment factor for the API weight (e.g. 1/0.953 = 1.049).The adjustment factor is used to determine how much starting material is to be used to correct for the water content. In some cases (e.g. Naltrexone HCl), the total solvent value must be used, instead of the water content value, as per USP monograph.
For more articles on potency, please visit our Educational Center.