Dissolving veterinary medicinal products correctly is essential for a good effectivity. Solubility problems can have several causes, one of which is too low of a concentration. This article will give you more insight in the occurrence of this problem and means to prevent it.
Calculating the dosage of drinking water medication is more and more based upon the dosage of the active ingredient in milligram per kilogram body weight and the daily water intake. This is a positive trend because this method is more accurate than the use of a set drinking water dosage per 1000 liters of drinking water. In specific situations this method of drinking water medication administration can however result in solubility problems due to a low concentration of the active ingredient.
What is the cause of these problems?
In animals that drink a relative large amount of water such as young chickens, a relatively large amount of water has to be used to prepare the pre-solution. As a result, the concentration of the active ingredient in both the pre- and end-solution is low. It is this concentration that can be critical for the solubility. Most veterinary medicinal products will dissolve only at a high or low pH.
Which products pose a risk?
In practice problems are encountered especially with products that dissolve at a high pH. Some examples are:
- Toltrazuril (Dozuril®)
- Enrofloxacin
- Flumequine (Flumequine WSP)
- Amoxicillin (Amoxy Active®, Amoxycillin WS)
- Trimethoprim and Sulfonamide combinations (T.S.Sol®)
Problems caused by a low concentration can also occur with products that dissolve in an acidic environment. The most important category here is the group of tetracyclines such as doxycycline and oxytetracycline.
What does Dopharma do to prevent these problems?
When new products are developed Dopharma will always try to adjust the composition in such a way that solubility problems in the field are prevented. Sometimes this is achieved by adding specific excipients to the product. The amount of added excipients is however often limited because of the amount of active ingredient in the product. When it is then necessary to dilute this product a lot, the concentration of the excipient in the solution might become too low to positively influence the solubility.
Besides adjusting the composition of the product, Dopharma also provides water conditioners. These products change the pH of the pre-solution. When these products are applied correctly, they can improve the solubility and sometimes the stability of the veterinary medicinal products in a solution.
For products that dissolve in an alkaline environment we provide Metasol or Dozuril® diluent. Dozuril® diluent does not only increase the pH, but also binds to cations like calcium and magnesium. As a result these ions cannot form complexes with the medicinal products.
For active ingredients that dissolve in an acidic environment, such as tetracyclines, WpH corrector can be used. This will, like the Dozuril® diluent, also bind ions.
The concentration of water conditioner needed depends on the product and the characteristics of the drinking water.
What can you as veterinarian or farmer do to prevent these problems?
Of course you can use the water conditioners that are provided. There are however also other ways to prevent problems. The water quality of the drinking water used to dissolve the products in is very important and can play an important role in the prevention of solubility problems. Water from an own source can have a different hardness or pH than tap water and can therefore pose a higher risk of precipitation. Also contamination of the pipes or buckets, as well as leaving solutions uncovered, can predispose to the occurrence of precipitation.
You can take the following measures to prevent problems:
- Use only tap water when the animals need to be medicated.
- Use only clean materials to dissolve the veterinary medicinal products.
- Make sure the pipelines of the drinking water system are clean before the treatment is initiated.
- Change the percentage of the dosing equipment in such a way that the concentration of the veterinary medicine in the pre-solution can be increased. When a lower percentage is used, less water is needed to prepare the pre-solution.
- Apply pulse dosing when appropriate. In this case the products are not given continuously throughout the day, but during specific time frames, e.g. several hours in the morning and several hours in the late afternoon. This method is only applicable to the antibiotics for which it is not necessary to achieve continuous plasma concentrations. These are the antibiotics with a concentration dependent mode of action such as the fluoroquinolones (enrofloxacin and flumequine). For antibiotics with a time dependent mode of action, such as penicillins and trimethoprim/sulfonamide combinations, this method is less suitable.
As a guideline the following concentrations of veterinary medicinal products can be used. Under normal circumstances these concentrations should not result in solubility problems. When lower concentrations are needed, consider the above mentioned measures.
| Product | Minimal concentration in the pre-solution |
| Flumequine 50% | 100 gram / 10 L water |
| Amoxy Active® 131 mg/g | 500 gram / 10 L water |
| T.S.-Sol® | 3 L / 10 L water |
Finally, it is always important to keep in mind that any administration not mentioned in the SPC should be considered off-label use.
