Why are drugs mixed with their sodium salts?

Question

I have come across quite a few drugs that are of the form $\ce{HA + NaA}$, where $\ce{A}$ is your target organic compound. A few examples of this are:

• Carmicide which is a mixture of Sodium Citrate and Citric Acid
• Fucidin which is a mixture of Sodium Fusidate and Fusidic Acid

What advantages are there in conjugating a drug with its sodium salt? A similar question says that this increases solubility and also makes the drug easier to crystallize and purify. I'm assuming that the same reasoning does not work for organic acids, considering they will dissolve/ionize quite easily. Please clarify and provide further insight into this topic.

Answer 1

A large percentage of pharmaceuticals are sold as salts, and sometimes even as co-crystals, i.e. a drug cation and a drug anion. You are right in the sense that the basic purpose is to make them soluble but this is not the only one. If it is a intravenous drug, salt form may have less pain. A low molecular weight medicine might be in a liquid form yet its salt is a solid. Sometimes you want to make a hydrophobic salt so that its stability is higher in high humidity. Sometimes you wish to improve the taste. There are plenty of factors.

Most likely the reason for a mixture of medicine and its sodium salt is its controlled release and some buffering action. In case of your carmicide which is a mixture of sodium citrate and citric acid, is a buffering system and secondly citric acid alone is very corrosive and very bad tasting (tart). Fucidin is only allowed as a Na-salt.

This review will tell you the principles behind choosing a salt.

Go to Google Scholar and read: Gupta et al. Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations, Molecules 2018, 23, 1719; doi:10.3390/molecules23071719

The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development.

API= active pharmaceutical ingredient

Answer 2

In addition to M. Farooq's answer, there is also the question of the chemical's stability and our body's metabolic route for it. For example, most tryptamines you will find in the fumarate salt form, and this is because most other salts and the free base forms of these chemicals deteriorate rapidly.

On the metabolic side of this answer, take Tianeptine as an example. Simply changing the salt form from Tianeptine sulfate to Tianeptine sodium is effectively changing the drug from an instant release to an extended release form. This is because our body metabolizes the two salts of the chemical differently, and so one requires a lower dose, has a faster onset and shorter duration, and the other requires a higher dose but takes longer to onset and lasts much longer. Hope this provides some insight to your question.