What is a salt?

The majority of drugs (around 60%) are formulated as a salt. This says salts are important! But why? And what are they exactly? Here, PharmaDrama aka Prof. Simon Gaisford discusses the basic definition of a salt, how they are formed and why they are so popular in the pharmaceutical field.

See the video and read the transcript below:

Welcome to Pharma Drama, the channel where we look at the science of healthcare and healthcare products. In this video I’m going to talk about salts – what they are and why so many drugs are formulated as salts. There are some additional videos where I talk in more detail about salt chemistry, but here I’m just focussing on the basic definition. So, if that sounds good to you, get yourself a drink – ohh, coffee – and let’s make a start.

If I asked you what salt was, you’d probably tell me it’s the stuff you sprinkle on your chips to make them taste better. And you’d be right! Table salt is indeed a salt. Its chemical formula is NaCl and it comprises sodium ions (positively charged) and chloride ions (negatively charged) bound to each other. It’s a great example of a salt, but there are many others! It just happens that sodium chloride is universally known as salt.

You might guess, therefore, that a salt is defined as two ionic species bound together to form an electrically neutral compound. The positively charged ion is called a cation and the negatively charged ion is called an anion. In the case of sodium chloride the sodium ion has a single positive charge (and so is the cation) and the chloride ion has a single negative charge (and so is the anion), and when bound together they form a species, sodium chloride, that is electrically neutral. Salts do not always contain ions in equal ratios however. Calcium chloride has the formula CaCl2 because the calcium ion has two positive charges and so needs two chloride ions to form an electrically neutral species. You might also notice that both example salts I have given so far contain only inorganic ions (these types of salts are generally referred to as minerals), but we can of course have salts containing organic compounds and these are much more important to pharmaceuticals, because most drugs are organic compounds.

To make a salt of an organic compound we usually react an acid with a base (if you are unsure of acid and base chemistry there are videos on that, the links for which are below). When an acid reacts with a base, we form a salt plus water. When a strong acid reacts with a strong base (such as hydrochloric acid reacting with sodium hydroxide) the reaction proceeds almost to completion and we say the compounds have neutralised, in this case forming sodium chloride and water. More commonly though, a drug will be a weak acid or base. By reacting our drug with a strong base or acid (as appropriate) we make sure that nearly all the drug is converted to a salt. For instance, if we react ibuprofen (which is a weak acid) with sodium hydroxide (a strong base) we will generate ibuprofen sodium and water. In general, the two most common salt-formers used for drugs are sodium hydroxide (to form sodium salts of weakly acidic drugs) and hydrochloric acid (to form hydrochloride salts of weakly basic drugs), although a wide range of other salt formers can be used.

The majority of drugs (around 60%) are formulated as salts and you can tell if you are taking a salt by looking at the name of the drug on the packet; a salt form will have the drug name plus the counterion. Here, for instance, I have sodium ibuprofen. But why are so many drugs formulated as salts? There must be a good reason as the pharma industry wouldn’t go to all that trouble otherwise.

The answer lies in the fact that salts are comprised of ions bound together. When added to water the salt will dissociate – or split apart – releasing the ions. Because the ions have electrical charge, and water is a polar solvent, ions tend to be much more soluble in water than uncharged species. So that often helps increase the solubility of poorly water soluble drugs. Moreover, when a salt dissociates it may release either a proton or a hydroxide ion; Where a salt releases a proton it is called an acidic salt and where it releases a hydroxide ion it is called an alkali salt. This is important because protons and hydroxide ions will change the pH of a solution, and the solubility of acids and bases will change with pH. In fact, it is the change in pH upon dissolution of a pharmaceutical salt that is often the biggest factor in the increase in solubility, but don’t worry about why that is right now. I’ll discuss that in a separate video. And I should also note that where a salt dissociates but doesn’t generate either protons or hydroxide ions we call it a neutral salt. The table salt, sodium chloride, I mentioned at the start is a good example. Sometimes neutral salts are called electrolytes and you might have heard of that term, particularly in relation to sports drinks. An electrolyte drink is really just water containing a number of dissolved salts! They are particularly suited to athletes because strenuous exercise often causes loss of salt through sweating, but the body needs lots of ions to function properly!

One final thing to note is that dissociation is also usually rapid, so a salt form of a drug will dissolve faster than the corresponding free acid or base. This is why in some cases the salt form of a drug is used in fast-acting products. Again, using my old friend ibuprofen, you can see that the salt form is used in Nurofen express while the free acid is used in the standard tablet.

So there we are. A salt is a compound containing electrically charged ions bound together to create an electrically neutral species. They can be inorganic (minerals) or, more commonly for pharmaceuticals, organic. To make a salt of a drug, the drug itself must be a weak acid or base, but since most of them are salt formation is very common. The reason is because salts dissociate readily in water, often changing pH and creating ions that are water soluble. I’ll discuss more details of salt chemistry, and in particular the effect of changing pH, in another video but for now I hope you found that useful – if you did please hit the like button and consider subscribing as it really helps the channel. Otherwise, thank you so much for watching and I’ll see you again soon

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