Pharmacology salts: HcL vs Citrate vs Sulfate

[LuvGlock]

I'm wondering what significance the salt attached to a drug has, if any. Why is there no Morphine Citrate (or is there?), why is Fentanyl Citrate not Fentanyl Sulfate?

Also, why is 38mg of Diphenydramine Citrate equivalent to 25mg of Diphenhydramine HCl?

Probably not knowledge necessary to be a medic, but what can I say? I'm a nerd.

If anyone can explain this to me like I'm 4, please do.

 

[silver]

"The main objective of a salt-selection study is to identify the salt form most suitable for development. The following four parameters are often considered primary or essential criteria for the selection of a particular form:

-Aqueous solubility measured at various pH values, depending upon the intended pharmaceutical profile
-High degree of crystallinity
-Low hygroscopicity (i.e., water absorption versus relative humidity), which gives consistent performance
-Optimal chemical and solid-state stability under accelerated conditions (i.e., minimal chemical degradation or solid-state changes when stored at 40 °C and 75% relative humidity)."

http://pharmtech.findpharma.com/pha...lopment/ArticleStandard/Article/detail/500407

 

[systemet]

I'm wondering what significance the salt attached to a drug has, if any. Why is there no Morphine Citrate (or is there?), why is Fentanyl Citrate not Fentanyl Sulfate?

There are other salts of morphine used clinically, including the morphine citrate you're suggesting.

The conjugate base, e.g. the citrate, sulphate, etc. affects the chemical properties in the pill or vial before it's introduced into the body. Once introduced, there's plenty of other bases for the morphine to interact with, so it becomes a bit of a non-issue.

Also, why is 38mg of Diphenydramine Citrate equivalent to 25mg of Diphenhydramine HCl?

This is fairly trivial -- it depends on the molar mass of the compounds. For diphenhydramine HCl, we're looking at a molar mass of 292 g/mol, and for diphenhydramine citrate, we're looking at a molar mass of 447 g/mol. This is because the citrate component has a higher molecular weight (192g/mol) compared to a chloride (35 g/mol). [I know these numbers don't quite add up, as I've rounded a little].

We can calculate how many molecules (i.e. how many moles, or "mol") of diphenhydramine we get by dividing the mass given by the molar weight. So 25mg of diphenhydramine HCl ends up giving us 850 umol (micromoles) of diphenhydramine and 850 umol of HCl. 38mg of diphenhydramine citrate gives us about 850 umol of diphenhydramine, and 850 umol of citrate.

So you have to give a larger mass of diphenhydramine citrate to get the same amount of diphenhydramine. This also explains the difference in dosing when using calcium chloride and calcium gluconate.

Probably not knowledge necessary to be a medic, but what can I say? I'm a nerd.

It's important to a point. It's definitely interesting. If you can understand how acids and bases work, it can help you realise why a drug with a highly substituted nitrogen, that's predominately ionised at physiologic pH isn't going to cross the blood brain barrier easily, e.g. succinylcholine.

It can also help explain exactly why people are mixing powder cocaine (cocaine HCl) with sodium bicarbonate to make freebase cocaine (i.e. crack), and how these two substances differ.

If anyone can explain this to me like I'm 4, please do.

If there's anything you didn't understand / want more detail on, let me know. I think there's a few people on the forum with chemistry degrees who can explain this better.

 

[LuvGlock]

No, that's about what I'm looking for. Thank you!

I love this forum more every day.