DMF section 3.2.S.1 - General information

In the previous video, we have shown that the DMF in a CTD format consists of 7 sections. In this video we will talk about the first one, section 3.2.S.1.
This is a very simple section of the DMF, because it's usually informative and does not present many issues in terms of compliance with regulations.
If you are evaluating this section, the assessment is simple and straightforward, especially if the API is described in a pharmacopoeia. In this case, the information can be compared with the API pharmacopoeial monograph.

This section starts with the nomenclature. Here we will see different relevant names that can help us identify the API: the chemical name, compendial name, international non proprietary name, CAS number.
It's important to pay attention to APIs in salt form, because the CAS number can be different from one salt to the other, as shown in this example for the different codeine salts. It will also be different for the salt form when compared to the free base API, so the CAS number helps us identify exactly the form of the API that the DMF is about.
Here we may also find the product code, which identifies that API within the company, and can be different for different qualities of that API, for example different polymorphic forms, routes of synthesis, destination market, and so forth.

After that, we will look at the chemical structure - the structural formula including stereochemical configuration.
For example, if an API is chiral it must be clear through the structure if it's a racemic mixture or a specific stereoisomer. In the case of citalopram, this is a racemic mixture of two enantiomers, while escitalopram consists of only one enantiomer.
Here we will also see the molecular formula and the relative molecular mass.

And finally, this section also reports some properties of the API that may be relevant, especially those impacting the efficacy and safety of the drug product, for example
• Solubility in water and different solvents
• pKa
• Polymorphism
• Isomerism
• Partition coefficient (logP) which is related to permeability
• Particle size
• Hygrocospicity

It's important to keep in mind that this list is not exhaustive, and that it's not mandatory to present all these properties in this DMF section. The API manufacturer will decide which ones are considered relevant, based on his knowledge about the molecule.
For example, for a liquid API, hygrocospicity will not be relevant, since this is a property that describes the capacity of solids to absorb humidity.
On the other side, the pKa will only be applicable to ionizable APIs - although it's quite rare that an API is non-ionizable, considering that heteroatoms are usually present since they give pharmacological properties to molecules, and these are usually associated with their ionization. So it's important to evaluate the structure of the molecule and each specific case to conclude which properites will be relevant, and which ones may have their absence justified.

This was section 3.2.S.1 - in the next video we will talk about section 3.2.S.2 - the section that describes the manufacturer and the manufacturing process. Stay tuned!

Music: https://www.bensound.com