Velesco’s Non-Clinical Formulation Philosophy – Part 2

Apologies for the long delay between part 1 and 2 of this topic.  I’m sure that everyone was waiting with bated breath!

Last time, I wrote about the importance of order of addition to the successful solubilization of drugs.  This time, I will touch on energy and some notes that early drug developers need to know about solid state chemistry and solubility.

There are many great resources that describe solubility, so I won’t go deep into a technical lesson.

Here is an extremely technical paper that I particularly like.

http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/s200600.pdf

Here is a resource that explains solubility in more basic terms.

http://www.solubilityofthings.com/water

 

Terms:

Solute= the thing you want to dissolve, typically your drug substance

Solvent = the liquid you want to dissolve into

 

Energy

Since solubilizing a compound means that you are breaking it’s interactions with itself in the crystal state and trying to entice it to interact with a solvent, you can imagine why it takes energy to do this.  Some solubility challenges stem from the lack of preference of the drug for solvent.  However, some challenges arise from the need for a lot of energy to break the drug’s intermolecular associations.

 

How can you add this energy to the system?

One way is sonication.  Sonication is a fascinating topic, one that I would love to learn about further.  In essence, high frequency sound energy is used to dissolve solutes using sonic cavitation.  Cavitation produces bubbles in a liquid which collapse with a great amount of energy and heat.  These forces help break the drug-drug interactions.

Fun fact: Sonication is also used to clean jewelry!

 

Another way to add energy is just plain heat

Some molecules form extremely tight, layered intermolecular bonds.  Think diamonds.  The solubility challenges with these types of compounds can arise not from actual solubility, but from the inability to break apart the intermolecular bonds.  Sometimes sonication does not input enough energy to break these molecules apart.  However, if the molecule is chemically stable to high temperature, harsh conditions (70°C) for short periods of time can be used to disrupt the crystalline structure and allow the compound to go into solution.

 

Next time

Polymorphs – solvation includes breaking the crystalline lattice structure of the molecule..what happens when 2 lots of drug substance have different crystal structures?

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