Velesco’s Non-Clinical Formulation Philosophy – Part 1

As I’ve gained more time in the CRO world versus big pharma, I have come to see that there are two fairly distinct schools of thought for determining pre-clinical formulations for very early stage compounds.  One uses the compound structure and an iterative process to determine an appropriate vehicle for early stage formulations.  The other uses a high throughput screening methodology to pinpoint a vehicle.

At Velesco, we firmly believe in a structural-based approach to non-clinical formulations and solubility screening.  Why?  We are chemists, and our years of experience in this field have given us the tools to be able to recognize clues in your molecule’s structure.  These clues can help steer us to a starting point for solubility screening.

I don’t want you to assume that we use a structural based approach just to exercise our chemistry minds.  There is a method to our madness.  We are keenly aware of the crucial importance of solvent order of addition and the energy required in a system to solubilize your compound.  These considerations may make or break a formulation’s success.

Order of Addition

We have performed solubility screening projects for clients who have had high throughput screening done that gives a false negative.  For example, a client’s compound was insoluble in screening.  However, we were curious as to why the compound didn’t solubilize in 50:50 DMSO:PEG 400 (Dimethylsulfoxide: Polyethylene Glycol 400) and wanted to repeat that vehicle.  We compared adding 50:50 DMSO:PEG 400 to the drug and sonicating with adding DMSO, sonicating, then adding PEG 400 and sonicating again.  The drug was fully soluble in this mixture up to the concentration required by the client.  Here, order of addition was the absolute key.  The client didn’t need us to formulate a fancy vehicle for their toxicology study; they just needed a different order of addition of common vehicle components.

Stay tuned for a further discussion of this topic.

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