Expert Interview : 5 questions to Sonia Lombardo

We asked 5 questions to Dr. Sonia Lombardo, Preformulation Solid State Engineer at SEQENS, about bioavailability improvement and pre-formulation studies during drug development.

1/ What is your background?

I am a pharmacist with a background in pre-formulation and formulation of oral dosage forms. I graduated from Paris Saclay University and then worked for three years on polymeric nanoformulation in Germany. I joined Seqens soon after in 2022 and integrated the Solid State department of the Seqen’s Lab, in Porcheville. I have been developing Seqens’ pre-formulation and formulation activities since then and I am dedicated to our SeqensUP! Offer.

2/ How crucial are pre-formulation studies for drug substance development at early-stage?

Most drug development failure are due to poor bioavailability of the API. To enable a “right-the-first-time” approach during your drug development, you need to gather and understand physicochemical properties of your molecule. It is the best way to de-risk development stages and make confident decisions about the most appropriate formulation system, to avoid failure later on.

3/ If an API has low bioavailability properties, what are the best strategies to improve it?

There are several strategies available. Depending on your API’s classification within the Developability Classification System (DSC), you can improve your compound properties through solid state modification and focus on the most appropriate formulation system (for example hot melt extrusion (HME), spray-drying, lipid-based systems or other potential formulations strategies).

4/ Typically, how long does it take to make a first formulation for preclinical assays?

Although it remains a case-to-case study, on average it will take 3 to 4 months. Preformulation studies need to be performed first to ensure API characterization and evaluate potential bioavailability challenges using the BCS/DCS classification, as well as excipients screening.

5/ How do you deal with an API exhibiting poor permeability, such as BCS/DCS class III drug?

One option would be to modify the API itself as a more lipophilic prodrug. If this is not possible, lipid-based formulations can be another option. There are several techniques available depending on its overall physicochemical properties, like its LogP, pKa and solubility in various excipients. Looking at efflux transporters can also explain the poor permeability of the API.