UpperNose™

The poor water solubility of an API can be characterised by either of the following mechanisms:

• Dissolution rate limited, where the surface area to particle volume is too high.
• Solubility rate limited, where the API is in a stable state (e.g. in a crystalline form).

When poor water solubility is limited by its dissolution rate, simple particle size reduction resulting in an increased surface area is likely to improve its solubility and in many this is sufficient to achieved the required exposure. This particle size reduction is readily accomplished by micronisation which is a well established and easy to access manufacturing operation.

For APIs limited by their solubility rate, then a more comprehensive process of identifying the most appropriate formulation strategy will be necessary.

UpperSolv™ can signpost the way with the following protocol:

1. Solubility screen where the API is dissolved with a range of solvents, co-solvents and solubilising excipients.
2. Applying enabling technologies to produce formulated intermediates and /or prototype product that have improved solubility. These include lipid based formulations (e.g. the API solubilised in a lipid based carrier is filled into capsules), amorphous formulations created by co-milling, amorphous Solid Dispersions created by spray drying.
3. Comparative in vitro characterisation and testing of the prototype enabled formulation followed by stability testing.
4. Comparative pharmacokinetic assessment (PK study) in small animal models.