Speed Case Study

The Client

A large, US-based Pharmaceutical company with their own in-house development group used our Speed service at the end of last year. They had a licensed compound with an extensive but disjointed formulation development package from a small biopharmaceutical company. The previous formulation work had been carried out by five different service providers. This led to some very confused thinking.

The Problem

The client had an oral compound in Phase I testing which had already been through formal GLP tox testing. However, the insufficient exposure found in man was limiting higher dosing. All formulation approaches had apparently already been explored. The failure to improve exposure would have resulted in the killing of the compound.

How Speed Worked

The first action we took was to screen the different delivery options: Amorphous, Crystalline and Solubilized. We revisited and reexamined the problem with a much broader selection of excipients and employed alternative processing techniques. This enabled us to diagnose the root cause of the insolubility. We were able to supply the client with fresh Leads within 7 weeks of starting the service.

The Results

• Solubilized formulations eliminated due to high excipient to drug ratio
• Methodically established that even modified crystalline forms gave insufficient exposure
• Stabilized amorphous form identified as possible option
• Lead formulation composition (excipient type, stabilizers and ratio) identified after 1 iteration in vivo
• Scalable solvent free process identified and 10 kg of Material supplied for tox
• Repeated tox testing with the new form: no effect from excipients and increase of over 10 fold exposure achieved
• Our scientists worked with the client’s patent attorneys to draft Specific Formulation patent covering IP for client

The Speed service provided the client with a robust solution for the tox form with good exposure. This meant that the clinical exploration could recommence at higher levels.