CASE STUDY 2:
Salt Form Optimization and Lyophilized Parenteral Formulation Development
Client Profile
A Northeastern, privately held, emerging pharmaceutical company with less than 50 employees was focused in two therapeutic areas. They had recently obtained a large second round of financing. The client had an experienced management team and discovery scientists, and outsourced all of its preclinical development work.
Business Needs
The company had already nominated their candidate drug and had to get it into the clinic within 12 months.
Technical Challenges
The nominated candidate was a small molecule that had been synthesized as a mesylate salt. Due to overall scheduling pressures, the client decided to use the mesylate salt for early toxicology studies, but explore salt optimization in parallel to improve physicochemical characteristics.
A parenteral formulation of the mesylate salt was needed within three months, and the optimized salt formulation was required within six months. Initially, only 50 mg of API was available and the purity was sub-optimal, but gram quantities of higher purity material would be available within six weeks that could be used in the salt optimization process.
WLI Services
WLI quickly developed and qualified a stability-indicating HPLC method using the available material. We then implemented two parallel project tracks:
WLI determined the solubility of the drug in various vehicles to support a parenteral product, then developed parenteral formulations to support early non-GLP toxicology studies.
WLI prepared nine different salts and determined their solubilities in various vehicles, then identified the optimized salt for development and use in GLP toxicology studies and in the clinic. During this work WLI determined that the drug did not have sufficient liquid stability, so we developed three lyophilized formulations, and placed them on accelerated stability. From the resulting data, we selected the final formulation and optimized the compounding procedure.
Results
The client's short and long term needs were met on a timely basis. WLI assisted in technology transfer to the GMP manufacturing and stability facility within six months, supporting the overall project timeline to get to the clinic.
