CASE STUDY 2:
Development of a Parenteral Formulation of a Cytotoxic Natural Product
A virtual biopharmaceutical company had licensed a small molecule natural product from an academic institution.
The cytotoxic compound demonstrated anticancer activity and the company needed physicochemical profiling and parenteral formulation development to support their upcoming clinical program.
The company wanted either an aqueous or non-aqueous liquid formulation. However, the compound was known to isomerize in solution, so the company recognized that a lyophilized formulation might be required to achieve long-term stability. The anticipated human dose was 70-420 µg, to be delivered either by bolus or infusion injection.
The company needed a stable formulation developed which, upon dilution, would be stable for at least 12 hours, and preferably for 24 hours.
Wolfe Laboratories characterized the solubility properties of the anticancer compound, and used that information to inform formulation development.
The solubility of the compound was determined as a function of pH and in a series of excipients that are generally regarded as safe for intravenous dosing and are found in the harmonized monographs of the European and United States pharmacopoeias.
An administration vehicle was developed that provided sufficient stability and solubility for intravenous dosing. The vehicle also supported administration via intravenous infusion, and the compound remained stable in solution over a period of 48 hours at ambient temperature.
However, the compound did not have sufficient long-term stability, and so Wolfe Laboratories developed two lyophilized formulations. The lyophilized formulations maintained acceptable stability over 12 months of testing when stored under refrigerated conditions at 2 – 8 °C.
The product is currently being evaluated in Phase III testing, and at the time of this writing, had just been acquired by a large pharmaceutical company to boost their oncology franchise.