Identification and Prevention of Particulates in a Parenteral Solution of a Protein Kinase B Inhibitor.

Abstract

The aim of this work was to identify the root cause of particulates in a parenteral solution formulation of a protein kinase B inhibitor (AKT inhibitor) and to devise a formulation fix. While standard potency/purity analyses did not reveal degradation, it was determined that the mass of the particulates corresponds to that of a "dimer-like" degradation product. The dimer-like molecule manifested itself as particulates rather than impurities in standard HPLC analysis. Particulate formation was found to be pH dependent. Consequently, an optimum formulation pH at which the compound has adequate solubility and the rate of particulate formation is slow was identified.