To develop an oral formulation for
PG301029, a novel potent agent for the treatment of Hepatitis C virus
infection, that not only has very low aqueous solubility but also degrades rapidly in water. The solubility of
PG301029 was determined in water, various aqueous media, and several neat organic
solvents. The stability of
PG301029 was monitored at room temperature in
buffers for 4 days, and in several neat organic
solvents for up to 8 mo.
Drug concentrations were measured by high-performance liquid chromatography (HPLC). Based on solubility and stability data,
Gelucire 44/14 and DMA (
N,N-dimethylacetamide) at a weight ratio of 2 to 1 were chosen as the formulation vehicle. After the vehicle was prepared, it was maintained in liquid form at approximately 40 degrees C until the
PG301029 was dissolved. The final formulation product was a semisolid at room temperature. The bioavailability of the formulation was tested on 4 female BALB/c mice.
PG301029 is insoluble in all tested aqueous media, while its solubility is promising in DMA. This compound is unstable in aqueous media and some organic
solvents; however, it is stable in DMA. This proposed formulation is able to hold up to 10 mg/mL of
drug and is stable at 4 degrees C. The shelf life for this formulation stored at 4degreesC is extrapolated to be greater than 4 years. This formulation dramatically increases the bioavailability of
PG301029. This nonaqueous formulation solves the stability, solubility, and bioavailability problems for
PG301029. This semisolid formulation can easily be incorporated into soft elastic capsules.