Oral formulation of a novel antiviral agent, PG301029, in a mixture of Gelucire 44/14 and DMA (2∶1, wt/wt)

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 buffess 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 ∼40°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°C. The shelf life for this formulation stored at 4°C 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

Total War and Limited Government: the German Catholic Debate at the Dawn of the Nuclear Age

The chapter recovers the debate among German Catholics over North Atlantic Treaty Organization (NATO’s) introduction of tactical nuclear weapons into the new West German army (Bundeswehr). Young Catholic scholars Ernst-Wolfgang Böckenförde and Robert Spaemann forcefully opposed nuclear weaponry in debate with German theologian Gustav Gundlach. The arguments turned chiefly on natural law and papal authority, less so on theology. The chapter reconstructs the argument and recasts it in terms of political theology, a category that seems well suited for thinking about an issue of such gravity and finality (nuclear apocalypse being the ultimate Schmittian exception) and which the authors knew but avoided because of its discrediting under Nazism. The birth of a critical political theology in the 1960s enabled thinking about creation and divine sovereignty that could argue the case and exploit Catholicism’s global standing without lapsing into pre-critical biblical interpretation and philosophical methods ill-equipped to think about nuclear war