Characterization of Microbial Growth Potential in Antibody Drug IV Admixtures by Microbial Challenge.

Monoclonal antibody (mAb) drug products (DP) for IV administration are commonly diluted in a diluent such 0.9% sodium chloride (saline) or 5% dextrose (D5W) injection yielding IV admixtures before infusion or injection. During dose preparation, storage, and administration, the sterility of IV admixtures must be maintained to ensure patient safety.

Nuances in the Calculation of Amorphous Solubility Enhancement Ratio.

The theoretical amorphous solubility enhancement ratio (R) can be calculated based on the free energy difference between amorphous and crystalline forms (ΔG), using several experimentally determined input parameters. This work compares the various approaches for the calculation of R and explores the nuances associated with its calculation. The uncertainty of R values owing to experimental conditions (differential scanning calorimetry heating rates) used to measure the input parameters was determined for 3 drugs (indomethacin, itraconazole, and spironolactone).

Biorelevant Media Slows the Solution-Mediated Phase Transformation of Amorphous Spironolactone.

Solution-mediated phase transformation (SMPT) can reduce the high drug concentration expected from amorphous formulations, eliminating the improvement in drug absorption one hoped to gain from this high energy drug state. The differences in SMPT of a supersaturating system were compared in biorelevant media (fasted state simulated intestinal fluid and fed state simulated intestinal fluid) and United States Pharmacopeia compendial medium, simulated intestinal fluid without pancreatin. Amorphous spironolactone underwent SMPT to the same hydrate of spironolactone in all 3 media which was confirmed by the decrease in dissolution rates assessed in a flow-through dissolution apparatus, as well as by the appearance of crystals on the amorphous solid surface detected by polarized light microscopy.

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs.

Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closed-form analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters.