Reformulation of a new vancomycin analog: An example of the importance of buffer species and strength

The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer’s instructions. In a separate vial, the Van-An formulation’s existing phosphate buffer species was supplemented with acetate buffer, which has a pKa in the desired range: between the pH values of the formulation (pH 3.9) and blood (pH 7.4). The formulations were injected using the dynamic injection apparatus into a flowing stream of isotonic Sorensen’s phosphate buffer at rates of 0.25, 0.5, 1, and 2 mL/min. The peaks obtained with the spectrophotometer were reproducible for each injection rate/formulation combination. For the phosphate-buffered formulation, the least amount of precipitation was obtained at the 0.25 mL/min injection rate. Acetate buffer was able to substantially reduce such precipitation, even at the highest injection rate. The opacity peaks for the formulation with the acetate addition were significantly smaller (P<.05) than those obtained for the unaltered formulation at all 4 injection rates. The results suggest that acetate is a better buffer species than phosphate for the pH range defined. Furthermore, we present evidence to support a generally applicable approach to screening new formulations of drug products that may be clinically useful for reducing the incidence of phlebitis in humans

Optimal Media for Use in Air Sampling To Detect Cultivable Bacteria and Fungi in the Pharmacy

Current guidelines for air sampling for bacteria and fungi in compounding pharmacies require the use of a medium for each type of organism. U.S. Pharmacopeia (USP) chapter <797> (http://www.pbm.va.gov/linksotherresources/docs/USP797PharmaceuticalCompoundingSterileCompounding.pdf) calls for tryptic soy agar with polysorbate and lecithin (TSApl) for bacteria and malt extract agar (MEA) for fungi. In contrast, the Controlled Environment Testing Association (CETA), the professional organization for individuals who certify hoods and clean rooms, states in its 2012 certification application guide (http://www.cetainternational.org/reference/CAG-009v3.pdf?sid=1267) that a single-plate method is acceptable, implying that it is not always necessary to use an additional medium specifically for fungi. In this study, we reviewed 5.5 years of data from our laboratory to determine the utility of TSApl versus yeast malt extract agar (YMEA) for the isolation of fungi. Our findings, from 2,073 air samples obtained from compounding pharmacies, demonstrated that the YMEA yielded >2.5 times more fungal isolates than TSApl