Modeling of the solution interaction properties of plastic materials used in pharmaceutical product container systems.

Material/water equilibrium binding constants (Eb) were determined for 14 organic solutes and 17 plastic raw materials that could be used in pharmaceutical product container systems. Correlations between the measured binding constants and the organic solute's octanol/water and hexane/water partition coefficients were obtained. In general, while the materials examined exhibited a wide range of binding characteristics, the tested materials by and large fell within two broad classes: (1) those that were octanol-like in their binding characteristics, and (2) those that were hexane-like. Materials of the same class (e.g., polypropylenes) generally had binding models that were very similar. Rank ordering of the materials in terms of their magnitude of drug binding (least binding to most binding) was as follows: polypropylene < polyethylene < polyamide < styrene-ethylene-butylene-styrene < copolyester ether elastomer approximately equal to amine-terminated poly fatty acid amide polymer. The utilization of the developed models to estimate drug loss via sorption by the container is discussed.

Accumulation of organic compounds leached from plastic materials used in biopharmaceutical process containers.

Plastic materials are widely used in medical items, such as solution containers, transfusion sets, transfer tubing, and devices. An emerging trend in the biotechnology industry is the utilization of plastic containers to prepare, transport, and store an assortment of solutions including buffers, media, and in-process and finished product. The direct contact of such containers with the product at one or more points in its lifetime raises the possibility that container leachables may accumulate in the finished product. The interaction between several commercially available container materials and numerous model test solutions (representative of buffers and media used in biopharmaceutical applications) was investigated. This paper summarizes the identification of leachables associated with the container materials and documents the levels to which targeted leachables accumulate in the test solutions under defined storage conditions.

Performance characteristics of an ion chromatographic method for the quantitation of citrate and phosphate in pharmaceutical solutions.

The performance of an ion chromatographic method for measuring citrate and phosphate in pharmaceutical solutions is evaluated. Performance characteristics examined include accuracy, precision, specificity, response linearity, robustness, and the ability to meet system suitability criteria. In general, the method is found to be robust within reasonable deviations from its specified operating conditions. Analytical accuracy is typically 100 +/- 3%, and short-term precision is not more than 1.5% relative standard deviation. The instrument response is linear over a range of 50% to 150% of the standard preparation target concentrations (12 mg/L for phosphate and 20 mg/L for citrate), and the results obtained using a single-point standard versus a calibration curve are essentially equivalent. A small analytical bias is observed and ascribed to the relative purity of the differing salts, used as raw materials in tested finished products and as reference standards in the analytical method. The assay is specific in that no phosphate or citrate peaks are observed in a variety of method-related solutions and matrix blanks (with and without autoclaving). The assay with manual preparation of the eluents is sensitive to the composition of the eluent in the sense that the eluent must be effectively degassed and protected from CO(2) ingress during use. In order for the assay to perform effectively, extensive system equilibration and conditioning is required. However, a properly conditioned and equilibrated system can be used to test a number of samples via chromatographic runs that include many (> 50) injections.

Leaching of organic acids from irradiated EVA plastic as a function of solution pH and polarity.

The leaching of several target organic acids from an irradiated ethylene vinyl acetate material, such as those used as a solution product container, is examined as a function of solution pH and polarity. The targeted compounds included highly soluble weak acids such as acetic and formic acids, and larger, more lipophillic acids such as myristic, palmitic, and stearic acids. The leaching of these compounds was examined over a pH range of 3 to 11 and in various ethanol/water proportions. While pH and solution polarity had only a modest impact on the accumulation of the acetic and formic acids, the accumulation of the fatty acids was greatly affected by both factors. It is suggested that the accumulation of these leachables at high pH is influenced by two processes. The first process, partitioning, the speciation of the acidic leachables (protonated versus dissociated form) contributes to the pH trends observed. In this case, entities that already exist in the plastic partition themselves between the plastic and solution via migration. A second, more important, contributor to the leaching of these acids is a pH-dependent increase in their availability arising from an unspecified reactive process.