Adsorption onto and Absorption into Containers and Transfer of Container Components into Pharmaceuticals

Pharmaceuticals may interact with packaging and containers, resulting in the loss of drug substances by adsorption onto and absorption into container components and the incorporation of container components into pharmaceuticals. Diazepam in intravenous fluid containers and administration sets exhibited a loss during storage due to adsorption onto glass and adsorption onto and absorption into plastics.740 741 Nitroglycerin, a liquid with a significant vapor pressure, is also significantly adsorbed onto and absorbed into containers. Decreases in the drug content of nitroglycerin tablets in SP742 and nitroglycerin solutions in glass and plastic containers743 744 due to adsorption/absorption were analyzed by a diffusion model and a model consisting of adsorption onto the surface followed by partitioning into the plastic.

Polyvinyl chloride (PVC), a polymer often used for pharmaceutical containers, is known to interact with various drug substances. Adsorption and absorption of nitroglycerin onto

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Figure 189. An attempted Arrhenius plot for the rate of absorption of nitroglycerin into a PVC container (pH 5.6). (Reproduced from Ref. 745 with permission.)

and into PVC conformed to apparent first-order kinetics, and the apparent rate constant describing uptake showed nonlinear Arrhenius behavior (Fig. 189).745 Absorption of clomethiazole edisylate and thiopental sodium into PVC infusion bags was observed.746 The pH dependence of adsorption/absorption of acidic drug substances such as warfarin and thiopental and basic drug substances such as chlorpromazine and diltiazem indicates that only the un-ionized form of the drug substance is adsorbed onto or absorbed into PVC infusion bags.747 The absorption was correlated to the octanol-water partition coefficients of the drugs, suggesting that prediction of absorption from partition data is possible.748 749 A parameter referred to as sorption number (S„ ) was used to predict drug loss to PVC bags.750 751 Sn is defined by the plastic-infusion solution partition coefficient of the drug, the diffusion coefficient of the drug in the plastic, the fraction of the drug un-ionized in solution, the volume of the infusion solution, and the surface area of the plastic. As shown in Fig. 190,

logPocunoi

Figure 190. A log-log plot of sorption number (S„ into a PVC container versus octanol-water partition coefficient (Poctanoi) for a number of drugs. Drugs were stored at 15-20°Cfor 1, (□) and 24 h (■). (Reproduced from Ref. 750 with permission.)

logPocunoi

Figure 190. A log-log plot of sorption number (S„ into a PVC container versus octanol-water partition coefficient (Poctanoi) for a number of drugs. Drugs were stored at 15-20°Cfor 1, (□) and 24 h (■). (Reproduced from Ref. 750 with permission.)

Figure 191. Accumulation of carboxylic acid alkyl ester from polypropylene container at 25°C and pH 2. -,

Predicted from diffusion and degradation rate equation; ---, diffusion-controlled accumulation; observed. (Reproduced from Ref. 748 with permission.)

Figure 191. Accumulation of carboxylic acid alkyl ester from polypropylene container at 25°C and pH 2. -,

Predicted from diffusion and degradation rate equation; ---, diffusion-controlled accumulation; observed. (Reproduced from Ref. 748 with permission.)

the logarithm of this parameter was correlated with the logarithm of the octanol-water partition coefficients of various solutes.

Polymers such as nylon 6 (polycaprolactam) are known to adsorb drug substances such as benzocaine.752 Glass surfaces are also known to adsorb drug substances. Chloroquine solutions in glass containers decreased in concentration owing to adsorption of the drug onto the glass.753

Rubber closures are also known to absorb materials, including drugs. Absorption of preservatives such as chlorocresol into the rubber closures of injectable formulations has been studied extensively.754-756 Water permeability of rubber closures used in injection vials is considered an important parameter in assessing the closures, but quantitative prediction of water permeability through rubber closures is difficult because the diffusion coefficient of water is dependent on relative humidity.757

In addition to absorption onto and absorption into containers, transfer of container components into pharmaceuticals may affect the perceived stability/quality of drug dosage forms. Adsorption of volatile components from rubber closures onto freeze-dried parenterals during both dosage form processing and storage brought about haze formation upon reconstitution.758-760 Leaching of dioctyl phthalate, a plasticizer used especially in PVC plastics, into intravenous solutions containing surfactants was observed.761 762 The time course of dissolution of an alkyl ester of a carboxylic acid, which originated in a polymer composite packaging material, from polypropylene containers was predicted by a diffusion rate and degradation rate equation, as shown in Fig. 191.763

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