Plastics preservative loss

A sterile product incorporated a preservative system to cover withdrawal of a multidose liquid product. The product passed the USP XX microbial challenge test when first made and packed. After six months it was noticed that the level of ethylenediamine tetra acetate (EDTA) had significantly reduced, possibly by chelation with heavy metals + surface adsorption onto the plastic. A repeat microbial challenge test was not passed. It was theorised that this was due to slight preservative loss coupled to the loss of EDTA which tended to enhance the preservative efficacy, i.e. a chemical + physical change (preservative adsorption) had created a drop in preservative efficacy. Changing the EDTA/preservative levels was subsequently necessary in order to meet the microbial challenge test over the full shelf-life period. 

Problems associated with preservative loss with plastic materials are expounded under aseptic processes and preservative systems. 

The Extrelut cleanup method is suitable for most foodstuffs, such as cheese, yogurt, and other samples that tend to form emulsions during extraction. The prepacked or refilled Extrelut column in a plastic tube consists of a wide-pore kieselgel column. A sample is homogenized in 0.5 N sulfuric acid, diluted with water, and applied onto the Extrelut column for at least 15 min. The absorbed preservatives are eluted with a chloroform - isopropanol (9 1) mixture, and the elu-ate is collected and evaporated carefully nearly to dryness. The last few milliliters of solvent are removed with a gentle flow of nitrogen to prevent substantial losses of BA and SA, which have relatively high vapor pressures. The residue is transferred with methanol into a 10-ml volumetric flask and diluted to volume with methanol. To speed up the dissolution, the use of an ultrasonic bath is recommended. The filtered extract is analyzed on a /zBondaPak Cl8 column, with a... 

Adsorption Loss of metals due to adsorption to glass surface Loss of oily materials due to adsorption to plastic surface Use of plastic containers, preservation with nitric acid to pH < 2 Use of glass containers, preservation with sulfuric acid to pH < 2... 

Topical and Ophthalmic Preparations Appearance (clarity, color, and especially homogeneity), odor, pH, resuspendability, consistency, particle size, weight loss (of more importance if plastic containers are used). Sterility and preservative levels also must be considered if the product is intended for ophthalmic administration. 

Khat is purchased as bundles of dried and fresh leaves and buds. For transport purposes, it is usually wrapped in plastic bags or banana skins to preserve its moisture content - loss of activity is observed after 48 h if the plant material dries out. However, the drug can also be obtained as dried crushed leaves or in powdered form. These materials are either chewed or used to prepare an infusion which is drunk like tea. The major part of the pharmacological action is due to cathinone, which acts as a central nervous system (CNS) stimulant, promoting excitation, reducing the need to sleep and enhancing communication. 

Preservatives such as the methyl and propyl parabens present in formulations can be sorbed into mbber and plastic membranes and closures, thus leading to decreased levels of preservative and, in the extreme, loss of preservative activity. 

Chlorhexidine is also cationic like BKC and exhibits similar incompatibilities. It is not as stable as BKC to autoclaving and may irritate the eyes. It tends to be more favoured in Europe than in the United States, and is particularly used in contact lens products. Chlorobutanol and phenylethyl aclohol are also widely used in ophthalmic products. However, chlorobutanol will hydrolyse in solution, and autoclaving is not usually possible without loss of preservative activity. It is also volatile and may be lost through the walls of plastic containers. 

Finally, the possibility of product migration into the pack (e.g. loss of preservatives) coupled with permeation of oxygen, carbon dioxide and moisture must also be consid ered as a factor which could cause changes in the migratory nature of constituents in the plastic. 

Adsorption, where the preservative attaches itself to the surface of a plastic, tends to vary according to the type of plastic, constituents in the plastic, surface treatment, surface area of the plastic. Adsorption has been found with most mercurials, including Thiomersal, benzalkonium chloride and bromide, etc. Small amounts of chlorhexidine, benzoic acid and hydroxybenzoates have also had losses reported for certain plastics. 

The evaluation of inhalation solutions and solutions for inhalation should include appearance, color, assay, degradation products, pH, sterility, particulate matter, preservative and antioxidant content (if present), net contents (fill weight and volume), weight loss, and extractables or leachables from plastic, elastomeric, and other packaging components. 

The stability evaluation of nasal solutions and suspensions equipped with a metering pump should include appearance, color, clarity, assay, degradation products, preservative and antioxidant content, microbial limits, pH, particulate matter, unit spray medication content uniformity, number of actuations meeting unit spray content uniformity per container, droplet or particle size distribution, weight loss, pump delivery, microscopic evaluation (for suspensions), foreign particulate matter, and extractables and leachables from plastic and elastomeric components of the container, closure, and pump. 

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