Plastic containers, parenteral drug

One of the major drawbacks to the use of plastics is their heat intolerance. Because many plastics will melt or degrade at high temperatures, they are not well-suited to sterile applications. Parenteral drugs in particular require guaranteed sterility, and often this sterility can best be provided by glass containers. 

For drug preparations that will be used for internal or mucous membrane administration (i.e., parenteral preparations, ophthalmics, creams and salves, etc.), additional testing must be performed to assure that any leachants will not cause biological reactions that may be detrimental to the patient. To do this, a test protocol has been established that screens materials used in containers to test for biological interactions. This protocol should be applied to any plastic container closure systems regardless of the type of container that will directly contact pharmacopeial preparations in storage before they are invasively used. This includes all closure systems for parenteral vials. ... 

Plastic containers are also widely used for packaging parenteral products, such as intravenous (IV) infusion fluid containers, irrigation fluid containers, prefilled disposable syringes, and some administration sets. Polymeric containers have an added advantage of low breakage and are preferred when the SVP product is a highly toxic material such as oncolytic drugs. Typical polymeric... 

One of the important requirements of any packaging material is that it should not release any component into the drug product. Preparation of containers free of any leachables such as monomeric component is especially important for the containers of ophthalmics, parenteral products, and any liquid products. It was shown that di(2-ethylhexyl) phthalate was released from the PVC bags and that caused haziness of the taxol solution (37), USP/NF offers the protocol of chemical, spectral, and water vapor permeation tests and tolerances for plastic containers (55). Among those, chemical test is designed to give a quantitative assessment of the extractable materials in both organic solvents and water. 

Due to the need to check for particles, fibers, and possible discoloration in drug solutions transparent and colorless packaging materials are desirable. Hence, uncolored glass and plastic, bottles and bags, are commonly used as primary packaging for parenteral. To attain photo protection without losing VIS controllability, transparent containers or covers are necessary. 

The use of cosolvents in small-volume parenteral preparations is often critical due to the limited volume of solution that can be administered by a single injection. Thus, the required dose of drug must often be incorporated in 1 or 2mL of solution. Table 6 lists parenteral products containing cosolvents. The cosolvents most often used include ethanol, propylene glycol, glycerin, PEG 400, and, sometimes, dimethylacetamide. Other cosolvents, such as DMSO, have been used as solvents for parenteral formulations of experimental anticancer agents however, their use is restricted due to toxicity and potential incompatibilities with plastic administration devices. ... 

In busy hospital wards, the nursing staff often removes the outer cartons from parenteral products, and the preparations are stored without any protection against optical irradiation. In addition, ex tempore preparations are produced in the hospital pharmacy without outer protection and not usually protected when distributed to the wards (e.g., by use of aluminum foil) unless specifically instructed. According to the European Pharmacopoeia (2002), containers for parenteral preparations are to be made when possible from materials (usually glass or plastic materials) that are sufficiently transparent to permit visual inspection of the contents. As a consequence, the containers will offer no protection, or in some cases only limited protection, against photochemical decomposition of the drug substance or the formulation. 

Development of parenteral formulations of all-fram-retinoic acid is possible by using 2-hydroxypropyl-P-cyclodextrin, and inclusion into the carrier also leads to an improved photostability of the drug (Lin et al 2000). Aqueous cyclodextrin solutions are shown to extract plastic additives when stored in containers of polypropylene (Peiris et al., 1999 see Section 14.3). The result may be photosensitized decomposition of the drug. Photochemical stability of drug-cyclodextrin inclusion complexes are further discussed in Chapter 16. 

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