Injectable products multidose

Preservatives should not usually be included in parenteral formulations except where a multidose product is being developed. The Committee for Proprietary Medicinal Products (CPMP) Notes for Guidance on Inclusion of Antioxidants and Antimicrobial Preservatives in Medicinal Products states that the physical and chemical compatibility of the preservative (or antioxidant) with the other constituents of the formulation, the container and closure must be demonstrated during the development process. The minimum concentration of preservative should be used, which gives the required level of efficacy, as tested using pharmacopoeial methods. Certain preservatives should be avoided under certain circumstances, and preservatives should be avoided entirely for some specialised routes. The guidelines also require that both the concentration and efficacy of the preservative are monitored over the shelf life of the product. In multidose injectable products, the efficacy of the preservative must be established under simulated in-use conditions. Table 9.2 shows some of the most commonly encountered preservatives in licensed products and their typical concentrations. 

The following is a suggested programme for the evaluation of a plastic container for a liquid multidose injection product (not lyophilised). 

Preservatives may inelude disinfeetant and antiseptic chemicals together with eertain compounds used almost exclusively as preservatives. They are added to mar industrial, including pharmaceutical, products which may, by their nature, support the growth of bacteria and moulds causing spoilage of the product and possibly infection of the user. In the field of pharmaceutical preservation, addition of an inhibitory substance to a multidose injection (Chapter 21) or the prevention of growth in aqueous suspensions ofdmgs intended for oral administration (Chapter 18) are prime examples. 

Most injections are formulated as aqueous solutions, with Water for Injections BP as the vehicle. The formulation of injections depends upon several factors, namely the aqueous solubility of the active ingredient, the dose to be employed, thermal stability of the solution, the route of injection and whether the product is to be prepared as a multidose one (i.e. with a dose or doses removed on different occasions) or in a singledose form (as the term suggests, only one dose is contained in the injection). Nowadays, most injections are prepared as single-dose forms and this is mandatory for certain routes, e.g. spinal injections such as the intrathecal route and large-volume intravenous infusions (section 2.2). Multidose injections may require the inclusion of a suitable... 

Aqueous products that are at greatest risk from microbial spoilage include solutions, suspensions, and emulsions for repeated oral, parenteral, or external use and include critical products such as multidose injections and eye drops. Unpreserved products without adequate antimicrobial efficacy should not be presented in containers intended for use on more than one occasion unless justified. When antimicrobial preservatives are used, their efficacy has to be demonstrated using the Ph Eur test for antimicrobial preservative efficacy. Factors to be taken into account in designing a preserved product include the nature of the preservative, its concentration in the product, the... 

The length or duration of time that the drug product will be used once the multidose injection is opened. 

For multidose sterile products, the preservative must be capable of reestablishing sterility between each use, whereas for a non-sterile topical cosmetic the function of the preservative might simply be to prevent growth. The associated toxicity of preservatives often limits the concentrations at which they can be employed thus, lower concentrations are generally employed for opthal-mic products and injectables. In choosing a preservative the likely capacity required, the rate of killing desired, and the ingredients and pH of the formulation must be borne in mind. 

Parenteral preparations are filled into various types of containers, depending on the nature of the product. Single-dose injections are filled into glass ampoules sealed by fusion or ex tempore into plastic syringes. Multidose injections are delivered in glass vials sealed with rubber closures with mechanical properties suitable for multiple piercing. Concentrates and powders for injections or infusions are also... 

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