Multidose containers

Atypical parenteral o/w emulsion is composed of lipid droplets (10-20%), emulsiLer, and osmotic agent it is administered by either intravenous (IV) bolus or IV infusion. In addition, when an emulsion formulation is packed in a multidose container, antimicrobial agents should be included in the formulation to prevent the growth of microorganisms. 

The system then selects additives, depending on the specification required (e.g., an antimicrobial will only be added if a multidose container is specified or a tonicity adjuster will only be added if the solution is hypotonic). The selection strategy is generally on the basis of ranking with some specific rules. 

Utilization Period The period of time during which a reconstituted preparation or the finished dosage form in an opened multidose container can be used. 

Oral solutions, emulsions and suspensions are defined as being supplied in single-dose or multidose containers. Each dose from a multidose container is administered by means of a device suitable for measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL or multiples thereof or an oral syringe for other volumes. 

Water supports the growth of micro-organisms, therefore oral aqueous solutions, suspensions, emulsions and solubilisates in multidose containers should be preserved. Preservatives may be used for that purpose as well as excipients with preservative properties, such as propylene glycol. See Sect. 23.8 for extensive information on preservatives. Table 5.18 summarises preservatives with properties especially relevant for oral liquids. 

Most ready-to-use liquid preparations for nebuUsatimi are supplied in single-dose vials and according to the European Pharmacopoeia, they have to be sterile and preservative-free. When they are supplied in multidose containers, they have to be sterile if they do not contain an antimicrobial preservative or when the preparation does not have adequate antimicrobial properties itself. The multidose containers have to be designed to prevent microbial contamination of their contents during storage and use. A wide variety of preservatives is available but some of them, like phenol, bisulfites, edetate and benzalkonium chloride can cause airway irritation and result in bronchoconstriction or reduce the efficacy of the medicine [57]. Other compounds such as chlorobutanol, methyl- and propyl-parahydroxybenzoate and also benzalkonium chloride are cUiotoxic at... 

Aqueous nasal drops and nasal sprays are preserved when they are supplied in multidose containers. In order to get a low level of microbiological contamination at the start, the use of sterilised water or sterilised solutions of preservatives as primary materials is recommended. 

Unless otherwise justified, aqueous ear preparations supplied in multidose containers contain a suitable antimicrobial preservative at a suitable concentration, except where the preparation itself has adequate antimicrobial properties. An example of this is Bacicoline B . These ear drops contain a borate buffer, but no preservative. This was accepted by the licensing authorities because borate buffers have some antimicrobial properties and because the beyond-use date is 10 days after opening. 

Ear drops that may, or should reach the middle ear are sterile aqueous solutions, with a preservative added when they are supplied in multidose containers. The monograph Ear Preparations of the Ph. Eur. states that ear drops that may or should reach the middle ear, should be sterile and free from antimicrobial preservatives. That sterility is required seems clear, as the solvent in ear drops intended for the middle ear is water, and the middle ear has little defence because of its low blood flow. When preservatives are not to be used, such ear drops should be supplied in single-dose containers, unless otherwise justified. 

According to the Ph. Eur. ear drops are usually supplied in multidose containers of glass or suitable plastic material that are fitted with an integral dropper, or with a screw cap of suitable materials incorporating a dropper and a rubber or plastic teat. Alternatively, such a cap is supplied separately. 

If a preservative is required for multidose containers, sterile and preserved vehicles can be used (see Table 10.10). The same considerations regarding the use of preservatives in eye drops apply to eye lotions. 

For multidose containers - the period after opening after which the contents must be used or discarded this period should not exceed 4 weeks... 

According to national legislation the label mentions the dosage form (eye cream or eye ointment), the route of administration (ocular use), the intended use, the storage conditions, the expiry date and, for multidose containers, the beyond-use date after which the opened preparation must not be used. This period should not exceed 4 weeks. If necessary the label also bears warnings and mentions that the contents should be brought to room temperature before administration if the tube is stored in the refrigerator. 

Multidose containers and the environment were found to be the source of a number of nosocomial viral infections [25-33]. 

Maximum usage periods for patients after opening the package, for medicines in multidose containers, with a standardised formula, are given in Table 22.15. These maximum usage periods are only valid within the shelf life of the preparation. 

Fig. 22.3 Flow chart for the assignation of usage periods of dosage forms in multidose containers...

In this section the general requirements for eye drop containers is discussed. Various multidose containers and some single use containers are described. 

Be reliably reclosable in case of multidose containers, or in case of single-dose packaging, the closure cannot be reclosed... 

Eye drops are mostly dispensed in a multidose container. The Ph. Eur. describes that this container should contain a maximum of 10 mL [28]. 

A strip is defined as a multidose container consisting of two layers, usually provided with perforations, suited for containing single doses of solid or semisolid preparations [26]. 

Fruit and berry juices are widely used as flavor bases for soft drinks, and most of these are concentrated by the removal of water under vacuum to give a commercial product, which is between four and six times stronger than the original juice. The flavor value of these concentrates depends not only on the degree of concentration but on the precise processing conditions used in their manufacture. From an application point of view, fruit products may be offered in sealed containers that have been pasteurized, in which case the whole contents must be used once the container has been opened, or they may be in multidose containers the contents of which contain a permitted preservative, usually sodium benzoate. All fruit-based flavorings are best stored under refrigeration or in a cold store. Fruit essences also may be... 

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