Parenteral Administration - Formulation

Parenteral Administration - Formulation

8. Parenteral Administration:

Parenteral administration by the intravenous route is preferred for seriously ill children and for clinically unstable term and preterm neonates (in developed country settings). Some parenteral preparations are administered by the subcutaneous and intramuscular routes. The limited muscle mass of newborns and, in particular of preterm infants, constrains the use of intramuscular injections. Other routes of administration, e.g. intraosseous, are used in emergency cases.

Most children have a fear of injection needles. Possible alternatives, especially suited for children undergoing frequent or long-duration treatment, such as needle-free injection devices (jet injectors), that drive small droplets through the skin by high pressure, could be considered, e.g. for subcutaneous
administration. However, experience of their use in paediatric populations, especially in smaller children is limited.

Repeated injections should be avoided for children unless they can be given intravenously via catheter or injection ports that can remain in place for the length of the treatment. Reducing the number of injections by formulation of sustained-release preparations requires consideration of increased blood perfusion in children, usually increasing absorption from tissue depots. The clinical need to limit fluid uptake, especially in very young children, must also be taken into account.

Age- and weight-related preparations (injection volume and strength) are preferred in order to provide an acceptable injection volume, and to avoid dosing errors due to improper use of multi dose preparations and errors in calculation of the dilution required to obtain measurable volumes. It is helpful to state on the label the size of syringe that permits accurate administration.

The size of the presentation should not allow significant over dosage if the dose or volume is miscalculated. In general the volume in the vial should be no greater than 10 times the smallest dose to be measured. 

8.1 Formulation:

Aqueous preparations (solutions or suspensions) must be adapted to the physiological conditions on the application site. The tolerances for deviations in pH and osmolality are dependent on the route of administration. In particular, subcutaneous administration is highly sensitive because dilution of the injected volume and its escape from the injection site proceed slowly. Hyperosmolar injections and injections with extreme pH may cause pain and irritate peripheral veins.

Formulations for neonatal patients are usually aqueous solutions intended for intravenous administration. Target volumes and electrolyte contents are important for all paediatric patients; however, these are critical for neonates (19).

It is crucial to consider the safety profile of each excipient and its suitability for the intended use (see section 4.3).

Attention should be paid to the potential adsorption of the API on to the surfaces of plastic containers and catheters, and to leaching of plasticizers from containers and catheters to the parenteral preparation.

Some APIs are presented as powders or lyophilisates to be reconstituted before administration. It is important that clear instructions on the reconstitution and information on storage conditions and duration appear on the label or product information.

Development of Paediatric Medicines: points to consider in formulation, 
(Annex 5, WHO Technical Report Series 970, 2012)

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