Question

Formulation considration of parenterals

Answer 1

The parenteral preparations are intended to be administrated through the human or animal body, either by direct injections (for example, bolus intravenous (IV), intramuscular(IM) or subcutaneous (SC)) or by infusion with a controlled infusion rate or by direct implantation through IM or SC.

They must meet the following minimum compendia criteria(1, 2,3):

•    To be sterile and pyrogen-free
•    To be clear or practically exempt of visible particle and to be free from sub-visible particles as required by pharmacopeias EP, USP and JP
•    No evidence of phase separation for the emulsions, or aggregates formation for aqueous dispersion such injectable Mab (monoclonal antibody) preparations
•    In case of suspensions, the use of appropriate particle size and any sediment should be readily dispersed upon shaking to give stable formulations and ensure the correct dose to be withdrawn and injected.

Parenteral preparations may require the use of excipients that should be biocompatible, be selected for the appropriate use and to be included at the minimum efficient concentration(3). The functionality of these excipients is as follows:

•    To make the preparations isotonic with respectto blood (glucose/dextrose, mannitol, sodium chloride…)
•    To adjust the pH to the physiological one (mineral or organic acids or salts)
•    To prevent the degradation of the drug substances (stabilizer…)
•    To ensure or increase the drug substance’s solubility
•    To provide adequate antimicrobial preservative property (only applicable to multidose preparations)

It should be stressed that excipients should not adversely affect the intended medicinal action of the drug products, nor at the concentration used to cause toxicity or undue local irritation.