Variables Affecting Reconstitution Time of Dry Powder for Injection

A number of drugs are unstable in an aqueous environment, even when exposed for a short duration, thus requiring packaging, storage, and shipping in a powder or lyophilized state to keep the product stable during its shelf life. Used for parenteral administration, these drugs are commonly known as powder for injection (PI), powder for reconstitution, dry powder injection, or powder for constitution. USP 29–NF 24 describes more than 100 drugs available as dry powder for injection (1).

Typically, PI drugs are supplied in glass vials with rubber plugs and are mixed or reconstituted with a diluent (usually 5% dextrose solution, normal saline, bacteriostatic water, or sterile water for injection) before administration. An incompletely dissolved product can be hazardous to the patient, thereby making reconstitution a critical performance parameter for these products (1). USP defines the completeness of the reconstitution procedure as the state in which the solid dissolves completely; leaving no visible residue as undissolved matter or the constituted solution is not significantly less clear than an equal volume of the diluent or purified water present in a similar vessel and examined similarly (1). The International Conference on Harmonization (ICH) Q6A guideline on drug specifications recommends that "for dry products for injection, acceptance criteria for redispersibility or reconstitution time should be provided and the procedure for resuspension or reconstitution (mechanical or manual) should be indicated. Time required to achieve resuspension or reconstitution by the indicated procedure should be clearly defined" (2).