Excipients for parenteral dosage forms: regulatory considerations and controls
INTRODUCTION A survey of commercial parenteral products confirms an interesting observation-the active drug molecule typically comprises only a small percentage of the drug product formulation whereas the excipients make up the primary components. Excipients provide the enhanced vehicle for the active pharmaceutical ingredient (API) and are typically referred to as inactive or inert ingredients, where “inactive” or “inert” indicates the compound does not directly contribute to the intended therapeutic or diagnostic activity of the drug product. Pharmaceutical excipients or additives are compounds added to the finished drug product with a specific functional role [other than that defined for API or in case of biologics, drug substance (DS)]. These functions include increasing the bulk to aid in manufacturing, stabilizing of the active drug, improving delivery and targeting, and modifying the safety or pharmacokinetic profile of the active drug. Compounds considered excipients also encompass ingredients that are used for the production of dosage forms, but may or may not be present in the finished dosage forms. Examples are water for lyophilized product and inert gases in the head space of container (1). It is clear that excipients have a “functionality” in the dosage form synonymous to the pharmacological activity of API/DS, which is currently being acknowledged by various pharmacopoeias (2). It is noted, however, that many of the existing excipient monographs do not address this functionality aspect and its control.