Emerging Excipients in Parenteral Medications

fines excipients as “substances, other than the active drug substance of finished dosage form, which have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing of the drug delivery system during its manufacture; protect; support; enhance stability, bioavailability, or patient acceptability; assist in product identification; or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use” (1). This definition implies that excipients serve a purpose in a formulation and contrasts with the old terminology, inactive excipients, which hints at the property of inertness. With a literal interpretation of this definition, an excipient can include diverse molecules or moieties such as replication incompetent viruses (adenoviral or retroviral vectors), bacterial protein components, monoclonal antibodies, bacteriophages, fusion proteins, and molecular chimera. For example, using gene-directed enzyme prodrug therapy, research indicated that chimera containing a transcriptional regulatory DNA sequence capable of being selectively activated in mammalian cells was linked to a sequence that encodes a -lactamase enzyme and delivered to target cells (2). The expressed enzyme in the targeted cells catalyzes the conversion of a subsequently administered prodrug to a toxic agent. A similar purpose is achieved by using an antibody conjugated to an enzyme followed by the administration of a noncytotoxic substance that is converted in vivo by the enzyme to its toxic form (3). In these examples, the chimera or the enzyme-linked antibody would qualify as excipients. Furthermore, many emerging delivery systems use a drug or gene covalently linked to the molecules, polymers, antibody, or chimera responsible for drug targeting, internalization, or transfection. Conventional wisdom dictates that such an entity be classified as the active substance or prodrug for regulatory purposes and be subject to one set of specifications for the entire molecule. The fact remains, however, that only a discrete part of this prodrug is responsible for the therapeutic effect, and a similar effect may be obtained by physically entrapping the drug as opposed to covalent conjugation. The situation is further complicated when fusion proteins are used as a combination of drug and delivery system or when the excipients themselves