Characterization and Applications of Colloidal Systems as Versatile Drug Delivery Carriers for Parenteral Formulations

Excipients are inactive ingredients that are intentionally added to pharmaceutical dosage forms and are not intended to exert a therapeutic effect. Most of the formulations contain a small percentage of the active drug and typical major components are additives. Due to safety reasons, there are limitations on the type and quantity of an additive to be included in an injectable drug formulation. Commonly used excipients in the formulation of submicron emulsion/suspension are: buffering agents, tonicity agents, preservatives, wetting agents, complexing and dispersing agents, solvents and co-solvents, etc. Selection of excipients depends on toxicity issues, pharmaceutical acceptability of additives and excipients’ ability to withstand terminal sterilization and aseptic processing. The choice of additives also depends on:

• Drug-excipient compatibility.
• Compatibility of the excipient with manufacturing process and container–closure system.
• Excipient impact on quality, safety, and effectiveness of the drug product.
• Route of administration.
• Dose volume and intended use of the drug product: single versus multiple dose.

IPEC (International Pharmaceutical Excipients Council) has classified excipients into the following three classes based on the availability of safety information:

• New chemical excipients: A full safety evaluation program is required for these excipients. A drug master file (DMF) must be filed with the FDA for a new excipient. The DMF contains relevant safety information.
• Existing chemical excipients—first use in man: Animal safety data are available for this class of excipients. Additional safety information is required when there is a change in dosage form, route of administration, higher dose, etc.
• New modifications or combinations of existing excipients: This class of excipients indicate a physical reaction and not a chemical reaction. Thus, no additional safety evaluation is necessary.

The FDA has published a list of substances in the Code of Federal Regulations that are generally regarded as safe (GRAS). Besides, the FDA maintains a list of inactive ingredients entitled the inactive ingredient guide (IIG) that are approved and can be incorporated into drug products. The IIG mentions a list of the maximum amount of excipients that can be incorporated in to drug products intended for a specific route of administration. Excipients are an integral part of drug formulation; however, the FDA does not currently have any process to separately evaluate the safety of the inactive ingredients. Rather, the excipients are reviewed and approved as “components” of drug/biologic product in the application. This regulatory process is suitable from a scientific viewpoint Table 1 below mentions a list of some commonly used excipients approved by the FDA (https://www.accessdata.fda.gov/scripts/cder/iig/index.Cfm) and the maximum allowable amount per unit dose used in formulation of colloidal drug delivery systems (DDS) as per the Inactive Ingredient Guide (IIG):