Comparison of excipients in approved parenteral products and their maximum daily exposure values

Abstract

The following article analyses the excipients used in the parenteral formulations registered by the FDA in the years 2011 and 2021. It adds real word data for parenteral excipients in approved products from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) and Irish Health Products Regulatory Authority (HPRA) in 2021. Maximum daily exposure (MDE) for all parenteral excipients which had their amount listed either in the Medsafe or HPRA database is presented. Altogether, there were 355 excipients found in the parenteral dosage forms across all markets (US, New Zealand, Ireland). Only 90 excipients (25.3%) were found in all three markets. In contrast there were 187 (52.7%) excipients found in only one market. The maximum daily exposure values of parenteral excipients from New Zealand and Ireland are frequently higher than the values found in the IID, adding important new information when the toxicity of these excipients is considered. There is a heterogenicity between the markets in use of parenteral excipients, with US market leading in the number of total excipients as well as excipients present only in the US market. Nevertheless, there are several excipients not found in the US market but are registered in other markets. Comprehensive listing of parenteral excipients used worldwide presented in this article enables formulation scientist to quickly reference all potential parenteral excipients which are already proven safe and acceptable, when designing as new parenteral formulation. Further, a list of new values for MDE, often higher than those listed in the IID, provides important information for the formulation scientist and toxicologists about the potential toxicity of these excipients.