David P.Elder
Principal Consultant
D.P.Elder Consultancy
Hertford, United Kingdom

Abstract

Excipients play a key role in defining the quality, processability and the bioavailability of the drug product. However, they are commodity chemicals, manufactured at large scale often using continuous processes. Excipients exhibit variability arising from (i) source-to-source, (ii) manufacturer-to-manufacturer, and (iii) lot-to-lot differences. Regulatory authorities and pharmacopoeias have stressed the importance of understanding this variability and its impact on product quality. However, attempts to fully describe their physical characteristics using functionality or performance testing have met with limited success because those material attributes could be critical in one drug product, but totally irrelevant in another. Thus, excipient performance tests are application specific, linked to each different formulation and process, and it is difficult, if not impossible for these tests to cover all potential eventualities.

INTRODUCTION

Excipients are typically defined as any supplementary component(s) of the dosage form other than the drug substance. Excipients constitute the largest percentage of any dosage form and are added as functional constituents enhancing manufacturability, and/or stabilising constituents. Excipients are now recognised as playing an important role in enhancing the bioavailability by modifying the drug’s solubility and/or permeability (1).

MANUFACTURE OF EXCIPIENTS

Excipients tend to be large scale, commodity chemicals that are used in cosmetics, foodstuffs, industrial chemicals, as well as the pharmaceutical industry. Indeed, the latter represents only a small fraction of the overall manufacturing volumes, e.g. lactose; which restricts the end user’s ability to influence the required quality of the excipient (2). Additionally, excipients aren’t always manufactured according to current good manufacturing practice (cGMP), prompting the EU (3) to introduce a risk-based initiative to assess the most appropriate level of cGMP for its intended purpose. Excipients can be produced by batch or continuous processing. He ...