Quality and functionality of excipients

The quality of medicines depends not only on the active principles and prod uction processes, but also the performance of the excipients. The tradition al concept of the excipient as any component other than the active substanc e has undergone a substantial evolution from an 'inert' and cheap vehicle t o an essential constituent of the formulation. The rapid evolution of scien tific, regulatory and economic factors, the introduction of delivery system s and the advance in biopharmaceutics have led to a new interest in the rol e and functionality of the excipients. More than one thousand raw materials are available from a multitude of sources and are used today in the pharma ceutical industry. Their chemical structures vary from small molecules to c omplex natural or synthetic polymeric mixtures. Excipients are now chosen t o perform a variety of functions to guarantee the stability and bioavailabi lity of the drug substance from the drug product and its manufacturability on a production scale. Beyond the dosage form necessities, excipients are r equired to perform important and specific technological functions, particul arly in the case of solid dosage forms. As a consequence, their characteris ation must go beyond the simple tests for identity, purity and strength as prescribed in general by the Pharmacopoeia monographs. With the exception o f the Textbook of Pharmaceutical Excipients, not many reference sources des cribing the physical mechanical characteristics of the powders for a specif ic role are available. Full physical characterisation of solid materials is now made possible with the help of high resolution analytical techniques o n the molecular, particulate and bulk levels. This systematic approach is n ecessary to guarantee the behaviour of the excipient during the formulation and production phases. Some examples have been chosen in this mini-review in an effort to highlight the emerging trends in the development of 'tailor -made' materials. Three main approaches are followed by the industry: physi cal or minor chemical manipulation of materials already known, combination of two or more marketed excipients in order to reduce unwanted defects and, finally, preparation of new chemical entities with huge investments for th e toxicity studies. Excipient harmonisation, standardised functionality tes ts, preformulation data bases and expert systems will contribute to change the conventional trial-and-error formulation approach into a far more scien tific and technological development. (C) 1999 Elsevier Science S.A. All rig hts reserved.