Quality and functionality of excipients.

The quality of medicines depends not only on the active principles and production processes, but also the performance of the excipients. The traditional concept of the excipient as any component other than the active substance has undergone a substantial evolution from an 'inert' and cheap vehicle to an essential constituent of the formulation. The rapid evolution of scientific, regulatory and economic factors, the introduction of delivery systems and the advance in biopharmaceutics have led to a new interest in the role and functionality of the excipients. More than one thousand raw materials are available from a multitude of sources and are used today in the pharmaceutical industry. Their chemical structures vary from small molecules to complex natural or synthetic polymeric mixtures. Excipients are now chosen to perform a variety of functions to guarantee the stability and bioavailability of the drug substance from the drug product and its manufacturability on a production scale. Beyond the dosage form necessities, excipients are required to perform important and specific technological functions, particularly in the case of solid dosage forms. As a consequence, their characterisation must go beyond the simple tests for identity, purity and strength as prescribed in general by the Pharmacopoeia monographs. With the exception of the Textbook of Pharmaceutical Excipients, not many reference sources describing the physical mechanical characteristics of the powders for a specific role are available. Full physical characterisation of solid materials is now made possible with the help of high resolution analytical techniques on the molecular, particulate and bulk levels. This systematic approach is necessary 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: physical 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 the toxicity studies. Excipient harmonisation, standardised functionality tests, preformulation data bases and expert systems will contribute to change the conventional trial-and-error formulation approach into a far more scientific and technological development.