General Considerations on excipients
Excipients are a chemically diverse group of materials, and including all states of matter (solid, liquid, gas and semi-solid). Some may be manufactured using batch processing, but many are manufactured using continuous processing. The scale of excipient manufacture is often much larger than for an API or finished product. In addition, very few excipients are manufactured exclusively for pharmaceutical use. Very often, the pharmaceutical usage of an excipient may represent a minor fraction of the other industrial uses.
Excipients are included in pharmaceutical finished products to overcome some of the limitations of the active pharmaceutical ingredient(s) (APIs) concerning the manufacture and stability of those products, and to facilitate their use and release and/or delivery of the drug after administration to the patient.
The number of nominally single ingredient pharmaceutical excipients is limited. There are gaps in the range of performance attributes (functionality) available from single ingredient excipients. The introduction of novel chemical excipients is both lengthy and economically risky.3,4,5 Co-processed excipients provide a means whereby new excipient functionality can be introduced without the time and economic constraints relating to the introduction of novel chemical excipients.
As with other excipients, co-processed excipients may be manufactured using either batch or continuous processing. The requirements for safety and consistency of performance (variability) are the same for either type of processing.
A co-processed excipient is not a simple blend. Co-processed excipients are defined as follows:
A co-processed excipient is a combination of two or more compendial or non-compendial excipients designed to physically modify their properties in a manner not achievable by simple physical mixing, and without significant chemical change. However, in some instances, formation of necessary components may occur, such as in-situ salt formation.
From this definition, it can be seen that the key elements to be addressed by both the manufacturer and the excipient user are the composition of the co-processed excipient, and confirmation that the processing does indeed produce only a physical interaction, such as hydrogen bonding or ionic association, rather than a covalent chemical combination. In addition, as with any ‘new’ material there will need to be an assessment of the risk to patient safety when the excipient is intended for use in pharmaceutical products for human or veterinary use. Investigations to justify the ratio of ingredients, the necessary processing, and safety of the co-processed excipient, will need to be undertaken before the novel co-processed excipient is launched for commercial sale. The user of any co-processed excipient is responsible for assuring its fitness for purpose, and that the co-processed excipient and its components are manufactured to acceptable standards of good manufacturing practice (GMP).