Book Reviews

Book Review - Handbook of Pharmaceutical Excipients 7th Edition

Handbook of Pharmaceutical Excipients 7th Edition

Reviewer: Iain Moore

Excipients may well have no therapeutic effect in pharmaceutical dosage forms, but they are anything but innocent. Their inclusion is an essential part of the safe and effective delivery of the active ingredient to the patient. It is critical therefore that not only the properties of the excipients are understood but also the safety, interactions and typical functionality of excipients are known. Selection of excipients is therefore critical to the successful realisation of the medicinal product. The Handbook of Pharmaceutical Excipients has established itself as a leading reference work to acid this activity.

The 7th edition of this Handbook now includes over 350 excipient monographs and the majority are recently revised to bring them up to date. So will the Handbook be able to help excipient users identify the optimum excipient from the hundreds available? At first view the consistent layout and structure is reader friendly and provides an excellent reference point. The tables listing the properties of families of excipients are particularly useful and informative, as is the comparisons of the various compendial requirements.

But the devil is in the detail, and this is where the consistency of the monographs can be variable. The quality of the individual monographs relies upon the expertise and knowledge of the individual writers, and the goodwill of the manufacturers and suppliers of the excipients to provide accurate and up to date information to the authors. Some monographs are regional centric and so omit information relevant to other regions.

For example in the poloxyethylene stearates monograph reference is made to the fact that typical residual levels of free ethylene oxide should be less than 100ppm and that where provided in bulk with residual levels in excess of 100ppm there is an explosion hazard from the free ethylene oxide in the headspace of the package (not to mention a toxic inhalation threat as well). Additionally the compendial specifications for this class of product from the European Pharmacopoeia specifications are not included in the table of compendial specifications in which case the stricter limits of 1ppm max free ethylene oxide would have been apparent. Additionally no mention is made of residual 1,4 dioxane levels, a toxic impurity in this class of product, which is again limited in the European Pharmacopoeia monographs.

For the oleochemical based monographs I would also prefer to see greater emphasis on the fact that the molecular weight as well as the empirical and structural formulas are indicative values only. Readers could be mislead in thinking that these values are definitive when many of these excipients are made with fatty acids or fatty alcohols that are mixtures of different carbon chain length components. Some monographs acknowledge this better than others.

The details on the method of manufacture are rather vague and do not therefore provide the reader with enough information to begin to assess the impurities or processing aids that may remain in the product. For example catalytic hydrogenation of triglycerides is referenced in the manufacture of cetyl alcohol, the reader would have to conduct further investigations with specific manufacturers to identify which catalysts are commonly used and so may be present in the excipient. This should happen as part of supplier and excipient qualification of course, and this is where a reference work such as this can help users of excipients, by pointing them to the key questions to ask their suppliers. Not all suppliers will volunteer the information perceiving to be confidential.

The section in each monograph on regulatory status is particularly useful as it indicates if the excipient is listed in the FDA inactive ingredients database and in what kind of applications as well. This sets precedence of use for the excipient and would suggest use of that excipient in similar applications would be low risk.

The section on handling precautions appears to be taken from material safety data sheets and should be interpreted accordingly in terms of the precautions needed when handing these materials in large quantities in an industrial environment. In some cases however they refer to the inhomogeneity of the product and therefore reflect prudent precautions to be applied when dispensing the excipient. This is a very valuable additional detail.

Some details on published safety studies are included, although a lot of these references are now quite old and so may not be representative of the quality of material available from today’s suppliers (cf residual ethylene oxide levels in poloxyethylene stearates).

It must be challenging to keep the appendices accurate and up to date in terms of which supplier offers which tradename of excipient. In this regard it would be helpful for the suppliers themselves to validate the details on their entries. The Index in this regard is incomplete with some tradenames being listed and referenced to the monographs and others not. In addition the all-important cross-reference to the supplier in Appendix 1 – Suppliers Directory is missing from the excipient appendix. However in this electronic age this is less important than in pervious times as a simple Internet search will often provide the necessary linkages between a tradename and a supplier.

The knowledgeable reader will not have any issues with these minor observations and indeed will take these points as exactly the questions to be asking their supplier during qualification.

The Handbook is an essential companion to the compendia that define the specifications required for an excipient. There is no better or succinct source of information on excipients and the editors and authors are to be credited with producing such a valuable reference work.


Iain Moore

Global Head of QA

Croda Europe Ltd