The Path to Product Stability Is through Water

Many pharmaceutical processes are critically dependent on the amount of available or labile water in a system and less dependent on the total amount of water. The water activity of a product is intimately related to its tendency to degrade and to the growth of microorganisms in the product. In the introductory chapter of Water Activity Applications in the Pharmaceutical Industry, one of the editors states that controlling water activity below critical levels in a pharmaceutical product serves to maintain proper product structure, texture, flowability, density, and rehydration properties. Furthermore, knowledge of the water activity of pharmaceutical solids is important for understanding the scope of drug– excipient interactions and can provide insight into the physical problems of caking, clumping, collapse, and stickiness during product storage.

Water Activity Applications in the Pharmaceutical Industry, Anthony M Cundell and Anthony J. Fontana Jr., Eds., Parenteral Drug Association, Bethesda, MD, 2009, 291 pp., ISBN: 1-933722-33-9

The book's second chapter, "Water Activity: Fundamentals and Relationships," probably is the most important to pharmaceutical manufacturers because it provides detailed explanations of the underlying phenomena that labile water affects. This chapter contains a useful definition of water activity, a discussion of the energy of water in a system, and even tackles the difficulties of nonequilibrium systems. The author continues with a discussion of the effects of water activity on stability, chemical reactivity, physical properties, and microbial growth.

The third chapter covers water-activity determination and how it is affected by organizational bodies that set standards. Alhough the chapter is brief, it cites the most important regulatory documents.

The next three chapters cover topics of great interest to scientists engaged in formulation development. One of these examines the measurement methods suitable for the determination of water activity (e.g., chilled-mirror dewpoint and electric hygrometers). The chapter also covers the important topic of determining moisture-sorption isotherms with static desiccator methods, dynamic vapor sorption, and dynamic dewpoint methods, as well as methods for the measurement of moisture content.

A subsequent chapter summarizes the important topics of water-activity management and the determination of water activity in research and quality control. Its discussion is followed by case examples such as determining the sorption characteristics of sugar spheres, and developing transportation practices that prevent damage to products in transit. Although it leaves little to be desired, the chapter should have appeared earlier in the book to maintain an emphasis on pharmaceutical formulation development.

The book's remaining chapters are given over to expositions of the relationship between water activity and microorganisms. Specialists interested in these topics will find a considerable amount of useful information here.

The pharmaceutical industry would doubtless benefit from the food industry's deep degree of understanding about water activity. Preformulation scientists certainly should be able to integrate measurements of water activity into their programs of study to make observed trends more comprehensible. Because labile water is typically the enemy of formulation stability, any program that includes the study of water activity will be improved by the effort. The present volume goes a long way toward providing the background needed to initiate such work.

Harry G. Brittain is an institute director at the Center for Pharmaceutical Physics, 10 Charles Rd., Milford, NJ 08848, tel. 908.996.3509, fax 908.996.3560, hbrittain@embarqmail.com. He also is a member of Pharmaceutical Technology's Editorial Advisory Board.