Dissolving the Insoluble

Through methods such as combinatorial chemistry and high-throughput screening, far more drug candidates than ever before are being produced. Unfortunately, many of these candidates have an undesirable property. As editor Rong Liu says in the first line of Water-Insoluble Drug Formulation, "These new compounds, like rocks, never dissolve in water."

Developing delivery systems for drug candidates with poor water solubility is one of the most difficult problems pharmaceutical product-development scientists face today. Liu's book is an outstanding contribution to understanding and solving this problem.

The volume contains 23 chapters from 40 contributors. The authors are well-credentialed experts who have extensive academic, industrial, or regulatory experience in drug-product formulation and development.

The book is logically organized. Chapters 1–5 introduce basic principles (e.g., solubility theory and prediction), preformulation aspects of insoluble compounds, and these compounds' pharmacokinetic behavior. Chapter 6 addresses the regulatory aspects involved in the dissolution testing of low-solubility drug products.

Chapters 7–19 address the strategies that may be taken to address this problem, including complexation, cosolvents, emulsions, microemulsions and lipid-based delivery systems, micellization, liposome technology, salt formation, prodrug approaches, particle-size reduction, solid-state dispersions, and modification of the solid state of the drug substance.

Two chapters about lipid-based drug-delivery systems are exceptionally well written. Extensively referenced, these chapters provide a useful integration of theory and practice. Helpful tables include information such as a list of approved lipids for parenteral lipid-based formulations, lists of commercial products and their composition, referenced lists of experimental studies with comments, and the probable effects of different variables.

The formulation strategy section is followed by chapters that discuss powder technology, soft-gelatin capsule development, the development of oral modified-release delivery systems for insoluble compounds, and the scalable manufacture of water-insoluble drug products.

Aside from the chapter on developing modified-release dosage forms, these chapters largely focus on manufacturing science and technology. Including manufacturing information is appropriate because the technology complements the formulation science that is described earlier in the book. The manufacturing information makes the book more complete than it otherwise would have been.

The chapter about powder technology serves as a vehicle by which to introduce the US Food and Drug Administration's process analytical technology (PAT) initiative. This chapter explains the concept of quality by design, as opposed to attempting to test quality into the product, and offers several examples of how a mechanistic or fundamental understanding of product and process contributes to achieving that end.

The problem with Water-Insoluble Drug Formulation is that the treatment of certain topics seems compressed and, at times, superficial. Given that whole books have been written on various technologies and scale-up, for example, this shortcoming should not be surprising. This book's main subject is formulating with insoluble compounds. Readers will need to consult other sources about related topics such as manufacturing and unit operations if they have no background in those areas.

The authors amply illustrate their points by including many clear figures and useful data tables. Despite the large number of contributors, the chapters adhere to the mission of the book quite consistently. In addition, the chapters examine their subjects in comparable depth. Constructive overlap occurs between certain chapters, and it is useful to the reader.

This book would be of value to anyone involved in research or development who is concerned with developing successful delivery systems for water-insoluble drug compounds. The book would also be an excellent resource for educators.

Larry L. Augsburger is professor emeritus of pharmaceutical sciences at the University of Maryland School of Pharmacy, 20 North Pine St. Baltimore, MD 21201-1180, tel. 410.706.7615, laugsbur@rx.umaryland.edu