Breaking Down Barriers to Oral Delivery

Published on: 
Pharmaceutical Technology, Pharmaceutical Technology-02-02-2010, Volume 34, Issue 2

A recent book provides information about formulating biopharmaceuticals that is easy to swallow.

The oral delivery method is by far the most prevalent route of administration for pharmaceuticals. It is preferred by patients and physicians throughout the world. Oral delivery of biopharmaceuticals, however, poses significant logistical and formulation problems. Most biopharmaceuticals, including proteins, enzymes, and nucleic acids, are susceptible to attack by the human body's digestive and defense systems. This highly desirable route of administration is therefore extremely challenging for large-molecule drugs.

Oral Delivery of Macromolecular Drugs provides tools that allow a reader to understand the problems associated with the delivery of macromolecules through the gastrointestinal (GI) tract. The book also offers a fairly comprehensive set of strategies to overcome these problems.

Most of the book can be likened to an extensive, organized, comprehensive, and well-executed review article. Its 12 chapters are written by different authors, but the topics are approached so consistently, and the sections so well integrated, that the book often seems like it was written by a single author.

Oral Delivery of Macromolecular Drugs: Barriers, Strategies and Future Trends, Andreas Bernkop-Schnürch, Ed., Springer, Berlin, 2009, 242 pp., ISBN: 978-1-4419-0199-6


The text begins with three exceptional chapters that are worthy of rereading on a regular basis and should be of interest even to formulators who work with small molecules. These chapters deal with the barriers to delivering intact proteins through the GI tract. They are classified as enzymatic barriers, mucus-gel barriers, and absorption barriers, and each is described in its own chapter.

The authors of these chapters present a brief but comprehensive collection of accumulated knowledge, including hundreds of references, of GI physiology that affects drug uptake. For example, the chapter about enzymatic barriers presents information about the function of digestive enzymes, including descriptions of typical peptidases, nucleases, and other proteins. This chapter also explains which enzymes are likely to be found in the stomach, the lumen of the small intestine, the cellular lining of the small intestines, and the colon.

This systematic identification of the barriers continues through the next two chapters. Chapter Two sketches the constituents of the GI tract's mucosal layer with exquisite detail. The third chapter examines the transcellular diffusion and transport mechanisms of the cells found on the walls of the GI tract.

The next seven chapters focus on approaches that overcome the barriers described in the first chapters. The text encompasses basic and well-understood techniques and somewhat more abstract and innovative strategies. In this portion of the book, the reader will find information about techniques such as chemical modification, using enzyme inhibitors, adding permeation enhancers, and overcoming cellular efflux pumps.

Subsequent chapters cover formulation options such as excipient selection, micro- and nanotechnology carriers, and liposomal carriers. Each of the sections includes a well-written description of the relevant biochemistry and the expected outcomes. Well-chosen references allow readers to pursue likely solutions for their problems. The final two chapters focus on two special classes of macromolecules, vaccines and nucleic acids, and their special needs.

All of the chapters include useful and well-labeled graphics. Tables provide comparative details and experimental data to clarify the subjects of discussion. These tables are clearly described in the body of the text. The references are recent and point to major findings rather than singular, successful experiments. The text is clearly written by experts in their respective fields.

Overall, Oral Delivery of Macro-molecular Drugs presents a lot of information in an inviting format. The text is well-written and documented. This book should find its way into the hands of formulators of both small and large molecules. Because of its concise presentations, it should be a welcome addition for students and formulators who are new to the field. It also should serve as an exceptional reference for experienced formulators.

Todd L. Cecil, PhD, is vice-president of compendial sciences at the Us Pharmacopeia, 12601 twinbrook Pkwy., rockville, mD 20852-1790, tel. 301.816.8234, He also is a member of Pharmaceutical Technology's editorial advisory Board.