Designing and Delivering Therapeutic Proteins

The discovery, use, and development of protein therapeutics has increased opportunities for drug-product development. Advancing the therapeutic potential of these protein-drug entities presents a challenge to formulation and delivery scientists.

Nusrat Motlekar

The second edition of Protein Formulation and Delivery presents an updated review of recent research in the formulation and delivery of therapeutic proteins and peptides. The book contains expanded sections about protein characterization and formulation and several new chapters that focus on protein delivery.

One of the book's new chapters offers information to aid the rational choice of excipients for use during the freeze-drying process. The chapter also provides sound practical advice about bulking agents, buffers, and simple tests to predict the stability of freeze-dried formulations.

Two case studies of recombinant proteins are discussed in another new chapter about the preformulation development of protein drugs. The case studies illustrate the procedures for solubility and stability-screening studies for recombinant proteins.

Other new chapters present recent developments in protein-drug delivery. The chapter entitled "Formulation of Leuprolide at High Concentration for Delivery from a One-Year Duration Implant" explains the method of using depot systems for injectables. A chapter called "Oral Delivery of Biopharmaceuticals Using the Eligen Technology" examines carrier-mediated systems for delivery of an oral insulin formulation.

Information about products that use a novel approach to the parenteral delivery of proteins (e.g., needle-free injectors) is also offered in a new section that includes a wealth of information for formulators. The section describes emerging technology that provides noninvasive delivery of protein therapeutics. Topics include formulation and clinical considerations for needle-free delivery and information about needle-free injector products currently in development.

Another new chapter discusses the specifications and expiration dating of biotechnology products. Concise tables illustrate physicochemical-characterization test procedures and the acceptance criteria for biotechnological drugs and products.

The final chapter is about the similarities and differences between protein biologics and small synthetic molecules. This section provides a useful introduction to the complexities of proteins, compared with conventional chemical drugs.

The book's remaining chapters have been updated for the second edition. The revised chapter about freeze-drying provides an excellent overview of the basics of the lyophilization process. It also addresses problems encountered in the storage and reconstitution of lyophilized proteins.

Protein Formulation and Delivery, Second Edition, Eugene J. McNally and Jayne E. Hastedt, Eds., Informa Healthcare, New York, NY, 2007, 376 pp., ISBN 9780849379499.

Other topics that are examined include the causes and mechanisms of protein instability in formulation development, the analytical techniques used in protein stability assessment, and solution formulations of proteins and peptides. For the reader's convenience, the section about protein and peptide stability is divided into two discrete chapters that address physical and chemical considerations separately. This arrangement creates a more logical flow than the book's first edition.

A few shortcomings detract from the text. One flaw is that important content is excluded. For example, a mention of the pharmacokinetics of therapeutic peptides and proteins would have been useful to metabolism and pharmacokinetics scientists. Some important aspects of pharmaceutical technology such as an outline of alternative methods for the mucosal delivery of therapeutic proteins and vaccines would have been helpful as a starting reference point for novices.

Also, the book lacks coverage of particulate delivery systems that target peptide and protein drugs, oligonucleotides, and genes.

Despite containing typographical errors, the book is generally well written. The second edition is a valuable guide for the beginner who seeks an overview of literature before turning to more detailed primary sources. Although directed toward formulation scientists, this book would also be useful reading for graduate students and faculty involved in any aspect of protein delivery.

Nusrat Motlekar is an assistant professor at Butler University, 4600 Sunset Ave., Indianapolis, IN 46240, tel. 317.940.6427, fax 317.940.3046 nmotleka@butler.edu