Biopharmaceutical drug design

F. L. Sorgi and H. Schreier. Non-viral vectors for gene delivery, Biopharmaceutical Drug Design and Development (S. Wu-Pong, and Y. Rojanasakul, eds.), The Hu-mana Press, Totowa, N.J., 1999, pp. 107-142. 

Biopharmaceutical Drug Design and Development Wupong, S., Ed. Humana Press, Inc. Totowa, New York, USA, 1999. 

I 6 H-bonding Parameterization in Quantitative Structure-Activity Relationships i Drug Design Tab. 6.5 Biopharmaceutics classification for 254 Drugs on the basis of HYBOT descriptors. 

LZ Benet. Biopharmaceutics as a basis for the design of drug products. In EJ Ariens, ed. Drug Design, Vol. 4. New York Academic Press, 1973, pp. 26-28. 

Kourounakis Rekka ADVANCED DRUG DESIGN AND DEVELOPMENT Labaune HANDBOOK OF PHARMACOKINETICS The Toxicity Asssessment of Chemicals Macheras, Reppas Dressman BIOPHARMACEUTICS OF ORALLY ADMINISTERED DRUGS Martinez PEPTIDE HORMONES AS PROHORMONES Rainsford ANTI-RHEUMATIC DRUGS Actions and Side Effects... 

More mechanistic studies in humans during Phase I must be performed for better feedback to discovery and pharmaceutical development, and thereby for faster performance through the clinical phases. It was recently suggested that a biopharmaceutical classification of drug permeability coefficients and dissolution issues must be determined early in the development program for rational drug design (Amidon 1996). 

At Brookhaven National Laboratory, New York, the Protein Data Bank (PDB) was established in 1971, and has become a repository for protein coordinates which are shared between scientists worldwide. The PDB is a very important tool and the basis for rational, stracture-based drug design -a prerequisite for the development of modern biopharmaceuticals. 

In short, drug design may be considered as an integrated whole approach which essentially involves various steps, namely chemical synthesis, evaluation for activity-spectrum, toxicological studies, metabolism of the drug, i.e., biotransformation and the study of the various metabolites formed, assay procedures, and lastly galenical formulation and biopharmaceutics. 

NFH Ho, HP Merkle, WI Higuchi. Quantitative, mechanistic and physiologically realistic approach to the biopharmaceutical design of oral drug delivery systems. Drug Deliv Ind Pharm 9 1111-1184, 1983. 

Yu, L. X., Lipka, E., Crison, J. R., Amidon, G. L., Transport approaches to the biopharmaceutical design of oral drug delivery system prediction of intestinal absorption, Adv. Drug Deliv. Rev. 1996, 19, 359-376. 

Kaplan, S. A., Biopharmaceutical considerations in drug formulation and design and evaluation, Drug Metab. Rev. 1972, 1, 15-34. 

The physicochemical and other properties of any newly identified drug must be extensively characterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins, a summary overview of the approach taken to initial characterization of these biomolecules is presented. A prerequisite to such characterization is initial purification of the protein. Purification to homogeneity usually requires a combination of three or more high-resolution chromatographic steps (Chapter 6). The purification protocol is designed carefully, as it usually forms the basis of subsequent pilot- and process-scale purification systems. The purified product is then subjected to a battery of tests that aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the QC identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5. 

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