Biopharmaceutics System

As in all other areas of scientific inquiry, if one can interpret collected data, there is often value added in the collection of relevant data beyond that considered sufficiently compelling. It is also within the realm of possibility that the described methods for assessing species relevance may provide conflicting data. In such an instance, preference would be given to data derived from the higher order, intact biopharmaceutical systems. 

Gonzalez, M. Materials of construction for biopharmaceutical systems. ASME Bio Process Seminar, San Juan, PR, Jan... 

Four column systems are available from Amersham Pharmacia Biotech that can be used to pack SEC media for various applications at the laboratory scale. These include C, XK, SR, and HR column systems. All of the laboratory-scale columns are constructed with borosilicate glass tubes. Columns for larger scale process applications include INdEX, BPG, EineLINE, BPSS, and Stack columns. The larger scale columns are constructed to meet stringent validation requirements for the production of biopharmaceuticals. Each of the column types are described. 

Purification of biopharmaceuticals often involves the removal of materials with physical characteristics very similar to the desired product, such as failure sequences from DNA synthesis or misfolded proteins from bacterial fermentations. The contaminants, however, may have biological characteristics very different from the desired product, including different antigenicities, bioactivities, and specificities. There are even systems in which the... 

Fig. 12 Illustration of the Biopharmaceutical Classification System (BCS), which classifies drug absorption potential on the basis of aqueous solubility or membrane permeability. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

Bioavailability depends not only on having the drug in solution, but also on the drug s permeability. A jejunal permeability of at least 2-4 x 10 4cm/s, measured in human subjects by intubation, is considered high [97]. For many drugs and other substances, this permeability corresponds to a fraction absorbed of 90% or better. Amidon et al. [97] thus proposed a Biopharmaceutics Classification System (BCS) for drugs based on the above definitions of these two parameters. Table 3 defines the BCS and includes some drugs representative of each class. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

A. S. Harris, Biopharmaceutical aspects of the intranasal administration of peptides, in Delivery Systems for Peptides (S. S. Davis, L. Ilium, and E. Tomlinson, eds.), Plenum Press, New York, 1986, p. 191. 

Figure 2.9 Biopharmaceutics classification system [101-110]. Examples are from Refs. 102 and 104. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

FDA Guidance for Industry Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties/ Active Ingredients Based on a Biopharmaceutics Classification System, CDER-GUID 2062dft.wpd Draft, Jan. 1999. 

Lentz, K. A. Hayashi, J. Lucisano, L. J. Polli, J. E., Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system, Int. J. Pharm. 200, 41-51 (2000). 

AC ADME ANS AUC BA/BE BBB BBM BBLM BCS BLM BSA CE CHO CMC CPC CPZ CTAB CV DA DOPC DPPC DPPH aminocoumarin absorption, distribution, metabolism, excretion anilinonaphthalenesulfonic acid area under the curve bioavailability-bioequivalence blood-brain barrier brush-border membrane brush-border lipid membrane biopharmaceutics classification system black lipid membrane bovine serum albumin capillary electrophoresis caroboxaldehyde critical micelle concentration centrifugal partition chromatography chlorpromazine cetyltrimethylammonium bromide cyclic votammetry dodecylcarboxylic acid dioleylphosphatidylcholine dipalmitoylphosphatidylcholine diphenylpicrylhydrazyl... 

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. 

Fig. 7.5. The Biopharmaceutics Classification System (BCS) provides a scientific basis for predicting intestinal drug absorption and for identifying the rate-limiting step based on primary biopharmaceutical properties such as solubility and effective intestinal permeability (Pefr). BCS serves as a product control instrument. The BCS divides drugs into four different classes based on their solubility and...

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