Biopharmaceutics classification system classes

Table 2 Some Examples of Drugs in Biopharmaceutical Classification System Classes...

Figure 1 Summary of the suitability of various formulation strategies to drugs in individual Biopharmaceutical Classification System classes.

EXCIPIENTS USED TO ENHANCE DISSOLUTION OF BIOPHARMACEUTICAL CLASSIFICATION SYSTEM CLASS II AND IV DRUGS... 

Table 4 The Dissolution and Release of Biopharmaceutical Classification System Class II and IV Drugs Are Enhanced by Hydrophilic Excipients...

Jantratid, E., Prakongpan, S., Amidon, G.L. and Dressman, J. (2006) Feasibility of biowaiver extension to biopharmaceutics classification system class III drug products cimetidine. Clinical Pharmacokinetics, 45 (4), 385—399. 

For pharmaceutical products containing Biopharmaceutics Classification System Class I (highly soluble, highly permeable) APIs... 

Table 3 The Effect of Hydrophilic Excipients on the Dissolution Rates of Griseofulvin (a Biopharmaceutical Classification System Class II Drug)...

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. 

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...

Biopharmaceutics Classification System Redefining BSC Solubility Class Boundary... 

Fig. 15.5. The biopharmaceutics classification system (BCS). Drug-like molecules are grouped into four BCS classes based on their solubility and permeability. A drug is regarded as a highly soluble compound if the maximum dose given orally is soluble in 250 mL fluid in the...

The example of amprenavir, an HIV-1 protease inhibitor, shows that intestinal metabolism can also be used as a strategy to enhance the bioavailability of compounds. In the biopharmaceutics classification system (BCS), amprenavir can be categorized as a class II compound it is poorly soluble but highly permeable [51]. Fosamprenavir, the water-soluble phosphate salt of amprenavir, on the other hand, shows poor transepithelial transport. However, after oral administration of fosamprenavir, this compound is metabolized into amprenavir in the intestinal lumen and in the enterocytes mainly by alkaline phosphatases, resulting in an increased intestinal absorption [51, 174],... 

The publication of the U.S. FDA Guidelines allowing the waiver of bioequivalence study for compounds classified as Class I based on the Biopharmaceutics Classification System... 

Waiver of in vivo bioequivalence studies for major post approval manufacturing changes for the BCS Class I (Biopharmaceutics Classification System highly soluble, highly permeable and rapidly dissolving) solid oral products is NOT recommended for narrow therapeutic index drugs (17). 

Blume HH, Schug BS. The biopharmaceutics classification system (BCS) class III drugs-better candidates for BA/BE waiver Eur J Pharm Sci 1999 9 117-121. 

Following oral administration, dissolution of the drug molecule in the intestinal milieu is a prerequisite for the absorption process. According to the Biopharmaceutical Classification System (BCS) [2], poor water-soluble compounds (i.e., aqueous solubility less than 100 pg/ mL) are class 2 or class 4 compounds. For class 2 compounds, the absorption level is dictated by the dissolution properties of the molecule in the gastrointestinal (GI) fluids. BCS class 4 compounds, which are characterized by both low solubility and poor intestinal wall permeability, are generally poor drug candidates (unless the dose is very low). 

The Biopharmaceutics Classification System (BCS)3 defines four classes of compounds based upon solubility and permeability. Particle size and size distribution... 

With the advent of new biotechnological techniques endogenous compounds like insulin, buserelin or octreotide have become available at affordable prices. All of these substances still have to undergo needle application. Until today the development of alternative delivery systems for the nasal, buccal, peroral, rectal and pulmonary routes for the administration of those class III drugs according to the biopharmaceutics classification system (BCS) (Amidon et al. 1995) could not keep pace with this development of endogenous compounds or is not economic enough for the health care payers (e.g. insulin application via the pulmonary route). 

Figure 6.16 The Quantitative Biopharmaceutics Classification System (QBCS) utilizes specific cutoff points for drug classification in the solubility-dose ratio (1/0), apparent permeability (Papp) plane. Each class of the QBCS can be characterized on the basis of the anticipated values for the fraction of dose absorbed, Fa and the fraction of dose dissolved, at the end of the dissolution process assuming no interplay between dissolution and uptake. In essence the classification system is static in nature.

Aqueous solubility of ionizable molecules at different pH values is an important characteristic because it indicates the potential substance behavior in the stomach and intestinal tract and its potential impact on bioavailability. Moreover, it also provides important information for formulation scientists to define the class of a drug substance in the Biopharmaceutics Classification System (BCS), a regulatory guidance for bioequivalence studies. The BCS is a scientific framework proposed by the FDA to classify drug substances based on their aqueous solubility and intestinal permeability and defines important parameters in the selection of drug candidates into development. According to the BCS, drug substances are classified as shown in Table 12-4. 

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