Solubility biopharmaceutics classification system

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.)...

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...

Based on their solubility and intestinal permeability characteristics, drugs have been classified into one of four categories according to the Biopharmaceutics Classification System (BCS) proposed by Amidon et al. [49]. 

Biopharmaceutics Classification System Redefining BSC Solubility Class Boundary... 

Tab. 8.2. Biopharmaceutics Classification System (BCS). BCS is a permeability and solubility classification.

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],... 

Since solubility and permeability are the two most important factors influencing oral absorption of drugs, the following biopharmaceutical classification system (BCS) for drug substances, based on the work by Amidon et al.,67 has been recommended by the FDA 68... 

Yazdanian, M., Briggs, K., Jankovsky, C., and Hawi, A., The "high solubility" definition of the current FDA guidance on biopharmaceutics classification system may be too strict for acidic drugs, Pharm. Res., 21, 293, 2004. 

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). 

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). 

It has recently been proposed that the Biopharmaceutical Classification System (BCS) can be used to predict intestinal drug disposition with regards to efflux transport and metabolism (339). Furthermore, on the basis of the key substrate BCS-related properties, permeability, and solubility, the system may be used to predict potential interactions mediated through changes in efflux and/or metabolism at the level of the intestine. 

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

This serves as an example of the extremes one can go if one tmly wants to better understand the process and the form of the compound in the product. This approach is less important for detecting polymorphic form conversion in the solid state, since polymorphic solubility typically varies by less than a factor of two and tablets at very low strength would generally be classified as a type one by the biopharmaceutical classification system. In addition, polymorphs rarely have pronounced differences in chemical stability. On the other hand, if a compound is somewhat unstable and significant amount of amorphous material is potentially present, this approach can be used to determine if it is responsible for drug instability in the tablet formulation. In any event, this reference serves as a very good example of the strength of a powerful approach that has not been widely applied in our industry. 

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.

Rinaki, E., Valsami, G., and Macheras, P., Quantitative biopharmaceutics classification system The central role of dose/solubility ratio, Pharmaceutical Research, Vol. 20, No. 12, 2003, pp. 1917-1925. 

In 1995, the Biopharmaceutics Classification System (BCS) was devised to classify drugs based on their aqueous solubility and intestinal permeability [1], According to the BCS, drug substances are classified as follows [2] ... 

Next to permeability, aqueous solubility is the most important biopharmaceutical property associated with oral drug absorption. These two properties have established the basis for a biopharmaceutical classification system (BCS) and have become the subject of an FDA guidance entitled Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a... 

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