Formulation biopharmaceutical classification

Use of Nonactive Pharmaceutical Excipients in Oral Drug Formulations Biopharmaceutical Classification System Considerations... 

When formulating with crystalline drugs that have received a Biopharmaceutical classification system (BCS) ranking as being either... 

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

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. 

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. 

Improved bioavailability. More than 40% of the NCEs (new chemical entity) discovered have good membrane permeability but poor aqueous solubility (i.e.. Biopharmaceutics Classification System II). By formulating the NCE in solution inside a Softgel (e.g., lipid based) or in micro/nano emulsion, the solubility and hence the bioavailability of the compound may be improved. ... 

Wilding, I.R. Evolution of the biopharmaceutics classification system (bcs) to oral modified release (mr) formulations what do we need to consider Eur. J. Pharm. Sci. 1999, 8, 157-159. 

Ideally such a formulation should be universally applicable. This was achieved by the invention of the drug nanocrystals. " With the nanocrystals one went one step beyond micronization in fact to "nanonization". Drug nanocrystals dissolve very fast and thus they can overcome oral bioavailability problems in which the dissolution velocity is the rate limiting step for absorption (e.g. drugs of class II of the Biopharmaceutical Classification System (BCS)). Meanwhile five products for oral administration are on the market. Because of their small size drug nanocrystals can also be injected intravenously. With a size below 1 fim, typically between 200-600 nm, they are much smaller than the smallest blood capillaries being in the range of 5-6 tm. Intravenous products are under development. 

The biopharmaceutical classification system (BCS) was first introduced in 1995 to facilitate the drug development, and it is based on two independent variables that influence bioavailability, viz., aqueous solubility and intestinal permeability (Amidon et al. 1995 FDA 2000). Compounds that belong to BCS class II or IV are of primary interests from a formulation perspective and, therefore, solubility enhancement using formulation intervention is the key driver for improving the bioavailability of poorly soluble drugs. From a conceptual perspective, the dissolution rate can be expressed by the following equation (Noyes and Whitney 1897) ... 

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