Soluble classification

An outline of the solubility classification procedure is given in Table X 1,5,2, whilst the characteristic features of each of the solubility groups are summarised in Table XI,5,3. 

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

Fligge, T.A. and Schuler, A. 2006. Integration of a rapid automated solubility classification into early validation of hits obtained by high throughput screening. J. Pharm. Biomed. Anal. 42 449. 

It has been argued [224] that the use of a single solubility value in the original BCS article [153], Figure 6.15, for solubility classification is inadequate since... 

Precipitation leads to light scattering which is detected. Following solubility classifications are used poor soluble (< 10 mg/ml) medium solubility (10-100 mg/ml) and good solubility (> 100 mg/ml). 

Table 4 The United States Pharmacopeia Solubility Classification...

Solvent solubility is widely used to classify coal-derived products (1.,2). The most popular methods are based on some form of Soxhlet extraction. Methods involving Soxhlet extraction are normally time consuming thus complete solvent solubility classification is laborious. An alternate method, used initially by Bertolacini et al. (3.) and modified for our use, employs pressure filtration. Pressure filtrations carried out at room temperature have been used to classify a number of coal-derived products obtained under a variety of liquefaction conditions. 

The method requires a compound in the low milligrams and works best for very insoluble compounds, which also are the most difficult to quantitate by other methods. The method is relatively slow, since for best results the titration rate is greatly slowed as the precipitation point is reached. The compound is solubilized at the beginning of the assay, either by pH dissolution of solid or by dissolution of a concentrated DMSO stock solution in aqueous media of appropriate pH. As a result there is no control as to which polymorphic form of the compound corresponds to the solubility product. The method is likely to be particularly useful in the solubility classification of compounds according to the FDA bioavailability waiver system because of the extensive validation of the method, its reproducibility, and its particular applicabifity to compounds with the poorest solubility. 

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