Читать книгу Biopharmaceutics - Группа авторов - Страница 72

Surfactants can improve the solubility of poorly soluble drugs. Surfactants are amphiphilic molecules that can form colloidal structures including micelles within an aqueous environment. Drug can then associate with these micelles, which improves the measured solubility. It is worth noting that the drug associated with micelles is not strictly dissolved but it is also no longer present as a solid. This distinction can be important for advanced modelling of drug solubilisation.

In biorelevant media, the bile salts and phospholipids form colloidal structures that include micelles that can enhance the measured solubility of the drug. Bile salt micelles will only form above the critical micelle concentration of the individual surfactant. Thus, small changes can have a large influence of the solubilisation capacity for a drug [13].

Studies have reported increased solubility of different drugs in FaSSIF compared to the same media without the bile salts [14]. This is shown in Figure 4.3.

Typically the solubility of drug in FaSSIF will be measured early in development as this can have implications for determining the most appropriate biopharmaceutics classification for the drug and to calculate the most relevant maximum absorbable dose.

Solubility increases are often also observed in FeSSIF compared to FaSSIF. However, the inherent variability associated with administration of drugs in the fed state makes reliance upon this solubility increase a risky strategy.

Figure 4.3 Comparison of the solubility of a series of drugs in blank FaSSIFf (left data point) and FaSSIF containing bile salts (right data point).

Source: Data from Fagerberg et al. [14].