Class II drugs: low solubility

One example of the application of response surface analysis is a study of critical formulation variables for 20 mg piroxicam capsules [100]. Piroxicam is a BCS Class II drug (low solubility and high permeability). This... 

Drugs in Class II have low aqueous solubility (but high membrane permeability), and any factor affecting dissolution rate would be expected to have an impact on the absorption of such compounds. Factors that are noted in Fig. 11, such as fluid pH, volume and viscosity, and bile secretion (especially in response to fatty foods), might be expected to play a role in dissolution rate and thereby affect absorption. Compounds that fall into this class include carbamazepine, cyclosporin, digoxin, griseofulvin, and spironolactone. Food would be expected to exert a potentially significant affect on... 

Class II drugs, i.e., low-solubility/high-permeability compounds, are expected to have a dissolution-limited absorption. Thus, for these types of drugs an IVIVC... 

Griseofulvin, a BCS class II drug (Fig. 2), is a well-known example whose poor aqueous solubility causes low and erratic oral bioavailability. As shown below, griseofulvin has a hydrophobic molecular structure, and is practically insoluble in water. Its oral absorption is highly variable, ranging from 25% to 100%, depending on the crystal size. Ultramicrosize griseofulvin preparations were shown to have 100% oral absorption (12). 

Biopharmaceutical classiLcation depends on both solubility and permeability of one drug. So, insoluble drugs with good permeability are clased as Class II drugs, and insoluble drugs with low... 

Drug A is a large, peptide-like molecule (MW 700 g/mol) and is highly lipophilic and poorly water soluble. It is a BCS Class II drugs. Its oral bioavailability in capsules and conventional tablet formulations is low, yielding practically undetected blood levels. A novel lipid formulation containing a solvent, a high HLB nonionic surfactant, and a fatty acid were developed with sufLcient oral bioavailability for use in the clinic. 

BCS Class II Low-solubility, high-permeability drugs. These drugs are the main scope of this chapter. In general, BCS Class II drug products are likely to be limited by the dissolution/solubility rate. 

Class II Drugs with low solubility and high permeability (e.g. Tacrolimus)... 

BCS Class II Low-solubility, high-permeability drugs. The bioavailability of products containing these compounds is likely to be dissolution-rate limited. For this reason, a correlation between in vivo bioavailability and in vitro dissolution rate (IVIVC) may be observed. 

A special case in dissolution-limited bioavailability occurs when the assumption of sink condition in vivo fails that is, the drug concentration in the intestine is dose to the saturation solubility. Class IV compounds, according to BCS, are most prone to this situation due to the combination of low solubility and low permeability, although the same could also happen for class II compounds, depending primarily on the ratio between dose and solubility. Non-sink conditions in vivo lead to less than proportional increases of bioavailability for increased doses. This is illustrated in Fig. 21.8, where the fraction of drug absorbed has been simulated by use of an compartmental absorption and intestinal transit model [35] for different doses and for different permeabilities of a low-solubility, aprotic compound. 

---