Class II drugs: low solubility high permeability

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... 

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. 

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... 

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 Low solubility, high permeability (i.e. lipophilic drugs)... 

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

The BCS classes are defined as follows Class I. High Solubility (S) - High Pe Class II. Low S - High Peff Class III. High S - Low P( (T Class IV. Low S - Low Per(. A drug is considered as highly permeable when the extent of absorption is complete in humans, defined by the US FDA as being more than 90%, whereas EMEA requires... 

There are abundant examples in the literature that demonstrate the direct relationship between dissolution rate and bioavailability. One such example is that of piroxicam (Figure 7.6), a potent non-steroidal anti-inflammatory drug that was launched in 1981 by Pfizer for multiple conditions such as arthritis (osteoarthritis and rheumatoid arthritis) and spondylitis. It is a zwitterionic drug (p ai = 1S6 and p a2 = 5.46) and is classified as a low solubility and high permeability drug (i.e., class II) based on the Biopharmaceutics Classification System (BCS). In an attempt to improve its bioavailability after oral administration, the authors prepared three different ethanolamine salt forms i.e., mono-, di- and triethanolamine salts). These salt forms were selected based on prior literature precedence where they enhanced the percutaneous absorption of piroxicam.PK studies of the ethanolamine salts revealed that both the exposure (AUC) and the C ax of piroxicam in plasma followed the same trend as the dissolution profile at pH 6.8, which varied in the order mono- > di- > tri-piroxicam. The monoethanolamine salt showed the highest exposure with the relative bioavailability increasing almost 1.9-fold, while the di- and tri- salts were 1.7 times better than piroxicam. The C ax values showed 2.14-, 1.6- and... 

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