Class IV drugs: low solubility

Fasted conditions were simulated using water for gastric dissolution and FaSSIF for small intestinal dissolution. The difference between the observed plasma profile and the in vitro dissolution profile, only showed a satisfactory correlation for sanfetrinem however, the superiority of FaSSIF to compendial media was not evident, most probably due to the relatively high solubility of this drug. For atovaquone, the correlation was better for the biorelevant model than the compendial model, but still not acceptable. GV150013X may be a class IV drug (low solubility—low permeability) and this might explain that an IVIVC was not possible. 

Class IV drugs have low aqueous solubility and poor membrane permeability and as such are often considered as poor drug candidates for oral administration. Other routes of administration may need to be considered. For example, neomycin falls into this category, and its oral use is to achieve sterilization of the gut. There is too little information about these compounds and the effect of food to offer general observations. 

Class IV Drugs with low solubility and low permeability (e.g. Paclitaxel)... 

BCS Class IV Low-solubility, low-permeability drugs. These compounds have very poor oral bioavailability. They are not only difficult to dissolve but often exhibit limited permeability across the GI mucosa. These drugs tend to be very difficult to formulate and can exhibit very large intersubject and intrasubject variability. 

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. 

BCS Class IV Low-solubility, low-permeability drugs. These drugs are characterized by very poor oral bioavailability and tend to exhibit very large inter- and intrasubject variability. Hence, unless the dose is very low, they are generally poor oral drug candidates [1],... 

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... 

Class IV Low solubility, low permeability (i.e. hydro-phobic drugs)... 

---