Pharmaceutical Manufacturing Handbook: Production and

is evident form the fact [51] that the majority of the marketed drugs are highly
soluble ( > 55% in classes I and III). Sometimes, enhancing the permeability by altering
the drug ’ s chemical structure may be counterproductive. This because of the
associated increase in molecular weight that attenuates the permeability enhancement
gained with structural modifi cation. On the other hand, optimization of drug
solubility may be more fruitful if the poor permeability is overcome by increasing
drug solubility to provide a high drug concentration at the absorption site. However,
this may be a diffi cult strategy if the dose is very high. The preformulation team
should use the “ appropriate tools ” at every stage of the drug discovery and development
process to guide or alert other development teams about drug solubility and
permeability issues (Figure 17 ).
6.2.4
Solubility/permeability
Maximum absorbable dose
BCS classification
Ora ldosage form
development
FIGURE 17 Flow chart for determining absorption potential of a drug during drug discovery
and development. Solubility and permeability studies from preclinical phase are used to
calculate the maximum absorbable dose and, when correlated to BCS, this can provide information
on its biopharmaceutics class. This is useful to estimate if the drug absorption would
be dissolution and/or permeability limited for developing appropriate drug delivery
strategies.
STABILITY CHARACTERISTICS
STABILITY CHARACTERISTICS 965
Early drug discovery
Exploratory studies
Drug development
Clinical development
Drug stability is an essential component of preformulation testing. Establishing
the stability of the drug under a variety of conditions is an expensive and time -
consuming process. It cannot be overemphasized that the availability of a stability -
indicating assay is the key to stability studies. The preformulation scientist works
closely with the analytical method development team in developing a stability -
indicating assay. During the early stages, a foolproof stability - indicating assay may