BCS Ⅱ
drugs are characterized by low
solubility and high
permeability. Improving their
solubility is considered an important approach to improve its oral
absorption. Recent
strategies to increase the
solubility of poorly-soluble
drugs may unexpectedly result in greatly depressed
permeability, ultimately leading to failure in improving oral
absorption. Based on the
mathematics of
membrane permeability coefficient of a
drug, the
membrane/aqueous partition coefficient is dependent on the
drug's
solubility in the gastrointestinal milieu, suggesting a unique interplay between the
solubility and
permeability of the
drug, and treating the one irrespectively of the other may be insufficient. When we focus on the increase of
drug solubility and overlook the
efficacy of
drug permeability, the positive effect of increased
solubility to
drug oral
absorption might be traded off by depressed
permeability. To provide rational formulary designs, by optimizing
excipients and evaluation, this
review summarizes
solubility-
permeability interplay for different types of solubilizing
techniques, such as
cyclodextrin,
surfactants-based vehicle, cosolvent, amorphous solid dispersions, other infectors such as P-gp transporters and new
techniques for simultaneous evaluation of
drug solubility and
permeability.