Cocrystals Mitigate Negative Effects of High pH on Solubility and Dissolution of a Basic Drug.

ABSTRACT: Weakly basic drugs are predisposed to order of magnitude decreases in solubility and dissolution as pH increases from 1 to 7 along the gastrointestinal tract. Such behavior is known to be detrimental to drug absorption. The work presented here shows how cocrystals of basic drugs with acidic coformers can mitigate these negative effects. Cocrystals of ketoconazole (KTZ) with adipic, fumaric, and succinic acids exhibit a parabolic solubility dependence on pH such that with increasing pH, solubility decreases, reaches a minimum, and increases. Cocrystals exhibit pH_max values between 3.6 and 3.8, above which they generate supersaturation with respect to drug. Cocrystal supersaturation index (SA), defined as S_cocrystal/S_drug, changes from 1 (pH_max) to

SUBMITTER: Chen YM 

PROVIDER: S-EPMC6261521 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature