Dissolution rates of doxycycline free base and hydrochloride salts.

The dissolution rates of doxycycline monohydrate, hyclate, and hydrochloride dihydrate crystal forms were investigated using the static pellet method. Solubility product equilibria with chloride ion strongly suppressed the dissolution rate of the hydrochloride dihydrate salt. This form dissolved about fourfold slower in 0.1 N HCl than in water, which was consistent with its solubility in these media. Specificity for chloride was demonstrated by the rapid dissolution rate for the hydrochloride dihydrate in 0.1 N methanesulfonic acid. The dissolution rates of the hyclate, a solvated hydrochloride salt, and the free base were not sensitive to chloride ion. The results show that common ion equilibria with chloride can strongly reduce the dissolution rate of a thermodynamically stable hydrochloride salt form, while the free base or a metastable hydrochloride salt are not similarly affected.