UNUSUAL DISSOLUTION BEHAVIOR OF CEFPODOXIME PROXETIL - EFFECT OF PH AND IONIC FACTORS

Cefpodoxime proxetil [CPDX-PR(A+B)] possesses one asymmetric carbon at om in the eater group and exists as a mixture of two diastereoisoners, the S-isomer [CPDX-PR(A)] and the R-isomer [CPDXPR(B)]. The dissoluti on behaviour of each CPDX-PR from a constant surface area was studied to obtain the intrinsic dissolution rare constant. A linear relationsh ip existed in all cases when the total amount released was plotted aga inst the square root of time. The slopes of the lines thus obtained we re regarded as apparent intrinsic dissolution rate constants. The appa rent intrinsic dissolution rate constants of CPDX-PR(A) increased with decreasing pH, but those of CPDX-PRs (B) and (A+B) exhibit maxima at pH 1.6. Under more acidic conditions, a thick, wet surface layer consi sting of the gel of crystalline CPDX-PR(B) salt was formed to restrict the dissolution of CPDX-PRs. We also investigated the effect of ions such as acid species, ionic strength and salt species on the dissoluti on behaviour of CPDX-PR(A+B). In pH 1.2 aqueous solutions prepared wit h sulfuric acid or nitric acid instead of hydrochloride, even thicker wet surface layers were formed to deep-ease the apparent intrinsic dis solution rate constants of CPDX-PR(A+B). Ionic strength facilitated ge l formation in restricting the dissolution of CPDX-PRs. There were lit tle differences in the apparent intrinsic dissolution rate constant an d the extent of gel formation when cation species were changed while k eeping ionic strength constant. In contrast the apparent intrinsic dis solution rate constants and the content of the surface layer were grea tly affected by anion species. CPDX-PR(B) is confirmed to react with t hese anion species to form salts in the gelatinized state.