Studies of the abnormal bioavailability of clarithromycin capsules and relative in vitro quality control

To verify the formulation of clarithromycin capsules through bioavailabilit y testing in healthy volunteers and to study the in vitro parameters for qu ality control, the bioavailability of clarithromycin capsules was tested in a two-way, randomised single-close, cross-over study conducted with ten he althy male volunteers with reference tablets. The plasma samples were measu red by microbiological assay of antibiotics with Bacillus pumilus [CMCC(B)6 3202]. The dissolution and disintegration characteristics of clarithromycin capsules were comparatively studied in media, the pH of which reflected th e in vivo gastric pH range. The difference in solubility-pH profile and spe ctrophotographical response between clarithromycin and its degradation prod ucts was investigated The relative bioavailability of clarithromycin capsul es is 78.73 +/- 23.19% compared with tablets. The dissolution of clarithrom ycin capsules complied well with the official standards in the officially s lated medium (acetate buffer), but was obviously pH-dependent in HCl soluti ons ar a pH of 1 to 5, with slow release at pH 1 or greater than or equal t o 4. The disintegration profile showed no pH-dependence. The solubility-pH profile revealed similar characteristics to the dissolution-pH profile. The UV-vis responses of clarithromycin degradation products at 482 nm were 10- 128 less than those of clarithromycin base. The low bioavailability of clar ithromycin was doe to pH-dissolution dependence. The dissolution media, qua ntification method and the solubility of clarithromycin might be key factor s for the in vitro control of the bioavailability of clarithromycin capsule s.