Effect of preparation method and storage on rifampin concentration in suspensions

To determine the effect of four preparation methods and extended storage on rifampin concentration in extemporaneously prepared suspensions.

Four preparation methods were used: mixing intravenous (i.v.) rifampin in syrup (A); manufacturer's recommended technique of mixing capsule (Rifadin) contents in syrup (B); triturating capsule contents in syrup into a paste and adding remaining syrup while mixing (C); and triturating capsule contents in syrup into a paste, adding syrup, retriturating the slurry, and adding remaining syrup while mixing (D). Samples were drawn from each of five bottles of each of the four preparations stored at 4 degrees C, immediately after mixing (day 0), and on days 7, 14, 28, 42, 56, 70, and 91 days during storage. Rifampin was measured by a stability-indicating HPLC method.

The measured mean concentrations of rifampin were nearly 100 percent of the initial concentration in the suspension prepared from i.v. rifampin solution (method A) during the first 56 days of storage. In contrast, the measured concentrations were substantially lower than expected in the suspensions prepared by methods B, C, and D. The mean rifampin concentrations in suspensions prepared by methods B, C, and D were only 14.5, 38.6, and 68 percent, respectively, of the initial concentration achieved by method A. The rifampin concentrations increased with storage time in suspensions prepared by methods B, C, and D. The mean rifampin concentration was lower than 90 percent during the first 14 days with methods B and C, and the first 7 days with method D. The highest mean concentrations were observed on day 42 with method B, and on day 28 with methods C and D. All methods yielded 90% of the labeled potency (10 mg/mL) on day 56.

Our results showed that preparation method can influence the dispersion, and thus the measured concentration, of rifampin in aliquots of suspensions prepared from capsules and stored in plastic bottles. Suspensions prepared from capsules led to lower-than-expected rifampin concentrations; those prepared from i.v. rifampin did not. Rifampin was stable in each type of suspension for 56 days at 4 degrees C.