Effect of elevated temperature and light on the stability of butorphanol tartrate.

The purpose of this investigation was to determine the short-term stability of butorphanol tartrate in presence of diluents. A 10-mg/mL solution of butorphanol tartrate was diluted to 5 mg/mL using normal saline, 5% dextrose in water (D5W), or sterile water for injection. The diluted solutions were divided into two groups. The effect of temperature was tested by placing one group of sealed amber vials at room temperature and at 37 degrees C. The effect of light was studied by placing a second group in amber and clear vials, then exposing them directly to light. At regular time intervals over a period of 5 weeks, the solutions were analyzed for butorphanol tartrate and degradation products using a high-performance liquid chromatography assay. The concentration of butorphanol tartrate remained practically unchanged, indicating that butorphanol tartrate is not affected by heat or light in the presence of any of the diluents over a period of 5 weeks.

Short-term stability of atenolol in oral liquid formulations.

The objective of this study was to determine the stability of atenolol in extemporaneously compounded liquid formulations. Two sets of formulations were prepared using either pure atenolol powder or atenolol tablets. Vehicles used for preparation were simple syrup, a methylcellulose-based vehicle, Ora-Sweet, Ora-Plus, and Ora-Sweet SF. The concentration of atenolol in the formulations was 2 mg/mL. Samples were collected at regular time intervals over a period of three months, and atenolol concentration was determined using a stability-indicating, high-performance liquid chromatography (HPLC) assay. All formulations were also visually observed for signs of settling. The HPLC results showed that all formulations prepared using the methylcellulose-based vehicle and Ora-Sweet SF were stable (ie, greater than 90% of atenolol remained unchanged) for more than 28 days. On the other hand, formulations prepared with simple syrup and Ora-Sweet were stable only for 14 days. Formulations prepared using simple syrup and Ora-Sweet as vehicles were also placed at elevated temperatures in order to study the effect of temperature on the stability of atenolol. The concentration of atenolol that remained unchanged depended on the vehicle used and the temperature at which the formulations were stored.

Influence of cholestyramine resin administration on single dose sulindac pharmacokinetics.

Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine cholestyramine effect on the plasma concentrations of sulindac and its sulfide metabolite following concurrent and staggered (sulindac 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. Subjects received 400 mg sulindac orally followed by serial blood sampling for sulindac and sulindac sulfide plasma concentrations over a 24-hour period. During the concurrent phase, 4 g of cholestyramine was coadministered resulting in a decrease (p < 0.05) in the area under the curve (AUC) for sulindac compared to sulindac alone (7.11 +/- 3.25 micrograms-h/ml vs 31.65 +/- 7.94 micrograms-h/ml respectively). Also, the sulindac sulfide AUC decreased (p < 0.05) to 7.26 +/- 4.37 micrograms-h/ml coadministration of both drugs compared to 44.69 +/- 11.81 micrograms-h/ml when sulindac is given alone. When the same doses of each drug were given 3 hours apart, the AUC for sulindac (17.88 +/- 3.69 micrograms-h/ml) and its sulfide metabolite (20.12 +/- 7.46 micrograms-h/ml) were still significantly decreased (p < 0.05) when compared to sulindac given alone (31.65 +/- 7.94 micrograms-h/ml for sulindac and 44.69 +/- 11.81 micrograms-h/ml for sulindac sulfide). Based on the lower AUCs for sulindac and sulindac sulfide, separating sulindac and cholestyramine by 3-hour intervals did not prevent the interaction. It is likely that the enterohepatic recycling features of sulindac may not prevent the interaction with cholestyramine even when the 2 drugs are staggered.