Effects of PVC bags sterilization process on the 5-fluorouracil stability.

The stability and compatibility of 5-fluorouracil (5-FU) in undiluted or diluted admixtures stored in beta-radiation sterilized portable poly(vinyl chloride) (PVC) infusion bags were investigated. Admixtures containing 5-FU 50 mg ml(-1) not diluted or 25 mg ml(-1) diluted in 0.9% sodium chloride injection were placed in 100 or 250 ml empty PVC reservoirs sterilized initially by beta-irradiation. They were protected from light and placed at 37 degrees C. Two ml quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 5, 6, 7 and 14 days. For each condition, samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change and pH. Evaporative water loss from the containers was also measured. 5-FU was compatible with PVC containers in all tested conditions for 14 days. No loss of drug and no color change were detected throughout the storage period. pH values were stable and neither precipitation nor loss of water through the reservoirs was observed when drug 50 or 25 mg ml(-1) (diluted using 0.9% sodium chloride) was stored in 100 ml capacity polyvinyl PVC bags. However, when stored in 250 ml capacity PVC bags, the 5-FU solution showed precipitation after 13 and 14 days of storage, but no drug loss was detected due to a substantial loss of water. The precipitation of the drug was due to the decrease of pH induced by the dehydrochlorination of PVC during beta-irradiation leading to the formation of hydrochloric acid in solution. Differences observed between 100 and 250 ml capacity bags can be explained by the greater area of PVC present in 250 ml reservoirs, and consequently more HCl formed. Finally, more plasticizer, di-(2-ethylhexyl) phthalate (DEHP), was then detected in drug solutions stored in 250 ml PVC bags. So, we recommend the use of 100 ml bags to store 5-FU at longer storage times and higher temperatures.

Compatibility study of 5-fluorouracil with PVC bags after repackaging into two types of infusion admixtures.

The stability and compatibility of 5-fluorouracil (5-FU) in admixtures for continuous intravenous infusion using PVC bags and administration sets were studied. 5-fluorouracil was reconstituted and diluted to 1.8 mg/ml for infusion in polyvinyl chloride and glass containers, and to 1 mg/ml to 16 mg/ml for storage in polyvinyl chloride bags containing 5 per cent dextrose or 0.9 per cent sodium chloride injections. Admixtures were stored at +4 degrees C and with protection from light, for 7 days. Analyses were performed by HPLC. No significant drug loss was observed during simulated infusions using PVC infusion bags and administration sets vs glass bottles and administration sets, over an infusion period used in hospitals (24 h). The solution stored at +4 degrees C with protection from light in PVC bags showed that at 1 mg/ml to 16 mg/ml, 5-fluorouracil was stable at least for 7 days in 0.9 per cent sodium chloride and 5 per cent dextrose.

Stability study of fotemustine in PVC infusion bags and sets under various conditions using a stability-indicating high-performance liquid chromatographic assay.

The stability and compatibility of fotemustine, a nitrosourea anticancer agent, in 5% dextrose solution with polyvinyl chloride (PVC) containers and administration sets were studied under different conditions of temperature and light. The drug was diluted to 0.8 and 2 mg ml(-1) in 100 or 250 ml 5% dextrose injection solutions for 1-h simulated infusions using PVC bags and administration sets with protection from light. After preparation in the PVC bags containing 5% dextrose, fotemustine was also prepared at the same concentrations and stored at 4 degrees C for 48 h and at room temperature (22 degrees C) or at sunray exposure ( > 30 degrees C) over 8 h with or without protection from light. The solution samples were removed immediately at various time points of simulated infusions and storage, and stored at -20 degrees C until analysis. The physical compatibility with PVC and chemical stability in solution of fotemustine were assessed by visual examination and by measuring the concentration of the drug in duplicate using a stability-indicating high-performance chromatographic assay. When admixed with a 5% dextrose solution, fotemustine 2 and 0.8 mg ml(-1) was compatible and stable over 1-h of simulated infusion using PVC bags through PVC administration sets with protection from light. On the other hand, in the same diluent, fotemustine was compatible and stable with PVC bags for at least 8 h at 22 degrees C with protection from light and for at least 48 h at 4 degrees C with protection from light. There were no pH variation, no visual change, no color change, no visible precipitation and no loss of the drug. Conversely, when the solutions were exposed to light (ambient or solar), the drug concentration decreased rapidly, leading to the production of a degradation product as shown by mass spectral analysis and a discoloration of the solutions. Finally, in all cases, no DEHP (di-2-ethylhexyl phthalate) was detected in the injection solution.

Stability and compatibility studies of zorubicin in intravenous fluids and PVC infusion bags.

The stability of zorubicin (ZOR) in admixtures for continuous intravenous infusion was studied. ZOR was reconstituted and diluted to 600 micrograms ml-1 for simulated infusion and to 250 and 1000 micrograms ml-1 for storage in poly(vinyl chloride) (PVC) bags containing 5% dextrose injection or 0.9% sodium chloride injection (0.9% NaCl). Bags were then stored at refrigerated temperature (4 degrees C) and in the dark for 24 h. ZOR concentrations in each admixture were tested by stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet detection. No substantial loss of ZOR was observed during simulated infusions (n = 4) using PVC infusion bags and administration sets over a 1 h infusion. The drug stored at 4 degrees C in the dark in PVC bags showed that it is highly unstable at 250 micrograms ml-1 in 0.9% NaCl injection and in 5% dextrose injection. On the other hand, under the same storage conditions, at 1000 micrograms ml-1, ZOR is more stable in 0.9% NaCl injection (6 h) than in 5% dextrose (4 h). The reported superior stability of the 1000 micrograms ml-1 in 0.9% NaCl can be explained, at least in part, by the difference in pH. Changes in pH, particularly a decrease, seem to affect adversely the stability of ZOR. In fact, ZOR is rapidly converted into daunorubicin, the dominant degradation product, which is more cardiotoxic than the parent drug. Therefore, several precautions must be observed when the commercial product (Rubidazone) is prepared and reconstituted in i.v. fluids and containers.

Stability and compatibility of four anthracyclines: doxorubicin, epirubicin, daunorubicin and pirarubicin with PVC infusion bags.

A rapid isocratic technique was developed for the analysis of four anthracyclines (doxorubicin, epirubicin, daunorubicin and pirarubicin) in parenteral solutions using high pressure liquid chromatography (HPLC) with fluorescence detection and a C18 Hypersil ODS column. The availability and compatibility of these drugs from solutions infused via PVC infusion bags through PVC administration sets have been examined. No significant drug loss was observed during simulated infusions (n = 4) for 24 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl), except for pirarubicin. The reconstitution of pirarubicin in 0.9% NaCl was impossible, because we observed a precipitation of the compound in solution. The stability of the drugs was also studied in solution, in PVC bags after storage at 4 degrees C with protection from light. The results show the stability of doxorubicin, epirubicin and daunorubicin during 7 days of storage to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). In the case of pirarubicin, the stability of the drug was satisfactory during 5 days of storage in 5% glucose, but beyond, we observed a degradation of the compound with formation of doxorubicin in the infusion solution.