PVC Bags Research Articles

Physico-chemical stability of docetaxel premix solution and docetaxel infusion solutions in PVC bags and polyolefine containers.

We assessed the physical and chemical stability of docetaxel infusion solutions. Stability of the antineoplastic drug was determined 1.) after reconstitution of the injection concentrate and 2.) after further dilution in two commonly used vehicle-solutions, 0.9% sodium chloride and 5% dextrose, in PVC bags and polyolefine containers. Chemical stability was measured by using a stability-indicating HPLC assay with ultraviolet detection. Physical stability was determined by visual inspection. The stability tests revealed that reconstituted docetaxel solutions (= premix solutions) are physico-chemically stable (at a level > or = 95% docetaxel) for a minimum of four weeks, independent of the storage temperature (refrigerated, room temperature). Diluted infusion solutions (docetaxel concentration 0.3 mg/ml and 0.9 mg/ml), with either vehicle-solution, proved physico-chemically stable (at a level > or = 95% docetaxel) for a minimum of four weeks, when prepared in polyolefine containers and stored at room temperature. However, diluted infusion solutions exhibited limited physical stability in PVC bags, because docetaxel precipitation occurred irregularly, though not before day 5 of storage. In addition, time-dependent DEHP-teaching from PVC infusion bags by docetaxel infusion solutions must be considered.

Decrease in the Concentration of Vitamin E in Blood and Tissues Caused by Di(2-Ethylhexyl) Phthalate, a Commonly Used Plasticizer in Blood Storage Bags and Medical Tubing

Background and Objectives: Significant amounts of di(2-ethylhexyl) phthlate (DEHP) leach into blood stored in DEHP-plasticized PVC bags. The aim of this study was to find out whether DEHP at these low levels has any effect on the concentration of vitamin E, an antioxidant which affords protection against free radical damage. Materials and Methods: DEHP was administered in low doses (150–750 μg/100 g body weight) to rats intraperitoneally and the concentration of vitamin E in the liver and testes was measured. Concentration of vitamin E was also measured in blood stored in glass bottles in the presence and absence of DEHP and in blood stored in DEHP-plasticized PVC bags. Results: A decrease in the concentration of vitamin E was observed in all cases. Administration of vitamin E to rats and incorporation of vitamin E in the additive solution in the case of blood prevented this decrease. Conclusion: DEHP even at very low doses caused a decrease in the concentration of vitamin E in liver and tests of rats given this substance. Blood stored in DEHP-plasticized bags also showed a decrease in the concentration of vitamin E.

Decrease in the Concentration of Vitamin E in Blood and Tissues Caused by Di(2‐Ethylhexyl) Phthalate, a Commonly Used Plasticizer in Blood Storage Bags and Medical Tubing

Significant amounts of di(2-ethylhexyl) phthlate (DEHP) leach into blood stored in DEHP-plasticized PVC bags. The aim of this study was to find out whether DEHP at these low levels has any effect on the concentration of vitamin E, an antioxidant which affords protection against free radical damage. DEHP was administered in low doses (150-750 microg/100 g body weight) to rats intraperitoneally and the concentration of vitamin E in the liver and testes was measured. Concentration of vitamin E was also measured in blood stored in glass bottles in the presence and absence of DEHP and in blood stored in DEHP-plasticized PVC bags. A decrease in the concentration of vitamin E was observed in all cases. Administration of vitamin E to rats and incorporation of vitamin E in the additive solution in the case of blood prevented this decrease. DEHP even at very low doses caused a decrease in the concentration of vitamin E in liver and tests of rats given this substance. Blood stored in DEHP-plasticized bags also showed a decrease in the concentration of vitamin E.

Distribution of stable isotopes in arid storms

Temporal distributions of the isotopic composition in arid rain storms and in the associated runoff were investigated in a small arid rocky basin in Israel. Customized rain and runoff samplers provided sequential water samples hermetically sealed in high-density PVC bags. In several storms where the runoff was isotopically depleted, compared with the rainfall, the difference could not be explained by fractionation effects occurring during overland flow. A water-balance study relating the runoff discharge to rainfall over a rocky watershed showed that the entire discharge is produced by a very small segment (1–2 mm) of the rain storm. The major objective, therefore, was to provide quantitative relations between segments of rainfall (rain showers and rain spells) and runoff. The time distribution of the composition of stable isotopes (oxygen and hydrogen) was used to quantify the correlation between the rain spell's amount and the consequent runoff. The aim of this work was to (a) utilize the dynamic variations in the isotopic composition in rainfall and runoff and model the magnitude of surface-storage capacity associated with runoff processes of overland flow, and (b) characterize the isotopic composition of the percolating water with respect to the isotopic distribution in rainfall and runoff events. The conceptual model postulates an isotopic mixing of overland flow with water within the depression storage. A transport model was then formulated in order to estimate the physical watershed parameters that control the development of overland flow from a certain rainfall period. Part I (this paper) presents the results and the assessment of the relative depression storage obtained from oxygen-18 and deuterium analyses that lead to the physical and mathematical formulation of a double-component model of kinematic-wave flow and transport, which is presented in Part II (accompanying paper).

Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl hydrazine in intravenous solutions stored in PVC bags by high performance liquid chromatography.

A high performance liquid chromatographic procedure is described for the determination of cyclohexanone leached in intravenous solutions from the poly(vinyl chloride) bags. After derivatization with 2,4-dinitrophenylhydrazine and extraction with pentane, the cyclohexanone derivative was analysed on a C18 BDS Hypersil column using mobile phase mixture of acetonitrile:water (55:45). Ultra-violet detection was performed at 368 nm. The limit of quantification was 30 ng/mL and the assay was linear from 0.05 to 50 micrograms/mL. The recovery was better than 95%. The proposed method is satisfactory in its accuracy and precision with particularly relative standard deviations (RSD) for intra-assay and inter-assay of below 10%. This method has been successfully used for the determination of cyclohexanone in aqueous solutions such as sodium chloride (0.9%) and glucose (5%) stored in PVC containers. The values obtained varied between 2.04 and 44.9 micrograms/mL according to solutions and volume.

Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl hydrazine in intravenous solutions stored in PVC bags by high performance liquid chromatography

Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl hydrazine in intravenous solutions stored in PVC bags by high performance liquid chromatography

Stability assessment of lyophilized intravenous immunoglobulin after reconstitution in glass containers and poly(vinyl chloride) bags.

Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2-3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care-giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico-chemical tests (molecularsize distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non-specific binding of complement (anti-complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 degrees C. The reconstituted product was also found to be stable at room temperature (25 degrees C) up to 12 h.

Stability of busulfan injection admixtures in 5 % dextrose injection and 0.9% sodium chloride injection

Objective. The purpose of this study was to deter mine the stability of busulfan injection at 0.5 and 0.1 mg/mL admixed in 5% dextrose injection and 0.9% sodium chloride injection in PVC and polyolefm bags over 24 hours at 23°C. Methods. The busulfan injection was prepared by dissolving the bulk powder in a 1:2 mixture of N,N-dimethylacetamide and polyethylene glycol 400 to form a 6 mg/mL solution. The injection was filtered and admixed in the infusion solutions to yield busulfan concentrations of 0.5 and 0.1 mg/mL. Evaluations were performed initially and after 4, 8, and 24 hours of storage for physical and chemical stability. The admix tures were evaluated for physical stability using visual observation in normal light and using a high-intensity monodirectional light beam as well as measuring turbidity. The chemical stability was evaluated by using a stability-indicating HPLC analytical technique. Results. No physical instabilities were observed. However, busulfan is chemically unstable. At 0.5 mg/mL, potency of at least 95% was retained through 4 hours and at least 90% was retained through 8 hours. After 24 hours, losses of 20% to 30% occurred. At 0.1 mg/mL, drug loss was more rapid. Potency of at least 90% was retained through 4 hours. Losses after 24 hours were about 30% to 40%. Conclusions. Busulfan injection admixed in 5% dextrose injection or 0.9% sodium chloride injection is unstable. At a concentration of 0.5 mg/mL, ade quate drug delivery is provided within 8 hours of admixture. At the lower concentration of 0.1 mg/mL, adequate drug delivery is only provided for 4 hours.

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 μg ml −1 for simulated infusion and to 250 and 1000 μg 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°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°C in the dark in PVC bags showed that it is highly unstable at 250 μg ml −1 in 0.9% NaCl injection and in 5% dextrose injection. On the other hand, under the same storage conditions, at 1000 μg 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 μg 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.

Long-term stability of 5-fluorouracil stored in PVC bags and in ambulatory pump reservoirs

Prolonged infusions of 5-fluorouracil (5FU) have been used since the early 1960s, but recently there has been a major resurgence of interest, partly because of the advent of electronically controlled portable infusion pumps. Admixtures of new formulation 5FU were subjected to stability studies to establish the feasability of continuous infusions. In the first study, the stability of 5FU, 1 or 10 mg ml −1, was determined in poly(vinyl chloride) (PVC) bags (0.9% sodium chloride injection or 5% dextrose injection) at 4 and 21°C after storage for 0, 1, 2, 3, 4, 7 and 14 days. In the second study, the stability of undiluted 5FU was tested at different temperatures (4 or 33°C) in ethylene vinyl acetate (EVA) or PVC ambulatory pump reservoirs after storage for 0, 3, 5, 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, colour change and pH. Evaporative water loss from the containers was measured. The stability of 5FU in PVC bags was unaffected by 14 days of storage at either 4 or 21°C. When stored in EVA reservoirs, 5FU was stable for at least 2 weeks at 33°C and for 3 days at 4°C (a precipitate was observed after 3 days). In PVC reservoirs, 5FU was stable for over 14 days at 33°C, but at 4°C a precipitate appeared after 5 days. Loss of water through the reservoirs was substantial only at 33°C for 14 days, and gave falsely high readings.

Leaching of diethylhexyl phthalate from PVC bags into intravenous teniposide solution

The stability of teniposide in various diluents and polyvinyl chloride bags was determined, and the extent of leaching of di(2-ethylhexyl) phthalate (DEHP) from PVC bags caused by the teniposide formulation was measured. No significant drug loss was observed during simulated infusions ( n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% Nacl). To minimize patient exposure to DEHP, teniposide solutions may be stored in a glass or polyolefin container and delivered through polyethylene-lined i.v. administration sets. If PVC bags are used for preparing teniposide solutions, the injections must be used immediately after preparation or stored 4–5 h at + 4°C.

Compatibility study of methotrexate with PVC bags after repackaging into two types of infusion admixtures

The stability and compatibility of methotrexate in admixtures for continuous intravenous infusion using PVC bags and administration set were studied. Methotrexate was reconstituted and diluted to 4.5 mg/ml for infusion in PVC containers, and to 0.225 and 24 mg/ml for storage in PVC bags containing 5% dextrose or 0.9% sodium chloride injections. Admixtures were stored at + 4/dgC and with protection from light for 30 days. Analyses were performed by HPLC. In every case, no significant drug loss was observed during storage or simulated infusions using PVC infusion bags and administration sets.

Stability and compatibility of cisplatin and carboplatin with PVC infusion bags.

The availability and compatibility of drugs from solutions infused via PVC infusion bags through PVC administration sets have been examined. No significant drug loss was observed during simulated infusions using PVC infusion bags and administration sets over time periods used in hospitals (cisplatin, 2 h; carboplatin, 1 h). The stability of carboplatin was studied in 5% dextrose. In 0.9% NaCl, we observed that carboplatin could be converted to cisplatin in the presence of chloride ions. With cisplatin, no significant difference was found between infusion solutions (5% dextrose or 0.9% NaCl). The stability of cisplatin (5% dextrose or 0.9% NaCl) and carboplatin (5% dextrose) was also studied in PVC bags after storage in the dark at room temperature. The results show that the drugs were stable over the 9-day storage period studied.

Platelets Stored for 6 Days in a Polyolefin Container in a Synthetic Medium with Minimal Plasma Carry-Over

Platelet concentrates (PC) were stored for 6 days in either polyolefin (PO) or polyvinylchloride/di-(2-ethylhexyl)phtalate (PVC/DEHP) bags in 100% plasma or in a synthetic medium with 35 or 10% plasma. For all conditions studied the usual in vitro parameters were well maintained, with a pFI above 6.8. In both bag types platelets can be satisfactorily stored for 6 days in a synthetic medium with minimal amounts of residual plasma. For this medium, the PO bag offers a slight advantage with respect to the preservation of platelet ATP content (>80 versus >70% in the PVC bags) and aggregation and adhesion capacity. The adhesion capacity increased in the PO bags, while it decreased in the PVC bags.

Interactions physicochimiques et mode de conservation du Diprivan ®

Only few publications consider physio-chemical interactions and stability of propofol. On the basis of current experience, this agent is safe for use in polypropylene or polypropylene/polystyrene syringes, diluted 1 in 5 in 5% dextrose if necessary. The potential hazards are as follows: 1. Propofol may undergo oxidation when not stored under nitrogen, or when in contact with oxidizing agents (active ingredients or excipients of other preparations). 2. The emulsion may be destabilised by contact with mineral or organic cations (calcium, magnesium, dibasic amino acids etc.) or acids (citric acid etc.). 3. Losses of propofol may occur by adsorption-diffusion (surface adherence combined with penetration of plastic material) during storage in PVC bags or during administration by means of PVC infusion sets. Most of these hazards have still to be evaluated under controlled conditions.

Stability and compatibility studies of cephamandole nafate with PVC infusion bags

A rapid isocratic technique was developed for the analysis of cephamandole nafate and cephamandole in parenteral solutions using high-performance liquid chromatography (HPLC) with UV detection and C 18 column. The availability and compatibility of drugs from solutions infused via plastic infusion bags through plastic administration sets have been examined. No significant drugs loss was observed during simulated infusions ( n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl). The stability of drugs was also studied in solution in PVC bags after storage at room temperature and at 4°C without protection from light. The results show the stability of cephamandole nafate during 24 h at room temperature and 7 days storage at 4°C to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). However, an almost immediate and total transformation of cephamandole nafate to cephamandole in 5% glucose has been observed, whereas in 0.9% NaCl both forms were found in similar proportions.

Compatibility of diazepam (Valium®), clorazepate dipotassium salt (Tranxene®) and midazolam hydrochloride (Hypnovel®) with Stedim 6®, a new multilayer polyethylene-lined film for infusion bags: a comparative study with polyvinyl chloride bags

The compatibilities of diazepam, clorazepate dipotassium salt and midazolam hydrochloride with Stedim 6® bags have been studied and compared with those observed with PVC bags. Stedim 6 is a new polyethylene-lined material, composed of several layers, one of which is more air-impermeable. Whereas the losses of diazepam in PVC bags reached 25 and 28% after 72 h storage in 5% dextrose and 09% sodium chloride solutions, respectively, the extent of sorption in Stedim 6 bags did not exceed 10%. Clorazepate dipotassium salt and midazolam hydrochloride compatibilities with Stedim 6 were excellent and slightly better than with PVC, given that no loss was observed in 5% dextrose and in 09% sodium chloride solutions. The compatibility of midazolam hydrochloride in neutral admixtures was far better with Stedim 6 (18% loss after 72 h) than with PVC (66% loss). Multilayer containers appear to be a convenient solution for the storage of lipophilic drug infusion admixtures.

The influence of storage time on the nucleotide concentration of canine platelets.

Nucleotide concentrations of canine platelets during storage for 50 days were determined to find out the variation in the concentration of various nucleotides in canine platelets during storage at +4 degrees C for 50 days. Platelets of 3 dogs were stored in whole blood in PVC bags containing CPDA-1 stabilizer. The bags were kept at 4 degrees C for 50 days. Changes in the energy metabolism of the platelets during storage were determined by successive measurements of the following nucleotides: adenosine-diphosphate (ADP), adenosine-tri-phosphate (ATP) and guanosine-tri-phosphate (GTP). In preparation for the measurement of their nucleotide content, the platelets were isolated from the blood at regular intervals and their membranes destroyed by deep freezing, thawing, double sonification in ice and protein precipitation with perchloric acid. The concentration of nucleotides within the platelets was determined by "High Pressure Liquid Chromatography" (HPLC). ADP, ATP and GTP were identified in the peak areas of the HPLC using 3 different techniques: comparison of retention time of standard nucleotide solutions as control samples, enzyme tests and thin layer chromatography. Adenosine-mono-phosphate (AMP), adenosine, hypoxanthine and inosine mono 5'-phosphate (IMP) were not found in dog platelets. Platelet ATP concentration decreased significantly during 50 days of storage (p < 0.001), and was reduced to 24% of the concentration measured after 1 hour of storage on day 50. ADP concentration also dropped significantly during 50 days of storage (p < 0.001). On day 50 the average ADP concentration was reduced to about 34% of the concentration measured after 1 hour of storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability and compatibility studies of pefloxacin, ofloxacin and ciprofloxacin with PVC infusion bags

A rapid isocratic technique was developed for the analysis of fluoroquinolones (pefloxacin, ofloxacin and ciprofloxacin) in parenteral solutions using high-performance liquid chromatography (HPLC) with fluorimetric detection and a C 18 column. The availability and compatibility of drugs from solutions infused via plastic infusion bags through plastic administration sets have been examined. No significant drug loss was observed during simulated infusions ( n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl). The stability of drugs was also studied in solution in PVC bags after storage at room temperature without protection from light. The results show the stability of pefloxacin and ciprofloxacin during 6 h of storage to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). However, we have observed more significant variations with ofloxacin in the solution of 5% glucose, but remaining below 10%.

Identification of caprolactam as a potential contaminant in parenteral solutions stored in overwrapped PVC bags.

Semipreparative liquid chromatographic separation and subsequent off-line mass spectrometry have revealed caprolactam as a new contaminant in intravenous solutions. The content of the lactam was found to be 1.2-15.0 mg l-1 determined by liquid chromatography. Contamination is attributed to migration of caprolactam from the protecting plastic envelope through the PVC barrier and into the intravenous solution. Migration occurs during the final heat sterilization process.