Physicochemical stability of etoposide diluted at range concentrations between 0.38 and 1.75 mg/mL in polyolefin bags.

Introduction: According to the manufacturers, the diluted solution of etoposide should not exceed 0.4 mg/mL because precipitation may occur. For high doses or for patients requiring fluid restrictions, etoposide phosphate may be an option but shortages occurs frequently. The objective of this work was to study the stability of etoposide solutions between 0.38 and 1.75 mg/mL, diluted in 0.9% sodium chloride (0.9% NaCl) or 5% glucose (G5%) in polyolefin bags, stored at 25°C and between 2°C to 8°C, in a 61-day period. This study also observed the impact of an infusion pump on the physical and chemical stability of etoposide solutions. Materials and method: Chemical stability was analysed at days 0, 9, 16, 21, 28 and 61 by high-performance liquid chromatography. Physical stability was evaluated by visual and subvisual inspection. The action of an infusion pump on solutions was evaluated to verify the impact of the mechanical pumping action on the etoposide solutions. This investigation was performed at day 61, at the end of the study. Results: Etoposide solutions diluted at 0.38, 0.74 and 1.26 mg/mL in G5% and stored at 25°C were stable for 61 days and at 1.75 mg/mL for 28 days. In 0.9% NaCl, etoposide was less stable, with more precipitations observed. The action of an infusion pump has not caused any physical modifications. Conclusion: Storage at 25°C and G5% as diluent are recommended for etoposide high concentration with 61-day stability up to a concentration of 1.26 mg/mL and 28-day stability up to a concentration of 1.75 mg/mL. As a precaution, the use of an administration set with an in-line micro-filter is nevertheless recommended. Storage at 2°C to 8°C and the use of 0.9% NaCl increase the risk of precipitation.

Stability of alemtuzumab solutions at room temperature.

PURPOSE: The 24-hour stability of alemtuzumab solutions prepared at concentrations not included in the product label and stored in glass or polyolefin containers at room temperature was evaluated. METHODS: Triplicate solutions of alemtuzumab (6.67, 40, and 120 µg/mL) in 0.9% sodium chloride were prepared in either glass bottles or polyolefin containers and stored at room temperature under normal fluorescent lighting conditions. The solutions were analyzed by a validated stability-indicating high-performance liquid chromatography (HPLC) assay at time zero and 8, 14, and 24 hours after preparation; solution pH values were measured and the containers visually inspected at all time points. Stability was defined as the retention of ≥90% of the initial alemtuzumab concentration. RESULTS: HPLC analysis indicated that the percentage of the initial alemtuzumab concentration retained was >90% for all solutions evaluated, with no significant changes over the study period. The most dilute alemtuzumab solution (6.67 µg/mL) showed some degradation (91% of the initial concentration retained at hour 24), whereas the retained concentration was >99% for all other preparations throughout the study period. Solution pH values varied by drug concentration but did not change significantly over 24 hours. No evidence of particle formation was detected in any solution by visual inspection at any time during the study. CONCLUSION: Solutions of alemtuzumab 6.67 µg/mL stored in glass bottles and solutions of 40 and 120 µg/mL stored in polyolefin containers were stable for at least 24 hours at room temperature.

A rapid liquid chromatography-tandem mass spectrometry analysis of whole blood sirolimus using turbulent flow technology for online extraction.

BACKGROUND: Sirolimus is an immunosuppressant used in solid organ transplantation. Due to variable individual pharmacokinetics and narrow therapeutic ranges, therapeutic drug monitoring (TDM) is critical to the success of post-transplantation patient care. We developed a rapid method quantifying whole blood sirolimus using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with an automated online extraction technology. METHODS: Whole blood (100 microL) was mixed with a precipitation solution containing internal standard (32-desmethoxyrapamycin) and centrifuged at 15,634 x g for 10 min. The supernatant (50 microL) was injected onto a turbulent flow preparatory column and then a C18 analytical column. The mass spectrometer was set for positive electrospray to monitor the ammonium adducts. RESULTS: Analytical time was 4 min/injection. Inter- and intra-assay variation coefficients across three concentration levels ranged from 2.3% to 7.4%. The method was linear from 1.0 to 100.0 ng/mL with an accuracy of 93.3%-100.0%. No carryover was detected from samples at 313.6 ng/mL. There was no obvious ion suppression from patient samples or interference from other commonly used immunosuppressants. Good correlation with an in-house commercial LC-MS was observed. CONCLUSIONS: The LC-MS/MS method coupled with turbulent flow technology is rapid and efficient in TDM of whole blood sirolimus.

Odour investigation of granular polyolefins for flexible food packaging using a sensory panel and an electronic nose.

A study was carried out of the odour properties of polyolefins destined for flexible food packaging. A total of 25 homo- and copolymers of ethylene and five homo- and copolymers of polypropylene in pellet grade were analysed by a sensory panel. Principal component analyses of sensory data showed a perceptible and quantifiable difference between samples. Generally, polypropylene materials were judged less odorous than the majority of polyethylene pellets, especially the ethylene vinyl acetate copolymers. The feasibility of using a commercial electronic nose, equipped with 10 metal oxide semiconductors, to discriminate between the odour of plastic materials was also explored. Instrumental results were satisfactory and correlated well with panel answers, as shown by partial least-squares regression. Furthermore, application of a cluster analysis made it possible to differentiate polymer odours into strong, medium and weak.

[Influence of sterilization treatments on continuous carbon-fiber reinforced polyolefin composite].

OBJECTIVE: To evaluate the influence of sterilization treatment on continuous carbon-fiber reinforced polyolefin composite (CFRP) so as to provide experimental reference for selection of sterilization method for CFRP. METHODS: Seventy bars of CFRP were divided into 7 equal groups to undergo sterilization by autoclave, 2% glutaraldehyde soaking, 75% alcohol soaking, ethylene oxide sterilization, and Co-60 gamma ray irradiation of the dosages 11 kGy, 25 kGy, and 18 kGy respectively, and another 10 bars were used as blank controls. Then the bars underwent three-point bending test and longitudinal compression test so as to measure the biomechanical changes after sterilization treatment, including the maximum load, ultimate strength, and elastic modulus. RESULTS: Three-point bending test showed that the levels of maximum load of the all experimental groups were lower than that of the control group, however, only those of the 3 Co-60 irradiation groups were significantly lower than that of the control group and that Co-60 radiation lowered the level of maximum load dose-dependently; and that the levels of ultimate strength of all the all experimental groups were lower than that of the control group, however, only those of the 3 Co-60 groups were significantly lower than that of the control group and that the higher the dosage of Co-60 radiation the lower the level of ultimate strength, however, not dose-dependently. The elastic modulus of the Co-60 25 KGy group was significantly higher than that of the control group, and there was no significant difference in the level of ultimate strength among the other groups. Longitudinal compression test showed that the levels of maximum load and ultimate strength of the 3 Co-60 irradiation groups, autoclave group, and circular ethylene groups were significantly lower than that of the control group, and there was no significant difference in elastic modulus among different groups. CONCLUSION: During sterilized package of CFRP products produced in quantity autoclave sterilization and Co-60 gamma ray irradiation sterilization should be avoided. Ethylene oxide is proposed as the best sterilization method. If gamma ray irradiation is to be used further technology improvement is necessary.

[Permeability to phi chi 174 bacteriophages in polyolephin membrane condoms]. / Determinación de la permeabilidad viral de los condones de membrana de poliolefina al bacteriófago phi chi 174.

Membranes used for the manufacture of condoms eventually can develop tiny pores, thereby decreasing dramatically their effectiveness as a physical barrier against the transmission of infectious agents. A technique was designed that was based on the ability of bacteriophage viruses to trespass membranes and to infect certain bacteria species, and then developing lysis plaques in the colonies of the host bacteria. The effectiveness of 60 polyolefin condoms in preventing the diffusion of the bacteriophage phi chi 174(ATCC13706-B1), 27 nm diameter, was compared to 20 latex condoms. Physiological conditions such as pressure, pH, superficial tension, length, time of exposure and viral titre were simulated. A pressurization system was designed, in which compressed air was injected simultaneously to ten condoms. Four of the 60 polyolefin condoms and one of the 20 latex condoms were permeable to the virus. Therefore, at least 93% of the condoms evaluated were able to contain the virus. The difference in permeability between the two types of membranes was not statistically significant (P = 0.79).

Skin adhesives and skin adhesion. 1. Transdermal drug delivery systems.

The use of pressure-sensitive adhesives (PSAs) for skin-contact applications is discussed. The requirements of such adhesives in various applications are examined in detail. Commercially available classes of PSAs used for skin-contact applications are the acrylics, the polyisobutylenes, and the silicones. The main application examined in this review is transdermal drug delivery. The roles played by the PSA in two types of transdermal designs are described. Correlations between in vivo and ex vivo measurements of adhesion are discussed. Also, the reported human studies of various commercially available transdermals are examined critically, with a view to assessing the relative performance capabilities of each type of transdermal design. Finally, a comprehensive listing of currently commercialized transdermals is given.

A new, non-toxic, curing agent for synthetic polyolefins.

The purpose of this study was to investigate benzocyclobutene (BCB) derivatives as non-toxic curing agents to replace accelerated sulfur systems in certain synthetic biomedical materials. Prototype artificial spinal discs have been made and implanted in a few patients from a carbon black-filled copolymer of 1-hexene and 5-methyl-1,4-hexadiene (MHD), which is sulfur cured. The polymers investigated in this study were composed of 1-hexene, allyl-BCB, and MHD (or 7-methyl-1,6-octadiene, MOD). Curing was effected through reactions on BCB, forming carbon-carbon crosslinks. Preliminary cytotoxicity tests showed the material to be non-toxic, and the physical and mechanical properties of the BCB-cured materials were comparable with those of the sulfur-cured polymers.

[Study of components of standard samples of polyene macrolide antibiotics by the methods of high performance liquid chromatography and SIEAP mass spectrometry]. / Izuchenie komponentnogo sostava standartnykh obraztsov polienovykh makrolidnykh antibiotikov metodom vysokoéffektivnoi zhidkostnoi khromatografii i mass-spektrometrii ERIAD.

The component composition of reference samples of polyenic macrolide antibiotics such as nystatin, mycoheptin, amphotericin B and levorin was studied by HPLC and chromatographic mass spectrometry in comparison to the WHO standards. It was shown that the samples were close by their component composition to the analogous samples of the WHO standards.

Urostomy appliances and stoma care routines. The relation to peristomal skin complications.

The aim of the study was to describe types of appliances and stoma care routines and evaluate their relation to peristomal skin complications. Sixty-six patients with a cutaneous uretero-ileostomy were interviewed and the peristomal skin was assessed according to Classification of Peristomal Skin (CPS). The results show a conservatism regarding the types of appliance and the stoma care routines. More than half of the patients used the same product at follow-up as they were initially fitted with three to 14 years earlier. The routines adopted by the patients were often inadequate, resulting in skin complications. Continuous exposure of the skin to urine by creation of a too wide opening in the face-plate and infrequent changing of the appliance resulted in development of pseudoverrucose skin lesions.

Changes in insulation of wetsuits during repetitive exposure to pressure.

This investigation was intended to a) establish a relationship between pressure and thickness (and hence insulation) of wetsuits during acute changes in pressure from 0.5 to 5 atmospheres absolute (ATA); b) determine the effect of repetitive compression-decompression (C-D) procedures on the insulation properties of wetsuits; and c) assess the possible recovery of insulation after cessation of repetitive C-D. Various wetsuits with different thicknesses and types of linings were selected. In all wetsuits, insulation and thickness were both reduced as similar, curvilinear functions of acutely increasing pressure in the range of 0.5-5.0 ATA. Effects of repetitive C-D (3 ATA) were studied in 5-mm-thick suit samples with various linings. The insulation of suits (0.100-0.120 degrees C.W-1.m-2) rapidly decreased after the first 5000 C-D. In suits without linings (skin suits), the insulation was reduced to 0.080 degrees C.W-1.m-2 at 5000 C-D and revealed no further reduction during the continuation of C-D cycles up to 30,000. Suits lined with single- or double-sided jersey showed a continuous decrease in the insulation and thickness as the number of cycles increased up to 12,000 and remained at a lowered value (0.060 degrees C.W-1.m-2) until the termination of C-D (30,000 times). A nearly complete recovery of thickness was seen 10 days after cessation of C-D treatment in the skin suit when C-D cycles were less than 3500; however, no recovery was observed in suits with linings (either single- or double-sided) in 25 days.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of antioxidants and complexons on the stability of the microbiological standard for mycoheptin]. / Izuchenie vliianiia antioksidantov i kompleksonov na stabil'nost' mikrobiologicheskogo standarta mikogeptina.

Stability is one of the most important indices of the quality of antibiotic microbiological standards. At present the expiry date of the mycoheptin standard (a specially purified preparation) is 1 year when stored in sealed ampoules in an inert gas at a temperature of -20 degrees C. To prolong the expiry date of the standard the effect of various antiohidants and complexons on its stability was studied with the method of "accelerated aging". Sodium hexametaphosphate and Trilon B were tested as complexing agents and propyl gallate, ionol, N-phenyl-2-napththyl amine, mannitol and their mixtures were tested as antioxidants. The substances were applied in an amount of 3 per cent of the antibiotic weight. The favourable effect of the complexons on mycoheptin stability was shown. Their stabilizing effect was potentiated by addition of certain antioxidants.

[Study of the possibility of stabilizing a levorin microbiological standard]. / Izuchenie vozmozhnosti stabilizatsii mikrobiologicheskogo standarta levorina.

The effect of a number of factors, providing increased stability of the levorin microbiological standard was studied. It was shown that air-tight packing and inert gas atmosphere (antibiotic storage in ampoules sealed under nitrogen) significantly increased the antibiotic stability. It was also shown that hydrochinone had the highest positive effect on levorin stability.