Sterile Water For Injection Research Articles

Pre-treatment with probiotics prolongs survival after experimental infection by multidrug-resistant Pseudomonas aeruginosa in rodents: An effect on sepsis-induced immunosuppression

Based on several randomised clinical studies indicating benefit from oral probiotic intake for the prevention of hospital-acquired infections in critically ill patients, this study aimed to explain the mechanism of action of probiotics for the prevention of lethal experimental infection by multidrug-resistant (MDR) Pseudomonas aeruginosa. Experiments using an Escherichia coli strain susceptible to all antimicrobials were also conducted. C57BL/6 mice were pre-treated intraperitoneally with sterile water for injection or Lactobacillus plantarum. Survival was recorded and mice were sacrificed for measurement of apoptosis and tissue bacterial overgrowth and for isolation and culture of splenocytes for cytokine production. Experiments were repeated after pre-treatment with a commercial preparation of four probiotics (L. plantarum, Lactobacillus acidophilus, Saccharomyces boulardii and Bifidobacterium lactis; LactoLevure®). Peripheral blood mononuclear cells (PBMCs) of healthy volunteers were stimulated by heat-killed P. aeruginosa following pre-treatment with medium or probiotics. Pre-treatment with L. plantarum significantly prolonged survival after challenge by either MDR P. aeruginosa (66.7% vs. 31.3%; P=0.026) or E. coli (56.0% vs. 12.0%, P=0.003). Survival benefit was even more pronounced when mice were pre-treated with LactoLevure®. Tissue bacterial outgrowth and apoptosis of white blood cells and splenocytes were not altered. TNFα and IL-10 production by splenocytes of mice pre-treated with probiotic was increased and IFNγ production was decreased. Pre-treatment with LactoLevure® restored production of IL-17. Stimulation of human PBMCs after probiotic pre-treatment was accompanied by reduced gene expression of SOCS3. The results suggest that the protective effect of probiotics is mediated through prevention of sepsis-induced immunosuppression.

The Efficacy of Voriconazole Eye Drops Reconstituted in Sterile Water for Injection

Purpose: To investigate the efficacy of voriconazole 1% eye drops reconstituted in sterile water for injection and stored in the fridge or room conditions and correlate the results to bibliographic data. Methods: Voriconazole powder was reconstituted with water for injection, in order to prepare a 1% solution. The solution was separated in sterile vials stored in the fridge or in the cupboard. Malt extract agar solutions were prepared with the addition of this voriconazole solution to achieve concentrations of 1 μg/ml, 2 μg/ml and 4 μg/ml and the same procedure was repeated after one and after two weeks. Petri plates were inoculated with standardized solutions of Candida albicans, Aspergillus fumigatus, Alternaria alternata, Fusarium solani and Fusarium oxysporum. The fungal growth was compared to the control plates, which contained only malt extract agar without voriconazole. Results: The voriconazole solutions remained effective for more than two weeks (18 days), independently of the storage conditions. The concentration of 1μg/ml was effective against Candida albicans and Aspergillus fumigatus, the 2 μg/ml against Alternaria alternata (and until the 17th day also against Fusarium oxysporum but not on the 18th day) and the 4 μg/ml against Fusarium oxysporum but not against Fusarium solani. Conclusion: The reconstituted with sterile water for injection voriconazole eye drops are effective against various fungi. Fusarium solani was resistant up to the concentration of 4 μg/ml. The susceptibility of the examined fungi varies and thus, considerations should be raised about the combination with other routes of administration in order to achieve the appropriate drug concentrations in the eye. There was no significant difference in the effectiveness of voriconazole solutions in relation to the storage conditions.

Formulation and stability study of a pediatric 2% phenylephrine hydrochloride eye drop solution

We present formulation and stability evaluation of a 2% (w/v) phenylephrine hydrochloride biocompatible eye drop solution, routinely prepared in hospital pharmacy under aseptic conditions, for retinal examination of neonates and premature infants. Eye drop solution was formulated by dissolution of phenylephrine hydrochloride and disodium hydrogen phosphate as buffering agent in sterile water for injection and sodium chloride for injection as isotonic agent. The previous solution was sterile filtered through under aseptic conditions, in an iso class 5 air quality clean room under horizontal laminar airflow hood. Physical stability (visual inspection, osmolality measurements), chemical stability (pH measurement, phenylephrine assay by liquid chromatography coupled with an ultra-high resolution and accurate mass) and sterility evaluation of phenylephrine eye drop solution stored at ambient temperature were studied during 60 days. The formulated eye drop solution had a pH of 6.90±0.05 and an osmolality of 285±2 mOsm/kg. Throughout the 60 days study the solutions remained clear without any precipitation or color modification, sterility was maintained, pH and osmolality were not significantly modified and no significant loss of product was detected using liquid chromatography coupled with an ultra-high resolution and accurate mass instrument suggesting the lack of degradation. These results indicate that 2% phenylephrine hydrochloride eye drop solutions were physically, chemically and microbiologically stable for at least 60 days when stored in type I amber glass vials at room temperature, allowing the compounding of higher batch sizes.

Dalbavancin: First I.V. antibiotic for acute bacterial skin infections

Dalbavancin: First I.V. antibiotic for acute bacterial skin infections

Catridecacog: First drug to treat rare genetic blood clotting disorder

Catridecacog, or coagulation factor XIII A-subunit, recombinant (Tretten—Novo Nordisk), a minimally invasive option for treating rare congenital factor XIII A-subunit deficiency, has received FDA approval. According to Novo Nordisk, catridecacog helps to prevent bleeding in children and adults who have the coagulation factor XIII A-subunit deficiency, an extremely rare genetic disorder. Catridecacog is the first drug to receive FDA approval for this indication. FDA also granted catridecacog orphan drug status because it treats a rare disease. Factor XIII is a terminal enzyme in the blood coagulation cascade that stimulates cross-linking of fibrin and other proteins in the fibrin clot to promote hemostasis. In human plasma, factor XIII circulates as a heterotetramer of two functional subunit proteins—two factor XIII A-subunits and two factor XIII B-subunits. The factor XIII A-subunit acts as the enzyme, while factor XIII B-subunit acts as a carrier for the factor XIII A-subunit. During coagulation, the factor XIII is activated by thrombin and calcium; the factor XIII A-subunit dissociates from the factor XIII B-subunit to become active and help cross-link fibrin to enhance platelet and clot adhesion to injured tissue. Patients with the factor XIII A-subunit deficiency have a significantly lower level of the active subunit, thus resulting in less stable clotting for injured tissue. Catridecacog binds to the free human factor XIII B-subunit, as factor XIII A-subunit, to strengthen fibrin clots, impede fibinolysis, and enhance platelet adhesion to the injury site. Give patients the Médication Guide and review it with them carefully. Verify the diagnosis, since catridecacog should not be used for prophylactic treatment of bleeding in patients with congenital factor XIII B-subunit deficiency. Advise patients that breakthrough bleeding may be a sign and symptom of inhibitor formation, and they may have to see their health care provider to measure antibody concentrations. Tell patients to inform their health care provider of all the medications they may be taking. Patients with the factor XIII A-subunit deficiency have a significantly lower level of the active subunit, thus resulting in less stable clotting for injured tissue. During clinical development, researchers studied the effectiveness of catridecacog in 77 patients with coagulation factor XIII A-subunit deficiency. Catridecacog was effective in preventing bleeding in 90% of the patients when given the recommended dose of 35 IU/ kg. The mean age of study participants was approximately 26 years (63.4% > 18 years), and the male to female ratio was 3:2. The most common related adverse events (occurring in >1% of patients treated with catridecacog) were headache, pain in the extremities, injection site pain, and an increase in nonneutralizing antibodies. Use of catridecacog is contraindicated in patients who have known hypersensitivity to the active substance or to any of the excipients. Because increased levels of rFXIII may increase the risk of thrombosis, health professionals should exercise caution in patients with a predisposition to conditions of thrombosis. Incorrect storage of the product after reconstitution may result in loss of sterility and increased levels of activated rFXIII. Catridecacog, coagulation factor XIII A-subunit, recombinant (Tretten)Manufacturer: Novo NordiskDrug class: Blood coagulation factorsIndication: Treatment of congenital factor XIII A-subunit deficiencyDosage: 35 IU/kg once monthly■To administer, reconstitute with sterile water for injection with a 10-mL syringe.■A dose recommendation cannot be made for older adults, pregnant patients, or children younger than age 6 years due to lack of data.Of note: Treatment should be initiated under the supervision of a physician experienced in the treatment of rare bleeding disorders. Do not use vial if solid matter and discoloration are present in the reconstituted product. Administer at a rate not exceeding 1–2 mL per minute. Do not administer as a drip or with other infusion solutions. Manufacturer: Novo Nordisk Drug class: Blood coagulation factors Indication: Treatment of congenital factor XIII A-subunit deficiency Dosage: 35 IU/kg once monthly■To administer, reconstitute with sterile water for injection with a 10-mL syringe.■A dose recommendation cannot be made for older adults, pregnant patients, or children younger than age 6 years due to lack of data. Of note: Treatment should be initiated under the supervision of a physician experienced in the treatment of rare bleeding disorders. Do not use vial if solid matter and discoloration are present in the reconstituted product. Administer at a rate not exceeding 1–2 mL per minute. Do not administer as a drip or with other infusion solutions.

Comparision of uroprotective activity of reduced glutathione with Mesna in Ifosfamide induced hemorrhagic cystitis in rats

Background:Ifosfamide (IFO) is widely used DNA-alkylating agents in cancer chemotherapy for management of solid tumors and hematological malignancies. However, hemorrhagic cystitis limits the use of IFO.Objectives:To compare the efficiency of reduced glutathione with 2-Mesna in reducing Ifosfamide (IFO) induced hemorrhagic cystitis (HC) in wistar rats.Materials and Methods:Ifosfamide and 2-Mesna were dissolved in sterile water for injection and administered to wistar rats of albino strains. The rats were randomly assigned to one of the four groups of 6 rats each: Group I: Vehicle control; Group II: 120 mg/kg of IFO alone by intraperitoneal injection (i.p); Group III: 40 mg/kg Mesna i.p., at the same time and at 4 and 8 h after IFO administration; Group IV: 500 mg/kg of glutathione i.p., 30 min prior to IFO as above. The animals were observed for 5 days. On 6th day, rats were sacrificed by dissecting the intrajugular vein. The bladders were macroscopically and histopathologically evaluated.Results:Control animals had normal bladders with assigned scores of ‘0’ for the three parameters of edema, hemorrhage and histopathological changes. All the animals receiving IFO (group II) had evidence of HC as evidenced by alterations of edema and hemorrhages. These alterations were almost abolished (P < 0.001) by the glutathione (group III) or Mesna (group IV) in IFO-treated animals.Conclusion:Glutathione could be as useful as Mesna in the preventive management of IFO-induced HC.

Formulation, development and evaluation of injectable formulation of Aspirin

The objective of this study was to develop and manufacture a stable parenteral formulation for Aspirin, a non steroidal anti-inflammatory agent. The solubility and stability of the drug was determined. Solubility studies suggested that Aspirin exhibited poor aqueous solubility but showed appreciable solubility in non-aqueous solvents. Based on the preformulation studies, a lyophilized parenteral formulation containing 25 mg/mL of Aspirin was prepared in a solvent system containing of 80% v/v water and 20% v/v polyethylene glycol-400 (PEG-400). Rubber closures, filter membranes, and liquid transfer tubing were selected on the basis of compatibility studies. The formulation was subjected to accelerated stability studies. After reconstitution with sterile water for injection, Aspirin injection was stable for a period of 8 hr at 2°C to 8°C. Accelerated stability studies suggested that the lyophilized product should be kept at controlled room temperature for longterm storage. The proposed non-aqueous solvent concentration used, are known to safe hence, toxicities/safety related issues may not raise. The proposed techniques would be economical, convenient and safe. Thus, the study opens the chances of preparing lyophilized formulation of poorly-water soluble drugs.

Abstract 683: Toxicity of aerosolized azacytidine (Vidaza) in mice.

Abstract Background: Azacytidine, a prototypical demethylation agent, has been approved to treat myelodysplastic syndrome. Commercial azacytidine (Vidaza) is delivered to patients by subcutaneous or intravenous administration. In a previous study, we found that aerosolized azacytidine can 1) inhibit human orthotopic lung cancers in a mouse xenograft model, 2) demethylate several promoters of tumor suppressor genes reported to be hypermethylated in human lung cancer, and 3) be better tolerated and more effective than systemic administration. These studies specifically addressed toxicity associated with aerosolized delivery of Vidaza to the lungs; specifically hematologic and pulmonary toxicity. Methods: Vidaza was dissolved into sterile water for injection and aerosolized in a clinical standard aerosol system. Swiss mice male and female 6/group were restricted into a nose-only exposure system for receiving the aerosol. We treated the mice at 2 different doses, 7.5 mg/m2 daily x 7 days and 2.5 mg/m2 daily x 7 days. Blood, sternum (for bone marrow), and lung were collected at 3 and 6 weeks after the final aerosol treatment. The bone and lung were fixed in 10% neutral buffered formalin and routinely processed to paraffin blocks, sectioned, stained, and evaluated histologically. In a preliminary pharmacokinetic study, azacytidine concentrations in the blood and lung samples from mice receiving 2.5 mg/m2 of aerosolized azacytidine were determined by a MS-HPLC method previously described by others. Results: Neither dose of aerosolized Vidaza resulted in bone marrow changes. A mild pneumonitis was present in lungs from mice treated with 7.5 mg/m2 at 3 weeks but was not evident at six weeks (reversible). No pulmonary toxicity was observed at the 2.5 mg/m2 dose. The preliminary pharmacokinetic study data indicate very low drug concentrations in the blood and much higher concentrations in the lungs. Conclusion: Our study demonstrates that low dose aerosolized azacytidine can be safely administered to mice. Reversible pulmonary toxicity (pneumonitis) was observed at 7.5 mg/m2 at 3 weeks post treatment. The recommended starting dose of aerosolized azacytidine in human clinical phase I trial should be 2.5 mg/m2. Supported by NIH grant 5R01CA154755 to Roman Perez-Soler and Yiyu Zou. Citation Format: Xuan Qiu, Rani Sellers, Yuanxin Liang, Bilal Piperdi, Roman Perez-Soler, Yiyu Zou. Toxicity of aerosolized azacytidine (Vidaza) in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 683. doi:10.1158/1538-7445.AM2013-683

A randomized comparative study between selective walking spinal anesthesia and general anesthesia for anorectal surgeries in outpatient settings

BackgroundSpinal anesthesia is gradually increasing in ambulatory setting. The limiting factor to the more widespread use of spinal anesthesia in the outpatient setting refers to the effect of residual block. Selective spinal anesthesia (SSA) with low dose lidocaine was compared with modern general anesthesia (GA) technique in day care anorectal surgeries.ObjectiveOur objectives in this study was to compare SSA with propofol and fentanyl based modern GA as regard to 1 – operating conditions 2 – patients’ and surgeon’s satisfaction, 3 – intraoperative, postoperative adverse events and 4 – recovery profiles in ambulatory anorectal surgeries.MethodsProspective randomized clinical study was conducted on 60 patients undergoing elective day case anorectal surgery. The patients were randomly allocated into one of two groups (GA and SSA groups) of 30 patients each. In GA group anesthesia was induced with intravenous fentanyl (2 μg/kg) and propofol (2–3 mg/kg). Airway was secured with I-gel supraglottic airway. Anesthesia was maintained by sevoflurane 1.5–2%, nitrous oxide 60% in oxygen mixture. SSA group patients received spinal anesthesia with lidocaine 20 mg and fentanyl 25 μg to a total volume of 3 ml with sterile water for injection. Intraoperative, postoperative and home adverse events, time to ambulate, time to home discharge, patients’ and surgeon’s satisfactions were statistically compared between both groups.ResultsBoth anesthetic techniques showed acceptable operating conditions and high rate of patients’ satisfaction. Low pain intensity, shorter time to ambulate and home discharge in SSA compared to GA with a p value < 0.001. Intraoperative hemodynamic stability was reported in both groups. No major postoperative or home adverse events in both groups.ConclusionsSSA with low dose lidocaine may be suitable alternative and competitive for modern GA in ambulatory anorectal surgery.

Physical compatibility of various drugs with neonatal total parenteral nutrient solution during simulated Y-site administration

The physical compatibility of various drugs with neonatal total parenteral nutrient (TPN) solution during simulated Y-site administration was evaluated. Study drugs were selected based on the lack of compatibility data with them and neonatal TPN solution and the frequency of use in a local neonatal unit. These drugs included amiodarone, caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, midazolam, pentobarbital, phenobarbital, and rifampin. Equal volumes of neonatal TPN solution or sterile water for injection were combined with study drugs or sterile water for injection at concentrations used clinically in neonates. Each test was performed in triplicate. The samples were examined via turbidimetric analysis and visually against light and dark backgrounds immediately after mixing and at 0.25, 0.5, 1, 2, and 3 hours after mixing. Analysis of variance was used to determine statistically significant differences between the test and control solutions. Many of the drugs studied exhibited no visual or turbidimetric evidence of incompatibility when combined with neonatal TPN solution for up to three hours in a simulated Y-site injection. Pentobarbital, phenobarbital, and rifampin formed visible precipitation immediately after mixing with the neonatal TPN solution. Caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, and midazolam exhibited no visual or turbidimetric evidence of incompatibility when combined with a neonatal TPN solution for up to three hours in a simulated Y-site injection. Amiodarone, pentobarbital, phenobarbital, and rifampin were not compatible with the neonatal TPN solution and should not be coadministered via Y-site injection.

Validating a faster method for reconstitution of Crotalidae Polyvalent Immune Fab (ovine)

BackgroundReconstitution of CroFab® (Crotalidae Polyvalent Immune Fab [ovine]) lyophilized drug product was previously performed using 10 mL sterile water for injection followed by up to 36 min of gentle swirling of the vial. CroFab has been clinically demonstrated to be most effective when administered within 6 h of snake envenomation, and improved clinical outcomes are correlated with quicker timing of administration. An alternate reconstitution method was devised, using 18 mL 0.9% saline with manual inversion, with the goal of shortening reconstitution time while maintaining a high quality, efficacious product. MethodsAn analytical study was designed to compare the physicochemical properties of 3 separate batches of CroFab when reconstituted using the standard procedure (10 mL WFI with gentle swirling) and a modified rapid procedure using 18 mL 0.9% saline and manual inversion. The physical and chemical characteristics of the same 3 batches were assessed using various analytic methodologies associated with routine quality control release testing. In addition further analytical methodologies were applied in order to elucidate possible structural changes that may be induced by the changed reconstitution procedure. ResultsBatches A, B, and C required mean reconstitution times of 25 min 51 s using the label method and 3 min 07 s (a 88.0% mean decrease) using the modified method. Physicochemical characteristics (color and clarity, pH, purity, protein content, potency) were found to be highly comparable. Characterization assays (dynamic light scattering, analytical ultracentrifugation, LC–MS, SDS-PAGE and circular dichroism spectroscopy were also all found to be comparable between methods. DiscussionWhen comparing CroFab batches that were reconstituted using the labeled and modified methods, the physicochemical and biological (potency) characteristics of CroFab were not significantly changed when challenged by the various standard analytical methodologies applied in routine quality control analysis. Additionally, no changes in the CroFab molecule regarding degradation, aggregation, purity, structure, or mass were observed. ConclusionThe analyses performed validated the use of the more rapid reconstitution method using 18 mL 0.9% saline in order to allow a significantly reduced time to administration of CroFab to patients in need.

Y-site compatibility of vancomycin and piperacillin/tazobactam at commonly utilized pediatric concentrations.

Vancomycin and piperacillin/tazobactam are common empiric antibiotics in hospitalized pediatric patients. Studies evaluating intravenous (IV) compatibility at various concentrations show inconsistent results. The objective of this study was to determine the Y-site compatibility of vancomycin 10 mg/mL and piperacillin/tazobactam 112.5 mg/mL. Vancomycin (10 g vial) was reconstituted using sterile water for injection (SWFI) and diluted with 5% dextrose in water (D5W) to a final concentration of 10 mg/mL in an evacuated IV bag. Piperacillin/tazobactam (40.5 g vial) was reconstituted and diluted with SWFI to a final concentration of 112.5 mg/mL (100 mg/mL piperacillin) in an evacuated IV bag. Both antibacterial stock solutions were then stored in a refrigerator at 4°C (39.2°F). Initial solution appearances, including color, clarity, and particulates, were documented. Diluted solutions were mixed in a quantity of 3 mL of each vancomycin and piperacillin/tazobactam in glass test tubes. Subsequent evaluation included pH assessment and visual evaluation with unaided eye, magnifying glass, high-beam light, and via Spec-20 turbidimeter. Solution mixtures were evaluated upon mixing and again at 30 minutes, 1 hour, and 4 hours after mixing. Initial combination of vancomycin and piperacillin/tazobactam resulted in a milky precipitate, visible to the unaided eye, which dissipated 15 seconds after mixing. No precipitate was visualized via any method at any additional time point. Turbidimetry and pH readings did not demonstrate differences from baseline measurements. A combination of vancomycin 10 mg/mL and piperacillin/tazobactam 112.5 mg/mL demonstrated precipitation immediately upon mixing. Co-infusion of vancomycin and piperacillin/tazobactam via Y-site should be considered incompatible.

Approaches for airway humidity in patients undergoing tracheal resection due to inhalation injury

Objective To explore effective humidity therapies for patients undergoing tracheal resection due to inhalation injury.Methods 36 patients undergoing tracheal resection due to inhalation injury were randomly divided into study group and control group.The study group received continuous intratracheal drip of sterilized water for injection and the speed of dripping was adjusted according to the viscosity of the aspired sputum.The control group received conventional therapy with intratracheal drip of 0.9％ sodium chloride solution of 2 to 4ml for airway humidity every 2 hours.Viscosity of sputum,efficacy of sputum aspiration,and incidence of airway complications were compared between the two groups.Results In the study group,the rate of grade Ⅲ viscosity was 5.6％,the frequency of daily sputum aspiration was (17.72 ± 1.57)times,and the positive rate of sputum culture was 11.1％; while in the control group,the rate of grade Ⅲ viscosity was 55.6％,the frequency of daily sputum aspiration was (20.61 ± 1.26)times,and the positive rate of sputum culture was 50％.Dilution of sputum,efficacy of sputum aspiration,and incidence of airway complications differed significantly between the two groups (P ＜ 0.05).Conclusions For patients undergoing tracheal resection due to inhalation injury,continuous intratracheal drip of sterilized water for injection with a proper speed of dripping is superior to regular intratracheal drip of 0.9％ sodium chloride solution.The previous approach can effectively dilute sputum,humify airway,and reduce the frequency of sputum aspiration and the airway complications. Key words: Inhalation injury; Tracheal resection; Airway humidity

Stability of azacitidine in sterile water for injection.

The product monograph for azacitidine states that once reconstituted, the drug may be held for only 30 min at room temperature or 8 h at 4°C. Standard doses result in wastage of a portion of each vial, and the cost of this wastage is significant, adding about $156 000 to annual drug expenditures at the authors' institution. To evaluate the stability of azacitidine after reconstitution. Vials of azacitidine were reconstituted with sterile water for injection. At the time of reconstitution, the temperature of the diluent was 4°C for samples to be stored at 4°C or -20°C and room temperature for samples to be stored at 23°C. Solutions of azacitidine (10 or 25 mg/mL) were stored in polypropylene syringes and glass vials at room temperature (23°C), 4°C, or -20°C. The concentration of azacitidine was determined by a validated, stability-indicating liquid chromatographic method in serial samples over 9.6 h at room temperature, over 4 days at 4°C, and over 23 days at -20°C. The recommended expiry date was determined on the basis of time to reach 90% of the initial concentration according to the fastest observed degradation rates (i.e., lower limit of 95% confidence interval). Azacitidine degradation was very sensitive to temperature but not storage container (glass vial or polypropylene syringe). Reconstitution with cold sterile water reduced degradation. At 23°C, 15% of the initial concentration was lost after 9.6 h; at 4°C, 32% was lost after 4 days; and at -20°C, less than 5% was lost after 23 days. More than 90% of the initial azacitidine concentration will be retained, with 97.5% confidence, if, during the life of the product, storage at 23°C does not exceed 2 h, storage at 4°C does not exceed 8 h, and storage at -20°C does not exceed 4 days. These expiry dates could substantially reduce wastage and cost where the time between doses does not exceed 4 days.

Comparison of the effect among different proportion of local anesthetic spinal anesthesia in cesarean section

Objective To explore the advantages and disadvantages of different local anesthetic subarachnoid block in patients with cesarean section.Methods 120 patients to be in the spinal-epidural cesarean section down,were randomly divided into 3 groups(n =40):lighter than restructuring( Q group),so the proportion of(D),heavy weight ( Z group).Q Group:0.75 ％ bupivacaine 2ml + sterile water for injection 1ml,D group:0.75 ％ bupivacaine 2ml + CSF 1 ml,Z group:0.75％ bupivacaine 2ml + 10％ glucose,1 ml,2ml of each group were given(10mg).Characteristics in each group anesthesia,blood pressure,heart rate,complications and postoperative neurological effects were observed.Results Three groups made the same anesthesia,patients satisfaction with anesthesia had no significant difference.Z group was significantly improved compared with block group D and Q group( t =8.3,7.3,all P ＜ 0.05 ),Z group was the highest plane analgesia group than the high D and Q,Z group was significantly longer than the duration of sensory block and Q group(P ＜0.05),Z group and D duration of sensory block had no significant difference.Z group was significantly greater than the impact of the cycle Q and D groups.Anesthesia hypotension,nausea and vomiting,weight was significantly lighter than the restructuring,such as the proportion of high group.Conclusion Cesarean section in the three groups in the proportion of different local anesthetic achieved the same anesthesia,and spinal anesthesia and other medication had the proportion of liquid single,and it was relatively simple,safe and more suitable for cesarean section anesthesia. Key words: Bupivacaine ; Cesarean section ; Anesthesis, spinal ; Hypobaric ; Isobaric ; Hyperbaric

Stability and preservation of a new formulation of epoprostenol sodium for treatment of pulmonary arterial hypertension

BackgroundThe aim of this study was to evaluate the stability and microbiological properties of a formulation of epoprostenol sodium with L-arginine and sucrose excipients (epoprostenol AS).MethodsThe stability of the reconstituted solutions after storage at 5°C and 25°C, diluted solutions (3000–60,000 ng/mL) at controlled room temperature, and diluted solutions (3000–60,000 ng/mL) stored at 5°C and then at room temperature were evaluated. Solutions were prepared using sterile water for injection or sterile saline (sodium chloride 0.9%) for injection. Shelf-life was assessed by determining potency over time relative to initial potency. In this context, potency is synonymous with content. The antimicrobial activity of reconstituted (100,000 ng/mL for 0.5 mg vial, 300,000 ng/mL for 1.5 mg vial) and diluted (3000 ng/mL) epoprostenol AS was measured using an antimicrobial effectiveness test after inoculation with six species of bacteria, yeast, and mold.ResultsReconstituted epoprostenol AS was stable for up to one day’s storage at 25°C or 7 days’ storage at 5°C. Epoprostenol AS was stable for up to 72 hours when diluted, depending on temperature and concentration. The maximum shelf-life of the diluted solution if the reconstituted solution had been stored for up to one day at room temperature or up to 7 days at 5°C, was between 24 and 72 hours, depending on concentration. Following storage of diluted solutions at 5°C for up to 8 days, maximum shelf-life was between one and 2 days, depending on temperature and concentration. Potency was not dependent on diluents. Preservative testing confirmed no microbial growth for any of six organisms tested for at least 14 days at 5°C or 25°C for the reconstituted solution and for at least 16 days at 5°C followed by one day at 25°C for the diluted solutions.ConclusionEpoprostenol AS has favorable thermal stability and does not support the growth of any micro-organism tested for up to 17 days. This extended stability under ambient conditions has the potential to improve convenience further for patients.

Stability and microbiological properties of a new formulation of epoprostenol sodium when reconstituted and diluted

PurposeEpoprostenol, used for the treatment of pulmonary arterial hypertension (PAH), has a number of limitations related to its short half-life in aqueous solution. The aim of this study was to evaluate the stability and microbiological properties of a new formulation, namely epoprostenol sodium with arginine and mannitol excipients (epoprostenol AM; Veletri®; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland).MethodsStability and microbiological properties of epoprostenol AM were investigated at 5°C, 25°C, and 30°C over a range of concentrations (3000–30,000 ng/mL) when reconstituted and immediately diluted with sterile water for injection (SWI) or sterile saline (sodium chloride 0.9%) for injection (SSI). Stability (change in potency over time) for up to 72 hours at 25°C and 30°C was measured immediately following dilution and after storage at 5°C. Shelf-life was assessed by determining the maintenance of potency over time relative to initial potency. For microbiological testing, diluted samples of epoprostenol AM were inoculated with a range of bacteria, yeasts, and molds for up to 14 days at 5°C or 4 days at 25°C.ResultsEpoprostenol AM reconstituted and immediately diluted to the required concentration with SWI or SSI was stable for up to 3 days at 25°C and up to 7 days at 5°C depending on the concentration. None of the diluted epoprostenol AM solutions supported microbial growth for any of the six organisms tested for up to 14 days.ConclusionsEpoprostenol AM has improved thermal stability and does not support the growth of any microorganism tested for up to 14 days. This extended stability under ambient conditions has the potential to improve convenience for patients.

Sleep Health Problems in Adolescents

Aluminum hydroxide is the only adjuvant for use in human vaccines. The commercial alum-adjuvanted vaccines are formulated as liquid without exception. We prepared an alum-adjuvanted dry powder vaccine and demonstrated that it provided good protection for plague. The preparation strategy is simple and effective and can be carried out in a large scale. The dry powder vaccine can be quickly reconstituted using sterile water for injection. The dry powder vaccines have potential advantages over liquid vaccines, including good stability and extended shelf life.

Stability of Cefazolin Sodium in Polypropylene Syringes and Polyvinylchloride Minibags

Cefazolin is a semisynthetic penicillin derivative with a narrow spectrum of activity covering some gram-positive organisms and a few gram-negative aerobic bacteria. To determine the physical and chemical stability of cefazolin sodium reconstituted with sterile water for injection and stored in polypropylene syringes or diluted with either 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in polyvinylchloride (PVC) minibags. Reconstituted solutions of cefazolin (100 or 200 mg/mL) were packaged in polypropylene syringes. More dilute solutions (20 or 40 mg/mL) were prepared in D5W or NS and packaged in PVC minibags. For each concentration-diluent-container combination, 3 containers were designated for each day of analysis (days 7, 14, 21, and 30). Containers were stored under refrigeration (5°C) with protection from light until the designated day of analysis, at which time one 5-mL sample was collected from each the designated container. The designated containers were then stored at room temperature (21°C to 25°C) with exposure to light for an additional 72 h, and additional samples were drawn. The samples were assayed using a validated, stability-indicating high-performance liquid chromatography method. The colour and clarity of the solutions, as well as their pH, were also monitored on each sampling day. All samples remained clear for the duration of the study; they had a slight yellow colour that darkened over time, and there was an increase in pH. Solutions diluted with sterile water for injection and stored in polypropylene syringes retained at least 94.5% of the initial concentration after 30 days of refrigerated storage and at least 92.1% after an additional 72 h at room temperature with exposure to light. Samples diluted in D5W or NS and stored in PVC minibags retained at least 95.8% of the initial concentration after 30 days of refrigerated storage and at least 91.8% after an additional 72 h at room temperature with exposure to light. Cefazolin at various concentrations stored in polypropylene syringes or PVC minibags was stable for up to 30 days with storage at 5°C with protection from light, followed by an additional 72 h at 21°C to 25°C with exposure to light.

Visual compatibility of common nebulizer medications with 7% sodium chloride solution

The visual compatibility of hypertonic saline solution with various other drugs used for nebulizer therapy in cystic fibrosis (CF) was assessed. Nebulized hypertonic saline solution has proved to be an effective adjunctive therapy for management of CF-related respiratory symptoms. Admixing of hypertonic saline solution and standard medications for nebulizer delivery has been suggested as a way to reduce the time-treatment burden on patients with CF, but that practice has been discouraged due to concerns about potential incompatibilities that could lead to precipitate formation (in the nebulizer or airway) and impeded drug delivery. For the study described here, visual and turbidimetric testing was conducted to assess the compatibility of admixtures of hypertonic saline solution and 11 medications widely used in CF (acetylcysteine, albuterol, atropine, cromolyn sodium, dexamethasone, glycopyrrolate, ipratropium, metaproterenol, sodium bicarbonate, terbutaline, and tobramycin). Three samples each of admixtures of the 11 drugs and 7% sodium chloride (experimental samples) or sterile water for injection (control samples) were prepared. The testing procedure entailed four turbidimetry measurements obtained at 15-minute intervals, as well as visual checks for signs of incompatibility (e.g., haze, particle or gas formation, alteration of color); analysis of variance was used to evaluate differences in test results between the experimental and control samples. Ten of the 11 medications assessed were visually compatible with 7% sodium chloride solution, as determined by serial turbidimetric testing and visual inspection; only cromolyn sodium was found to be visually incompatible with hypertonic saline. Eleven medications used in nebulizers for the treatment of CF were visually compatible with 7% sodium chloride solution.