Stock Bottle Research Articles

Chemical Stability of Lorazepam Oral Solution Repackaged in Plastic Oral Syringes at Room and Refrigerated Temperature.

Purpose: Generic lorazepam oral solution is supplied in a 30 mL multi-dose bottle requiring protection from light and refrigeration, with a beyond use date of 90 days once the bottle is opened. The repackaging of 1 mL doses of lorazepam oral solution into oral syringes allows for facilitated dispensing, yet no available data supports repackaging and storing lorazepam oral solution in syringes. The validation and application of a stability-indicating high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for the quantification of lorazepam allowed for the determination of the stability of lorazepam oral solution when stored in oral syringes. Methods: A stability-indicating HPLC-UV method was developed for the quantification of lorazepam in oral solution. The method was validated using guidance from USP < 1225 >. For the stability investigation, 2 mg/mL lorazepam oral solution was aliquoted into clear plastic oral syringes in 1 mLmilliliter doses from 2 multi-dose stock bottles and randomly allocated for storage in room temperature or refrigerated environment. Baseline lorazepam concentrations were measured on the day the study was initiated and designated as 100% initial concentration samples. Subsequent samples were analyzed in triplicate at time points of 24, 48, and 96 hours and 7, 10, 14, 21, 30, and 60 days. Results: The calibration curves on three non-consecutive days met the linearity criteria of R 2 > 0.99. Inter- day and intra-day precision and accuracy (percent relative standard deviation and percent error) were ≤2% over three days. During the stability investigation, percent initial concentration of lorazepam from room and refrigerated syringes remained above 90% for the duration of the study. Conclusion: The stability-indicating HPLC-UV method was successfully applied to the investigation of lorazepam oral solution stability when stored in syringes at room and refrigerated temperatures. The emergent need for use of lorazepam concentrate for inpatients and the restrictions of how the medication is supplied necessitated a need for the evaluation of repackaging into unit dose syringes for immediate availability from automated dispensing cabinets. Lorazepam oral solution stored in clear plastic syringes maintained greater than 90% initial concentration at both room and refrigerated temperatures for 60 days.

Reduction of Eyedrop Volume for Topical Ophthalmic Medications with the Nanodropper Bottle Adaptor.

To determine the drop volume and total number of dispensed drops using the Nanodropper eyedrop bottle adaptor (Nanodropper, Inc.) compared to drops dispensed from stock bottles to potentially limit ocular toxicity of these eyedrops and prolong bottle use. Six topical ocular hypotensive medications (5 solutions, 1 suspension), one steroid (suspension) and two artificial tears emulsions were selected for this study. An analytical balance was used to determine the mass per 10 drops with and without the volume-reducing adaptor and repeated until the bottles were completely emptied. The density of each product was determined using the calculated density. The average drop volume and number of drops per bottle for the nine medications were compared with and without the adaptor with paired t-testing. When all medications were assessed, the drops delivered with the adaptor were 62.1% smaller than eyedrops administered from standard bottles. Compared to stock bottle eyedrops, which had a mean volume of 39.8 ± 2.1 μL, the adaptor resulted in drops with a mean volume of 15.1 ± 1.0 μL, p<0.0001. The adaptor delivered 2.6x the number of drops dispensed from a standard 2.5 mL bottle (184.1 ± 15.1 drops with adaptor and 69.8 ± 4.9 drops from stock bottle, p<0.0001). The Nanodropper eyedrop bottle adaptor can significantly reduce drop volume and increase the overall number of drops dispensed compared with stock eyedrop bottles. Further studies are needed to elucidate the clinical impact of utilizing decreased drop volume with direct comparison to current standards of care.

Design and evaluation of an application-based pharmaceutical calculations review module

Background and purposeTo describe the design of an application-based calculations review module, determine retention of skills learned in a calculations course, determine student ability to identify information necessary to solve calculations, and evaluate student perceptions. Educational activity and settingThree student cohorts completed the calculations application-based review module. All students passed a required pharmaceutical calculations course previously (17 months prior for Cohort 1 and nine months prior for Cohorts 2 and 3). The activity included seven themed stations each with three questions. Each question was categorized by calculation type. Students utilized stock bottles and patient chart information to solve problems. For select stations, necessary information was missing, and students had to request it. Each student completed an activity evaluation form. FindingsTwo hundred ninety students completed the module (90, 102, and 98 in Cohorts 1, 2, and 3, respectively). Two hundred eighty students (97%) completed the activity assessment form. The overall average score was 85.1%, which did not differ significantly among the cohorts. Cohort 1 performed significantly lower on dosage, unit conversion, ratio, and milliosmole calculations. Almost all (96.4%) students agreed the activity reinforced lecture material, and 90% agreed the activity improved their ability to perform in future pharmacy practice. Participating students scored significantly higher on a pre-graduation math skills assessment. SummarySome calculation types, such as dosage, unit conversion, ratio, and milliosmoles may warrant more closely spaced reinforcement activities in the curriculum. Inclusion of the review module was associated with increased knowledge retention.

Stability Determination of an Extemporaneously Compounded Ambrisentan Suspension by High Performance Liquid Chromatography Analysis

Ambrisentan, an endothelin receptor antagonist FDA-approved for the treatment of pulmonary arterial hypertension in adult patients, lacks an acceptable pediatric dosage form. The objective of this investigation was to determine the stability of an extemporaneously compounded ambrisentan suspension. Ambrisentan suspension was compounded to a concentration of 1 mg/mL using commercially available suspending agents. The suspension was then evenly split into 2 plastic amber prescription bottles. One bottle was stored at room temperature and under continuous fluorescent light while the other bottle was stored under refrigeration and protection from light. A fast and selective reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ambrisentan. HPLC analysis was performed on samples withdrawn from the stock bottles at predetermined time intervals, up to 90 days. The developed HPLC method enabled the elution and detection of ambrisentan peak at 4.4 minutes. HPLC analysis revealed that all samples from both storage conditions retained >90% potency throughout the study timeframe. There were no signs of any ambrisentan breakdown products on HPLC analysis. Color and odor of the final product was also consistent throughout the 90-day storage period. Ambrisentan suspension, compounded to 1 mg/mL, is stable at room temperature or under refrigeration for up to 90 days.

Strength and Sterility of Stock and Diluted Carprofen Over Time.

Carprofen, a nonsteroidal antiinflammatory drug, is a commonly used analgesic for laboratory animals. The manufacturer labeling indicates the stock bottle may be stored and used for up to 28 d under refrigeration. However, institutional guidelines may vary in how long diluted carprofen solutions can be stored before they must be discarded. When administered to laboratory rodents, small volumes of the stock solution are diluted to provide accurate dosing and ease of administration. Because carprofen is formulated for use in companion animals (for example, dogs) and comes in larger volume multidose vials, the majority of carprofen at our institution is discarded before it can be used. In this study, we evaluated the amount of target ingredient present (strength), sterility, and endotoxin levels of both stock and diluted carprofen when stored in a variety of containers and at multiple temperature settings for up to 180 d, mimicking facets of typical use in laboratory animal research and medicine. We demonstrated that when refrigerated and stored in sterile vials, stock and diluted carprofen can be kept and used for up to 180 d while retaining strength and sterility. For short-term use, diluted carprofen can also be stored for up to 60 d at room temperature in conical tubes. These results will help establish scientifically justified storage conditions for carprofen to ensure that these agents remain appropriately potent and sterile for therapeutic use in laboratory animals.

A new record of genus Zercon (Acari, Zerconidae) for Turkish Fauna: Zercon saphenus Błaszak, 1979

The zerconid mites collected from Kovada Lake National Park (Isparta province) in 20 March 2018 were evaluated. Collected samples were placed into plastic bags, labelled and transferred to the laboratory. Samples were placed into combined Berlese funnels and mites were extracted for 5–7 days according to their humidity. Mites were separated under a stereo-microscope. They were placed in 60% lactic acid for clearing and mounted onto permanent microscope slides using a glycerin medium. Then, the samples were put in stock bottles containing 70 % alcohol and 1- 3 drops glycine and labelled. Zercon saphenus was recorded as new for the Turkish mite fauna. Also, deutonymph and protonymph specimens of Z. saphenus were described for the first time from Turkey. Keywords : Acari, Zerconidae, Zercon saphenus, Systematic, Turkey. DOI : 10.7176/JSTR/5-3-03

1253. Healthcare-Associated Transmission of Burkholderia cepacia Complex Associated With Extrinsically Contaminated Nasal Spray

Background Burkholderia cepacia complex (Bcc) species can contaminate medical devices and water-based products, resulting in outbreaks of healthcare-associated infections. In March 2018, we investigated a cluster of 20 patients with a sinus culture positive for Bcc seen at two affiliated ENT clinics in Oregon over a 2-month period, based on reporting by a laboratorian in a central laboratory external to the clinics.MethodsWe conducted an epidemiologic investigation to identify potential causes for an apparent outbreak of Bcc, including review of health records and microbiologic reports, site visits, staff interviews, and cultures of common equipment and products.Results20 patients (9 were female; age range 10 to 72 years, median age 54.5 years) had new positive Bcc cultures from the sinus. The absence of cystic fibrosis, immunosuppression or sinonasal polyposis in all patients, scant growth of Bcc in most cases with isolation of another organism in some, and the use of Bcc-directed antibiotics in a minority of patients suggested the presence of a contamination source. All patients had received lidocaine/phenylephrine (L/P) via multidose nasal spray atomizers prior to endoscopically-directed sinus cultures. Site visits revealed improper medication dispensing and storage practices (e.g., no expiration date for L/P stock, storage of L/P-containing atomizers at room temperature), and inadequate instrument reprocessing and environmental cleaning. Cultures of L/P in 2/2 in-use atomizers and 1/1 opened stock bottle, as well as swabs of 3/3 spray mechanisms, grew Bcc. Cultures of L/P from the unopened, refrigerated stock bottle, a flexible endoscope and a rigid endoscope did not yield Bcc. No negative clinical sequelae in these patients were reported.ConclusionContaminated multidose L/P nasal spray with Bcc resulted in nosocomial transmission at these clinics. This investigation highlights the important role of laboratorians in detecting Bcc contamination events that lead to colonization, and suboptimal reporting by clinicians in the outpatient setting. It also raises the question of how often such contamination events go undetected. Injection safety training needs to be broadened to “medication administration safety” training as one and only principles could have prevented this incident.Disclosures All authors: No reported disclosures.

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering.

The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

Microbiological evaluation of open and sealed tattoo inks

Background. Introduction of tattoo inks in the skin has been associated with a potential entry of a great number of microorganisms including bacteria, virus and fungi. Contaminated pigments, diluents and instruments represent primary infection risk factors as well as inadequacy of hygienic measures during this practice. However, the evaluation of the infectious risk for public health due to tattoo ink use is actually not feasible cause of the low efficiency of health surveillance and the lack of specific regulation in this area.Materials and Methods. A survey was carried out to test the microbial product safety of some tattoo inks available in Italian tattoo parlours. Physical packaging and labelling of the collected inks were also examined. Newly acquired sealed stock bottles, open ink bottles and tattoo-correlated instruments (needles, spikes and grips) were collected and tested for different microbiological parameters. Results. Both from opened and sealed inks a variety of potentially pathogenic organisms were isolated and identified including Gram positive rods and cocci, Gram negative bacteria and fungi. Different species of Bacillus and Staphylococcus genera were identified, among which S. haemolyticus; Cronobacter sakazaki, Enterobacter intermedius and Sphingomonas paucimobilis were also identified while no atypical mycobacteria were isolated. Needles, spikes and grips tested for sterility were aseptic.Conclusions. Microbial contamination of opened samples suggest inefficacy of preservatives and additives in maintaining inks hygienic quality, and inadequacy of hygienic procedures during the tattooing operations, while the occurrence of microorganisms in unopened samples put in doubt the effectiveness of the sterilization technology applied to this type of product.

Microbial status and product labelling of 58 original tattoo inks

European Council resolutions on tattoo ink introduce sterility and preservation of inks to protect customers. Inks used in Denmark are typically purchased over the internet from international suppliers and manufacturers from the US and the UK. In Denmark tattoo inks are regulated and labelled according to REACH as if they were plain chemicals. The objective of this study was to check the microbial product safety of unopened and opened tattoo ink stock bottles. Packaging, labelling, preservation, sterility and contamination with micro-organisms were studied. Physical inspection and culture of bacteria and fungi. Six of 58 unopened stock bottles (10%) were contaminated with bacteria and one of six samples (17%) of previously used stock bottles was contaminated. The bacterial species represented bacteria considered pathogenic in humans as well as non-pathogenic environmental bacteria. Yeast or moulds were detected in none of the samples. A total of 31% of the manufacturers informed only about the brand name. No information about content, sterility, risks or expiry date was indicated on the label. A total of 42% claimed sterility of their inks. A total of 54% labelled a maximum period of durability of typically 2-3 years. The physical sealing was leaking in 28% of the products. The European Council resolutions regarding safety of tattoo inks are not effective. Stock bottles of tattoo ink may contain bacteria pathogenic to humans and environmental bacteria, and packaging, labelling and preservation of inks are of inadequate quality. Claim of sterility can be erroneous.

A Chryseobacterium meningosepticum outbreak in a neonatal ward.

To report epidemiologic, bacteriologic, and clinical features of a Chryseobacterium meningosepticum outbreak. Outbreak investigation. A neonatal intensive care unit (NICU) of a referral teaching hospital. During 2 weeks in September 2001, four neonates in the NICU developed sepsis and underwent laboratory investigation. Multiple samples were obtained for cultures from endotracheal tubes, mechanical ventilators and humidifier boxes, infant incubators, parenteral and antiseptic solutions, feeding bottles, sinks, faucets, doors, and healthcare workers. C. meningosepticum was isolated from the blood cultures of four patients. The first isolate was identified 5 days after the death of the index case. Although all isolates were ciprofloxacin susceptible in vitro, the remaining three patients did not respond to ciprofloxacin therapy given for 6 or 7 days. Therapy was switched to vancomycin and rifainpin and all three patients survived, with one having a complication (hydrocephalus). Environmental surveillance revealed C. meningosepticum in the stock lipid solution as the source of the epidemic. The outbreak was controlled after discontinuation of intravenous lipid solution, restriction of further neonatal admissions, and thorough disinfection of the unit and its equipment. Early identification of an epidemic and its source is important in avoiding morbidity and mortality. A contaminated lipid stock bottle was the source of this outbreak associated with multiple cases and one death.

IMPROVING ACCURACY IN SIMULATED PHARMACY ASSEMBLY TASKS USING WORKSPACE INTERVENTIONS TO ENHANCE THE COGNITIVE ENVIRONMENT

In this study, the error-reducing effectiveness of two work-environment interventions was examined in a simulated pharmacy task. 110 participants worked for 3 to 4 hours filling approximately 110 orders for simulated drugs in a laboratory-based, controlled environment. One group of participants used a monitor-mounted copy strip to enhance data entry, and another group used the copy strips as well as labeled product sleeves on stock bottles to enhance product selection. Results indicated that participants who worked using copy strips as well as participants who worked using both copy strips and product sleeves were more accurate in their order-filling performance than participants in the control condition. However, participants in the copy strip and the copy strip/sleeve conditions did not differ from one another in accuracy. Further research ideas and potential explanations of these data are discussed.

Neurologic complications including paralysis after a medication error involving implanted intrathecal catheters

PurposeLong-term continuous intrathecal infusion of medications for chronic medical problems is common. We investigated the cause of a cluster of severe neurologic complications in patients with intrathecal catheters. MethodsWe performed an epidemiologic cohort study of patients who had intrathecal catheters in place in one neurosurgical practice, to assess the presence of new neurologic complications and associated risk factors. ResultsThe practice included 61 patients who received pain medication through implanted intrathecal catheter pumps, 19 of whom were treated with morphine, either alone or in combination with other medications. None of the 42 patients whose drug regimen did not include morphine developed a complication, whereas 8 of 13 patients who received morphine in refills of their pumps during one 4-week period experienced neurologic complications. Three persons underwent laminectomy for sterile abscesses and were left with new paralysis or leg weakness. Testing of two stock bottles from the involved pharmacy, both labeled as containing pure morphine, revealed the presence of methadone in addition to morphine. One of these bottles also contained trace ethanol. A sample of medication aspirated from the pump of a patient prescribed morphine from the same pharmacy was also found to have contained methadone and methanol. ConclusionsA variety of severe neurologic complications was associated with inadvertent administration of methadone, and perhaps other unintended substances, by means of implanted intrathecal catheters to a group of patients. Medical errors in an outpatient pharmacy led to this outbreak.

処方オーダリングデータを利用した散剤調製監査システムの構築

A computerized support system for dispensing powder drugs was developed in connection with the prescription order entry system already in operation. This system incorporates three functions: verification of dispensing of powders, checking of refilling of powders into their stock bottles, and controlling powder dividing. During powder dispensing, the system is capable of collating the stock bottle powders with the prescribed powders, and of collating the amount of powders weighted by the pharmacist with that prescribed by the physician. When the name and amount of powders dispensed match those of the powders prescribed, the pharmacist can then dispense the next prescription. At refilling of powders into their respective stock bottles, the system which then permits the pharmacist to refill the stock bottle powders ensures the matching of the stock bottle with the original powder container. On dividing and packaging of powders using the powder divider, the system sets the diving number to powder divider, and the patient's name, prescription number and drug envelope number are printed on each unit-dose package. Checking this printed information enables the pharmacist to enclose correctly the unit-dose packages in their proper drug envelope. Since this on-line system facilitates all aspects of the powder dispensing process, we believe that it is particularly useful in preventing dispensing errors.

Prescribing by numbers

When I first went into practice 70% of all our prescriptions came out of 12 numbered stock bottles in the dispensary. Each bottle was a different colour but they all had a fascinating clarity so that the sunlight coming in through the window and shining through the bottles made brilliant patches of light on the ceiling and walls as our dispenser went about her work. Shortly after joining the practice I dared to ask her what the bottles contained. I did not know at that stage that she was the most formidable of all the members of the practice, a doctor's daughter with a degree. She told me that it was my duty to decide which bottle to prescribe for each patient and hers to decide what to put into the bottle. By long tradition each bottle was used for a certain system, or …

オンライン散剤調剤鑑査システムとその評価

A few computer systems which monitor and record processes of powder drug dispensing are now commercially available. They have now come into wide use for reconfirming dispensed drugs by monitoring the records which were input into the system by making the barcode reader read the barcode on the bottom of a picked-up stock bottle and by making the electric balance read doses weighed when the pharmacist fills the prescription. The commercial monitoring system for dispensing is usually used stand-alone, but we connected this system to the prescription order system for inpatients in the total computerized hospital information system. With this system, the prescription data ordered by physicians are printed out in the pharmacy, and at the same time, sent directly to the monitoring system device prior to dispensing. In this device this prescription information contributes to dispensing by participating as indexes for filling the proper drugs. When a dispenser picks up a different stock bottle or weighs a dose different from a prescription information, a warning message is sent to the dispenser as an alarm appers on the display, with the next dispensing step not allowed to proceed until the right drug or right dose is determined.As the result of the practical use of this on-line system, the occurrences of serious dispensing errors such as the wrong drug or dosage of prescriptions could effectively be controlled.

バーコード（医薬品元箱ＪＡＮコードと装置瓶ＮＷ７コード）を利用した散剤充填チェックシステム

バーコード（医薬品元箱ＪＡＮコードと装置瓶ＮＷ７コード）を利用した散剤充填チェックシステム

An alternative procedure for handling borane solutions

A way of handling borane solutions that does not require the use of a syringe and minimal contact with stock bottle.

A Quick and Easy Simulation of Disease Transmission

Disease transmission is always a timely topic, whether it's winter cold season, or there is an outbreak of measles, or AIDS is in the news. This demonstration involves the class in a simulation of disease transmission. Results are unambiguous and swiftly obtained, and the transmission route can be traced. Each student is given a stock bottle of solution, a clean test tube and a pasteur (disposable) pipet. All bottles contain dilute (0.001 N) HCI except one, which contains 0.1 N NaOH. This difference, of course, is not visible to the students; the affected individual has no symptoms. You could think of this solution as aerosol droplets from a sneeze, or the notorious bodily fluids whose exchange is necessary for AIDS transmission. Before beginning the procedure, remind students of standard laboratory safety practices: do not allow the solutions to come into contact with your skin or clothing; notify the instructor immediatly if a spill occurs. If a student splashes a solution on himself, flood the affected area with water. Have your acid and base spill cleanup kits on hand in case of a spilled or broken bottle.

High-efficiency dilution method of sulfuric acid prepared directly in stock bottle with cooler and stirrer

High-efficiency dilution method of sulfuric acid prepared directly in stock bottle with cooler and stirrer