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Objective: The aim of the study was to investigate the physicochemical stability of mitomycin-containing medicinal products for bladder instillation, formulated with urea as excipient (mito-medac®, Mitomycin medac). For comparison, the stability of reconstituted Urocin® and Mitem® bladder instillation was studied., Methods: Mitomycin-containing medicinal products were either reconstituted with the prepackaged 0.9% NaCl solution, nominal volume 20 mL (mito-medac®, Mitem®, Urocin®) or with 20 mL water for injection (Mitomycin medac, Mitem®, Urocin®) to a nominal concentration of 1 mg/mL and stored at room temperature (20-25°C). Samples were taken immediately after reconstitution and after 24 hours. Physicochemical stability was determined by reverse-phase high performance liquid chromatography with photodiode array detection, measurement of pH and osmolarity, and inspection for visible particles or colour changes., Results: The initial pH values of the test solutions reconstituted with prepackaged 0.9% NaCl (5.2-5.6) were significantly lower than those reconstituted with water for injection (6.6-7.4). Solutions reconstituted with 0.9% NaCl solutions rapidly degraded and concentrations fell below the 90% limit after 24 hours of storage. When reconstituted with water for injection, degradation was less rapid. Concentrations of Mitomycin medac and Urocin remained above the 90% limit after 24 hours., Conclusions: The physicochemical stability of mitomycin 1 mg/mL bladder instillation prepared with prepackaged 0.9% NaCl in prefilled PVC bags is less than 24 hours at room temperature. Unfavourable pH values of the solvents cause rapid degradation of mitomycin. Mitomycin solutions reconstituted at the point of care should be administered immediately to avoid degradation and loss of efficacy. Urea added as excipient did not accelerate degradation., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Oxytocin is the principal drug and the primary choice for labor induction and postpartum hemorrhage prevention and treatment. The problems associated with oxytocin are not usually from its effectiveness, but they are from its compromised quality which may occur at the point of manufacturing, transportation, and storage. The main objective of this study was to assess the status of oxytocin injection quality and associated factors in the health facilities located in Addis Ababa city, Ethiopia. A laboratory based instrumental quality testing alongside a cross sectional study design was used to evaluate oxytocin injection quality in Addis Ababa city administration from January to June, 2022 according to United States Pharmacopeia (USP 20), and the World Health Organization guideline of post-market medicine quality assessment. Binary logistic regression and cross tabulation analysis were conducted using SPSS 26. Significance was considered at p ≤ 0.05. Out of 107 tested oxytocin injection samples, 92.5% met the limit for oxytocin content, 81.3% for sterility test, and 91.6% for pH value. Overall, quality failure rate was 23.4%, while sterility test failure rate was 18.7%. Lack of reliable refrigerated storage condition [(AOR = 5.62, 95% CI: (1.87, 16.88)], lack of effective cold chain system during distribution [(AOR = 5.5, 95% CI: (1.53, 19.74)], and weak national medicine regulatory system [(AOR = 3.23, 95% CI: (1.13, 9.23)] were among the significantly associated factors for the failure of some of the brands. The study demonstrated that oxytocin injection quality failure rate, failing to meet at least one quality test requirement, is demonstrated in the health facilities of Addis Ababa. The determinant factors for the reported failures are related to storage, distribution, and regulatory system. Hence, these should be addressed by strictly adhering in to the national regulation and providing a comprehensive health promotion on rational use of oxytocin injection should be implemented to assure its quality and safety., (© 2024. The Author(s).)

Objective: To assess the implementation of the bedside medication preparation process in an Intensive Care Unit, following a quality improvement cycle., Method: A quasi-experimental study with non-paired samples, pre- and post-implementation, conducted in an Intensive Care Unit of a public hospital in southern Brazil, from September 2022 to April 2023, following the guidelines of the Standards for Quality Improvement Reporting Excellence 2.0. Adherence to bedside medication preparation, interruptions during preparation, adequate storage, identification and validity of multidose medications, and recording of storage refrigerator temperature were evaluated. Shapiro-Wilk and Mann-Whitney U tests were used for data analysis, and Carter's Positivity Index was used to determine compliance with observed practices., Results: Forty-five audits were conducted pre-intervention and 122 audits three months after the implementation of the improvement cycle. All variables showed significant improvements. Overall compliance increased from 46% to 80% in the pre- and post-implementation periods, respectively, indicating a transition from "undesirable" to "safe" care stratum., Conclusion: The study revealed a positive relationship between the implementation of a quality improvement cycle focused on medication preparation and improvements in patient safety.

The correct storage of vaccines is vital to ensuring that they work effectively and keep patients safe. In this article the author explains how to ensure compliance with regulations without placing an undue burden on community nursing staff.

Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single-dose biological products after first puncture and potential accidental contamination during dose preparation (e.g., reconstitution or dilution) and storage. These studies, in addition to physicochemical in-use stability assessments, are used as part of product registration to define in-use hold times in Prescribing Information and in the pharmacy manual in the case of clinical products. There are no formal guidance documents describing regulator expectations on how to conduct microbial challenge in-use studies and interpret microbial data to assign in-use storage hold times. In lieu of guidance, US Food and Drug Administration (FDA) regulators have authored publications and presentations describing regulator expectations. Insufficient or unavailable microbial challenge data can result in shortened in-use hold times, thus microbial challenge data enables flexibility for health care providers (HCPs) and patients while ensuring patient safety. A cross-industry/FDA in-use microbial working group was formed through the Innovation & Quality (IQ) Consortium to gain alignment among industry practice and regulator expectations. The working group assessed regulatory guidance, current industry practice via a blinded survey of IQ Consortium member companies, and scientific rationale to align on recommendations for experimental design, execution of microbial challenge in-use studies, and a decision tree for microbial data interpretation to assign in-use hold times. Besides the study execution and data interpretation, additional considerations are discussed including the use of platform data for clinical stage products, closed system transfer devices (CSTDs), transport of dose solutions, long infusion times, and the use of USP <797> by HCPs for preparing sterile drugs for administration. The recommendations provided in this article will help streamline biological product development, ensure consistency on assignment of in-use hold times in biological product labels across industry, and provide maximum allowable flexibility to HCPs and patients while ensuring patient safety., (© PDA, Inc. 2024.)

Objective: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear., Methods: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids., Results: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely., Conclusion: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices., (© The Author(s) 2024. Published by Oxford University Press.)

The current COVID-19 pandemic has affected the ability of health systems to provide essential services globally. The Darfur region, located in the western part of Sudan, has been largely devastated by the war that began in 2003 and has been drawing considerable attention from the international community. The war, which erupted as a result of environmental, political, and economic factors, has led to tragic outcomes. Collapsing health-care infrastructures, health workforce shortages, lack of storage facilities for medicines and medical products, and inadequate access to health services are some of the effects of the war. After Sudan received the AstraZeneca COVID-19 vaccine through the COVID-19 Vaccines Global Access facility, significant challenges have been implicated in the delivery, storage, and use of the vaccine in the Darfur region. Lack of vaccine storage and transportation facilities, vaccination hesitancy, inequity in the distribution to health facilities, and shortage of health-care professionals resulting from insecurity and instability have added an extra layer of burden on local authorities and their ability to manage COVID-19 vaccinations in the region adequately. Addressing the impact of COVID-19 requires an effectively managed vaccination program. In the face of current challenges in Darfur, ensuring a fully vaccinated population might remain far-fetched and improbable if meaningful efforts are not put in place by all stakeholders and actors to address some of the challenges identified.

Objectives: To evaluate caregivers' practice of prescription medication storage, particularly of opioid medications, as well as to provide educational materials to families about the opioid crisis., Methods: Caregivers of patients in a pediatric emergency department were asked to participate in a survey about medication storage practices and beliefs, focusing on opioid medications. Data were collected through a survey documenting demographic data along with knowledge and behaviors of medication storage. Brief education about the US opioid crisis and safe storage was provided., Results: In total, 233 families participated; 3 families declined; 11.5% of caregivers reported storing prescribed medications in a locked or latched place, although most store them "out of reach." Most believed their child or children's friends could not easily access their medications (81.8%). Families who did not keep their medications in locked or latched places had never thought about it (39.7%). In total, 33% of respondents were unaware of the opioid crisis; 87.4% of caregivers said they would use a medication lock box if given one., Conclusions: Many caregivers are not aware of the opioid crisis and do not keep opioid medications locked up. Half of the caregivers surveyed stated they "never thought about" locking up medications. Most parents would use a lock box if given to them. This opens the door to further study, education, and interventions.

Introduction: Antibiotics are commonly used for the treatment and prevention of bacterial infections. The potency of antibiotics can be affected by factors such as temperature, light, moisture, and storage conditions. Inappropriate storage and transportation of antibiotics may lead to loss of potency earlier than the expiry date. The aim of this study was to determine the potency and associated factors of commonly retailed antibiotics., Method: Institution-based cross-sectional study was conducted on commonly retailed antibiotics in pharmacies that are available in Adama, Ethiopia from March 2018 to June 2018. This study focused on commonly ordered antibiotics such as amoxicillin, azithromycin, ciprofloxacin, and ceftriaxone. Antibiotics to be tested were selected by using a simple random sampling technique. Socio-demographic and related data were collected using a semi-structured questionnaire. Antibiotic susceptibility testing was performed using the disc diffusion method as described in the Clinical Laboratory Standard Institute guideline., Results: Mean inhibition zones of amoxicillin, ciprofloxacin, azithromycin, and ceftriaxone were 14.2 ± 4 mm, 30.9 ± 4.2 mm, 17.47 ± 3.83 mm, and 32.7±1.8 respectively. Out of 164 antibiotics tested, 61% passed the potency test. The potency of antibiotics varies across different countries in which 53.7% and 54.6 of antibiotics from India and Ethiopia passed the potency test. All ceftriaxone tested in this study passed the potency test. Factors such as air condition of pharmacy (X2 = 4.27; p = 0.039), source of all antibiotics (X2 = 5.41; p = 0.02), and source of amoxicillin (X2 = 4.73; p = 0.03) were significantly associated with potency of antibiotics., Conclusions: About 40% of antibiotics tested in the current study did not pass the potency test; this warrants further investigation to identify the magnitude of the problem and its causes at a large scale., Competing Interests: No authors have competing interests.

Objectives: This study aims to determine the effect of opioid-specific counseling on postdischarge opioid consumption and opioid storage/disposal patterns after reconstructive pelvic surgery., Methods: In this multicenter randomized-controlled trial, participants were randomized to standard generalized counseling or opioid-specific perioperative counseling. Opioid-specific counseling was provided at the preoperative and 2-week postoperative visits with educational handouts about the risks of opioids and U.S. Food and Drug Administration recommendations for appropriate opioid storage and disposal. The primary outcome was morphine milligram equivalent (MME) consumption between hospital discharge and 2 weeks postoperatively. Secondary outcomes included opioid storage 2 weeks postoperatively, opioid disposal 6 weeks postoperatively, and rate of opioid refills., Results: Among 70 opioid-specific and 65 standard counseling participants, there were no significant differences in demographic characteristics, type of surgery, concomitant hysterectomy, or perioperative complications. For the primary outcome, there was no significant difference in median opioid consumption between the 2 arms. Median (interquartile range) postdischarge MME consumption for all participants was 15 mg (0-75). Forty percent of participants denied postdischarge MME consumption. For secondary outcomes, there were no significant differences in appropriate opioid storage between groups. The appropriate disposal rate of unused opioid tablets 6 weeks after surgery was higher among participants who received opioid-specific counseling. The rate of opioid refill was 7.4%., Conclusions: Opioid-specific counseling did not affect postdischarge consumption but increased the disposal rate of unused opioid tablets 6 weeks postoperatively. Opioid-specific counseling could minimize the potential for opioid misuse by reducing the number of unused opioid tablets in patients' possession after surgery., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Purpose: Diazepam is utilized as a convulsion antidote following nerve gas attacks. As an emergency medicine, it requires storage at ambient temperatures which often doesn't meet manufacturers' requirements, leading to an early invalidation of the product. Current work investigated this issue., Methods: Long-term stability of diazepam ampoules for injection stored in an ambient temperature of the Mediterranean climate for ~10 years vs storage at room temperature was studied., Results: Diazepam assay and pH remained within pharmacopeial specifications irrespective of storage conditions. A major degradation product 2-methylamino-5-chlorobenzophenone (MACB) showed a clear trend of accumulation as a function of storage time, exceeding the permitted limit at ~2 years, irrespective of storage conditions. A strong correlation between the discoloration of the solutions and the concentration of MACB was obtained. Intravenous administration of MACB to rats at doses ~2200-fold higher than permissible specification levels caused neither mortality nor any toxicological nor post-mortem findings., Conclusions: Regarding the parameters tested: diazepam assay, MACB assay, and pH, storing ampoules of diazepam solution for injection in field conditions of high temperatures of the Mediterranean climate did not cause accelerated degradation as compared to room temperature. These findings open an option for the usage of expired ampoules in special scenarios.

Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2-8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2-121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5-48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Results of a study to quantify rates of identification of expired medications in automated dispensing cabinets (ADCs) are reported., Methods: A pre-post analysis was conducted to determine the effect of various types of ADC audits on rates of finding expired medications in ADCs. For the experimental phase of the study, 4 ADCs at the main campus of an academic medical center were randomly assigned to receive one of 4 interventions: (1) monthly audits of all ADC pockets, (2) monthly audits of matrix (open pocket) drawers only, (3) monthly audits of unassigned pockets only, and (4) no additional intervention., Results: At baseline, rates of finding expired medication doses in the 4 ADCs ranged from 0.4% to 0.7%. During the 3-month experimental period, rates of finding expired medication doses ranged from 0.1% to 0.3%. During a final audit 1 month later, the ADC targeted for monthly audits of all pockets was found to contain no expired doses, with an overall improvement in expired-dose rates for all audited ADCs observed over the course of the 4-month study. The average time to perform a full audit for an ADC with about 340 pockets was 1 hour, or 15 seconds per pocket. The average time to perform matrix drawer-only audits averaged around 45 minutes, or 11 seconds per pocket. The average time to perform audits of unassigned matrix drawers averaged 30 minutes, or 10 seconds per pocket., Conclusion: Auditing of all ADC pockets on a monthly basis appears to be an effective method of reducing the rate of identification of expired medications in ADC pockets., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: inspite of the demonstrable evidence of the preventive and protective ability of vaccines to reduce the outbreak of vaccine-preventable diseases, there are still some significant disease outbreaks recorded in our communities. In some settings, these outbreaks have been linked with poor vaccine management. Therefore, this study was conducted to compare the cold chain practices in Oyo State, Nigeria., Methods: we conducted a cross-sectional survey among health workers in the local government areas of Oyo State between October and November 2019. Using purposive sampling, we recruited all the 84 routine immunization focal persons for the study. A self-administered questionnaire was used to collect data on cold chain management. Data were analyzed using SPSS version 24 and bivariate analysis was done using Chi-square. Statistical significance was set at p < 0.05., Results: the mean age of the respondents was 46.4 ± 6.7 years. Most prevalent cadre in the rural facilities was health assistants (87.5%) while Community Extension Health Workers (54.8%) were prevalent in the urban (p = 0.002). The proportion of respondents with adequate cold chain equipment was significantly higher in the urban compared with the rural area. The cold boxes were the only adequate cold chain equipment found in the rural health facilities compared with the urban (p = 0.036)., Conclusion: there was a low proportion of qualified health workers and inadequate cold chain equipment in the rural area compared with the urban facilities. Engagement of skilled health workers and supply of the cold chain equipment are recommended., Competing Interests: The authors declare no competing interests., (Copyright: Olaniyan Akintunde Babatunde et al.)

Spoiled perishable products, such as food and drugs exposed to inappropriate temperature, cause million illnesses every year. Risks range from intoxication due to pathogen-contaminated edibles, to suboptimal potency of temperature-sensitive vaccines. High-performance and low-cost indicators are needed, based on conformable materials whose properties change continuously and irreversibly depending on the experienced time-temperature profile. However, these systems can be limited by unclear reading, especially for colour-blind people, and are often difficult to be encoded with a tailored response to detect excess temperature over varying temporal profiles. Here we report on optically-programmed, non-colorimetric indicators based on nano-textured non-wovens encoded by their cross-linking degree. This combination allows a desired time-temperature response to be achieved, to address different perishable products. The devices operate by visual contrast with ambient light, which is explained by backscattering calculations for the complex fibrous material. Optical nanomaterials with photo-encoded thermal properties might establish new design rules for intelligent labels.

Providing vaccines places a significant logistical and financial burden on an office but is important in providing care to patients. Start the process by finding a vaccine champion, choosing a primary and backup vaccine coordinator, and creating a team in the office to promote and administer vaccines. Follow best practices when storing and monitoring vaccines. Create office policies for ordering vaccines in a fiscally sound manner, accepting deliveries, and managing inventory. Have backup processes in place to avoid preventable errors when administering vaccines. In addition, bill vaccine administration codes appropriately to collect the full reimbursement that is due., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, sodium edetate, sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.

Background: . Intravitreal administration of topotecan shows activity against tumor vitreous seeding in the conservative treatment of retinoblastoma, a malignant tumor originated in the retina of small children. Adequate storage of the intravitreal topotecan solution would allow immediate availability for patients at health care institutions. The goal of the work was to address the stability of the intravitreal topotecan formulation upon reconstitution., Materials and Methods: . Intravitreal topotecan solutions were reconstituted (at a concentration of 0.2 mg topotecan in 1 mL saline solution vehicle, aliquoted in 1 mL plastic syringes) and stored either frozen or at room temperature for different times. Topotecan content was analyzed at time zero and at different conditions using a high performance liquid chromatography method to quantify topotecan lactone (active) and to detect its pH-dependent hydrolysis product, the open carboxylate., Results: . We found that intravitreal topotecan syringes remained stable at room temperature at least for 24 h, at least for 167 days upon stored frozen at -20°C, and up to 8 h after thawing at day 6. The degradation carboxylate product did not appear in the analyzed thawed samples during the whole study., Conclusions: . This study confirms the stability of frozen intravitreal topotecan syringes and will help optimize the use of this chemotherapy modality at institutions with low resources. Storage of aliquots will also help reduce personnel exposure to chemotherapy at hospital pharmacies.

Lipid-shelled microbubbles have received extensive interest to enhance ultrasound-responsive drug delivery outcomes due to their high biocompatibility. While therapeutic effectiveness of microbubbles is well established, there remain limitations in sample homogeneity, stability profile and drug loading properties which restrict these formulations from seeing widespread use in the clinical setting. In this review, we evaluate and discuss the most encouraging leads in lipid microbubble design and optimisation. We examine current applications in drug delivery for the systems and subsequently detail shell compositions and preparation strategies that improve monodispersity while retaining ultrasound responsiveness. We review how excipients and storage techniques help maximise stability and introduce different characterisation and drug loading techniques and evaluate their impact on formulation performance. The review concludes with current quality control measures in place to ensure lipid microbubbles can be reproducibly used in drug delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hydrastis canadensis, commonly known as goldenseal, is a botanical native to the southeastern United States that has been used for the treatment of infection. The activity of goldenseal is often attributed to the presence of alkaloids (cyclic, nitrogen-containing compounds) present within its roots. Chemical components of botanical supplements like goldenseal may face degradation if not stored properly. The purpose of the research was to analyze the stability of known and unknown metabolites of H. canadensis during exposure to different storage conditions using mass spectrometry. Three abundant metabolites of H. canadensis , berberine, canadine, and hydrastine, were chosen for targeted analysis, and the stability of unknown metabolites was evaluated using untargeted metabolomics. The analysis and evaluation of H. canadensis samples were performed utilizing LC-MS and Principal Component Analysis (PCA). The research project focused on identifying the chemical changes in the metabolite content of H. canadensis under different temperature conditions (40°C ± 5°C, 20°C ± 5°C , and 4°C ± 5°C), different light:dark (hr:hr) cycles (16:8, 12:12, and 0:24), and different sample conditions (powdered roots versus whole roots) over a six month period. The results of this 6-month study revealed that the storage conditions evaluated had no significant effects on the chemical composition of H. canadensis roots. Hence, as long as H. canadensis roots are stored within the storage conditions tested in the study, no significant changes in chemical compositions of metabolites are expected., (Copyright ©2020, Yale Journal of Biology and Medicine.)

Background: The inadequate storage of biopharmaceuticals may result in an ineffective therapeutic response since poor conservation can lead to the emergence of protein aggregates and cause immunogenicity in patients, which can increase the risk of adverse events by inducing the production of anti-drug antibodies. This can also lead to significant economic losses for public health, given the high cost of these medicines. The aim of this study was to verify whether the home storage of biopharmaceuticals dispensed by the Unified Public System was in accordance with the manufacturers' specified standards and whether external variables interfered with the correct home storage., Methods: This was a prospective observational study. Patients with a confirmed diagnosis of rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis who were using a biologic exclusively dispensed by Unified Public System were included. Storage temperature was measured by digital thermometer inserted into the refrigerator of the participant's home. Fisher's exact test was performed to cross-reference the temperature data and the qualitative variables obtained using an epidemiologic questionnaire. Mean, minimum, maximum values and standard deviation were described in the quantitative data. Mann-Whitney non-parametric test was performed to the association between temperature excursion and the number of people in the house., Results: A total of 81 participants were included and 67 (82.71%) did not maintain home storage correctly. The maximum temperature observed among all patients was 15.5 °C, the minimum was - 4.4 °C and the average was 5.6 °C (standard deviation 2.8); 10 (12.3%) had at least one negative temperature measured. The average time for participants who had an inadequate temperature record was 8 h and 31 min. Nine participants (90%) who stored the medication into the shelf/drawer below the freezer had a temperature excursion (p = 0.011). Most of the participants (88.5%) who stored their biopharmaceutical near the back side, close to the wall of the refrigerator had a negative temperature record (p < 0.001)., Conclusion: Most of the study participants (82.71%) did not maintain adequate home storage conditions for their biopharmaceutical. Intrinsic factors of household refrigerators may be involved in temperature deviations.

Epinephrine autoinjectors (EAIs) are important first aid medications for treating anaphylaxis. A 10-fold price increase over the past 12 years and evidence that expired EAIs may still contain significant doses of available epinephrine have motivated interest in the efficacy of expired EAIs as treatments of last resort. Degradation of expired EAIs, which can be caused by improper storage conditions, results in various degrees of discoloration of the epinephrine solution. Previous studies have determined that significant epinephrine remains available in expired EAIs, but these have only considered EAIs that show no discoloration. Here, we investigate the potential for colorimetric estimation of available epinephrine dose based on the degree of discoloration in expired EAIs. The correlation of available epinephrine dose and time since expiration date was poor (r = - 0.37), as determined by an industry standard UHPLC protocol. Visible absorbance of the samples integrated across the range 430-475 nm correlated well with available epinephrine dose (r = - 0.71). This wavelength corresponds to the blue channel of a typical smartphone camera Bayer filter. Smartphone camera images of the EAI solutions in various illumination conditions were analyzed to assign color indices representing the degree of discoloration. Color index of the samples showed similar correlation (|r| > 0.7) with available epinephrine dose as that of visible spectrophotometry. Smartphone imaging colorimetry is proposed as a potential point-of-use epinephrine dose estimator for expired and degraded EAIs. Graphical abstract.

Purpose: Health care professionals can be exposed to hazardous drugs such as cytostatics during preparation of drugs for administration. Closed sytem transfer devices (CSTDs) were introduced to provide protection for healthcare professional against unintended exposure to hazardous drugs. The interest in CSTDs has significantly increased after USP <800> monograph was issued. The majority of the studies published so far on CSTDs have focused on their "containment" function. However, other important attributes for CSTDs with potential importance for product quality impact are not yet fully evaluated., Methods: In the current study, we evaluated four sytems from different suppliers, in combination with different container closure systems (CCS), using solutions of different viscosity and surface tension. The different CSTD / CCS combinations were tested for (a) containment (integrity) using a highly sensitive helium leak test, (b) the force required for mounting the vial adaptor, (c) contribution to visible and subvisible particles as well as (d) the hold-up volume., Results: Results show that the majority of CSTDs may have leaks varying in size, and that some of them generated visible particles due to stopper coring and subvisible particles, both due to silicon oil and particulate contaminations of the Devices. Finally, the holdup volume was up to 1 mL depending on the CSTD type, vial size and solution viscosity., Conclusion: These results show that there is a need to evaluate the compatibility of CSTD systems to select the best system for the intended use and that CSTDs may adversely impact product quality and delivered dose.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs., Methods: In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017., Results: All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter., Conclusion: Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements., Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD., Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices., Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Accuracy in patch testing is critical for correct allergen identification. This multistep process is prone to error and risk increases with more staff (physicians, residents, fellows, technicians), antigens, and patients. Standardized safety checkpoints increase efficiency, consistency, and safety. In this article, we outline workflows developed for 20 years of experience, which maximize productivity and communication among team members to minimize system errors. We organize patch safety into 5 key "hurdles," or steps, and outline the specific safety procedures of each step via the use of checklists, easy visual cues, and double verification. The 5 hurdles include the following: (a) inventory (stocking sufficient antigens, maintaining chemical viability through appropriate storage, systematizing correct antigen identification); (b) patch preparation (consistent order communication, standardizing conformation and numbering of patches, accurate placement of antigens on patches); (c) application (maximizing patch contact with suitable skin on patient, minimizing risk of interference with patch test reactions); (d) documentation (accurate maps, avoiding "frame shift" misreads); and (e) education (promoting patient partnership, allergen avoidance).

Background and Objective: Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottles at 5°C ± 3 °C., Method: Five bottles of infusion were stored at 5°C ± 3 °C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at three wavelengths were measured. The concentrations were measured by ultra-high performance liquid chromatography - diode array detection., Results: Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42nd day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase in the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength. The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. The stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days., Conclusion: Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottles at 5°C ± 3 °C and could be prepared in advance with these storage conditions., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes., Methods: A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at -20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure., Results: Stability was successfully maintained for every concentration and container tested when stored at -20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature., Conclusions: Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Various jurisdictions have legalized cannabis for medical purposes. As with all psychoactive medications, medical cannabis carries a risk of diversion and accidental ingestion. These risks may be particularly high among long-term medical cannabis patients as safety practices may become less salient to patients once the treatment becomes part of everyday life. The current study examines whether patients who have used medical cannabis for longer periods differ from those who have used for shorter periods in terms of sociodemographic background and other key aspects of medical cannabis use. Furthermore, the study examines the relationship between length of medical cannabis treatment and risk factors related to storage and diversion. Finally, the study examines the extent to which oncologists provide information to their patients about safe storage and disposal., Methods: One hundred twenty-one medical cannabis oncology patients were interviewed face-to-face and 55 oncologists participated in a survey about safe storage and disposal practices related to medical cannabis., Results: Length of medical cannabis treatment was related to administration by smoking and using higher monthly dosages. In terms of risk for unsafe storage and diversion, length of medical cannabis was positively associated with using cannabis outside the home and having been asked to give away medical cannabis. Physicians did not report providing information to patients regarding safe storage and disposal practices in a regular manner., Significance of Results: Results suggest that there is an ongoing risk of unsafe storage and diversion over the course of medical cannabis treatment. Oncologists may need to give more consistent and continued training in safe storage and disposal practices, especially among long-term medical cannabis patients.

Parenteral amino acid solutions containing tryptophan tend to develop a yellow colouration upon storage. Hence, the aim of the present study was to find out whether tryptophan degradation products are the reason for the yellowing. The degree of discolouration and tryptophan degradation was examined by visual examination and UV/Vis measurements with respect to oxygen presence, pH value, and duration of steam sterilization. LC-UV analyses of autoclaved tryptophan solutions indicated eight degradation products, namely R,R/R,S 2-amino-3-(oxoindolin-3-yl)propanoic acid, R,R/R,S 2-amino-3-hydroxy-2-oxoindolin-3-yl)propanoic acids, cis/trans 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid, N´-formylkynurenine, and kynurenine. The proposed degradation products were confirmed by spiking of synthesized degradation products and LC-UV/MS analyses. The LC-UV analysis method was optimized and validated according to the ICH guideline Q2 (R1). Tryptophan stability in commercially available parenteral amino acid formulations was evaluated over a storing period of 12 months in two common types of primary packaging after autoclave procedure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cold chain equipments (CCEs) at health facilities (HFs) are an essential part of the immunization supply chain (ISC). The CCEs in government HFs of Delhi were never assessed using the World Health Organization-United Nations Children's Fund (WHO-UNICEF) Effective Vaccine Management (EVM) tool except that of state vaccine store during National EVM assessment 2013., Objectives: The objective of the study was to assess the CCEs and their management in government HFs using the WHO-UNICEF EVM tool in a district of Delhi., Methods: The assessment was done during December 2017-March 2018 in one randomly selected district of Delhi. Sample size and site selection were done using the WHO EVM site selection tool. A total of 29 HFs were assessed along with District Vaccine Store. Questions on CCEs in EVM tool 1.0.9 were used for data collection., Results: Out of 56 electrical CCEs, 8.9% were nonfunctional, 48.2% were noncompliant with WHO standards, 5.4% were not chlorofluorocarbon free, 4.7% did not have temperature monitoring device, and 18.8% did not have stabilizer. Eighty-six percent of passive containers were compliant with the WHO standards. The storage capacity of electrical vaccine storage equipment was insufficient in 3.4%, passive container capacity in 65.5%, and ice packs preparation and storage capacity in 24.1% of HFs. There was no planned preventive maintenance of CCEs and no standard operating procedures for emergency event management., Conclusion: There was a shortage of vaccine storage, ice packs preparation and storage, and passive container capacity. Many CCEs used in ISC of assessed sites were noncompliant to the WHO standards. There was no PPM of CCEs and no guidelines for emergency event management., Competing Interests: None

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., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Pharmaceuticals are beneficial to humankind and emerged as crucial arms to treat/manage multiple disease pathogenesis in the present era. In analogous, these medicines/ medical devices should be used cautiously as they possess a potential threat to induce multiple undesired effects that may be related to human health or the environment. Daunting effects may arise due to the improper disposal of unused/expired medicines. Hence, to minimize such harm, there should be adequate knowledge and practice among the population regarding the safe disposal of unused/expired medicines or related pharmaceutical devices. The lack of approved information regarding safe disposal of such substances may invite serious concerns like environmental pollution, which may induce immediate health hazards to the present population and upcoming future generations. There are numerous ways to dispose of, or manage the unused and expired pharmaceutical substances. Sharing the medicines among siblings, friends, and family members are never free from serious health risks. Storing the unused and expired medicines in the home increases the risk of intentional or accidental ingestion of such substances and may create a health emergency. Disposing medicines like household and municipal waste may lead to environmental pollution and harm to humans and animals. The present review finds the multiple unsafe ways of disposal of unutilized medications/tools. Furthermore, it also summarizes the disposal pattern of unutilized medications among the few developed and undeveloped nations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The fundamental human desire is prevention from the infectious disease. Vaccine is the basic element to fulfill this human craving. The proper handling of vaccine can minimize the degradation. The main aim of this study is to find out the knowledge of respondents and storage condition and handling of marketed vaccines in different private clinics, hospitals and community pharmacies in Karachi, Pakistan. The present study revealed that ~77% have been allowed to visit their vaccine storage compartment. The cumulative knowledge of respondents regarding recommended temperature, shake test, thermal, freezing and photo degradation were 49.34%, 24.01%, 95.78%, 54.35% and 47.23% respectively. The major mishandling like the medicines, food and drinks and even laboratory specimen have been noticed 76.3%, 61.62% and 5.35% respectively. Moreover, water filled bottles on upper, lower and door shelves and ice packs or ice trays 3.43% and 14.18%, respectively, have been found in refrigerators and freezers, respectively. No expired vaccines have been found. The major consequence, in the study has been found to be mishandling by the absence of non-professional personnel. Either doctors or pharmacist (health associated professionals) as respondents were nearly all aware about the consequences of the mishandling of vaccines and have the knowledge about the recommended temperature, thermal, photo degradation, and freezing hazards of vaccines. The world-renowned immunization authorities have strongly recommended national/local immunization programs. On the basis of the present study, it is recommended to train the staff and prepare a national guideline for the storage and handling of vaccines, and forcefully implements the law to adopt the particular guideline.

The pharmacopeia method for measuring the chemical durability of parenteral glass packaging is the hydrolytic resistance test in which the vial is filled to 90% of its brimful volume as described, for example, in USP <660>. However, an increasing number of innovative drugs are filled significantly below the nominal volume of the vial. As a consequence, the determined hydrolytic resistance is not representative of the concentrations of leached "glass" elements for low fill volumes. This is attributable to two main factors: Firstly, an increasing ratio of the wetted surface to volume and secondly an increased leaching tendency typically observed with borosilicate glass of the wall near bottom area, especially when standard manufacturing technology is applied.The extent of both contributing effects has been analyzed by determining the amounts of the representative leached "glass" elements, boron, sodium, and silicon, after vial storage for 24 weeks at 40°C with different fill volumes (0.5, 1.0, and 2.0 mL). The vials which have been investigated in this study have a nominal fill volume of 2 mL, were made from Type I class B borosilicate glass (Fiolax®) and from aluminosilicate glass and were filled with either purified water or a 15% KCl solution.The standard conversion process for tubing into vials was used for Fiolax vials (standard quality vials) and for aluminosilicate vials. In addition, an optimized conversion process (delamination controlled technology) was used to create low-fill quality Fiolax vials. The vial quality obtained from the two different converting technologies greatly influenced the concentrations of leached "glass" elements measured, especially when low fill volumes were used. LAY ABSTRACT: Borosilicate glass containers, because of their chemical inertness, excellent barrier properties, high transparency, and mechanical stability, have been successfully used for decades to package parenteral drug formulations. Nevertheless, Type I glass can be altered over a period of time when in contact with the drug formulation. The result of this interaction is even more pronounced for some new innovative drugs that are delivered to the patient in small dosages significantly below the nominal storage capacity of the glass vials. When the fill volume of the vials is reduced, the contribution of the bottom area to the wetted surface increases, resulting in a higher surface-to-volume ratio. Therefore, the concentrations of leached elements will be increased and this can cause problems for sensitive medical products. This effect is not usually observed with the standard test procedures described in the pharmacopeia because the vials are filled with a high volume to 90% brimful capacity (e.g., as described in USP <660>). In this study, the leachable behaviors of vials made of borosilicate and aluminosilicate glass were evaluated by using medium and low fill volumes with storage for 24 weeks at 40°C. The standard conversion process to manufacture a vial from glass tubing introduces volatile "glass" elements into the vial wall near the bottom area. This mechanism has been described and supported by time-of-flight secondary ion mass spectrometry (TOF-SIMS) measurements of the inner vial surface as reported by Rupertus et al. The diffusion mechanism of volatile components will increase the leaching propensity of the vial, especially for low fill volumes. However, innovative manufacturing techniques are able to avoid the diffusion of volatile elements into the wall near the bottom area. This is achieved by a specific process setup in combination with a suitable monitoring test during vial production, which gives a quantitative measure of the leaching tendency of the wall near the bottom area. Borosilicate glass vials manufactured with this setup (low-fill quality vials) showed a drastic reduction in leachables, especially with low fill volumes. Vials composed of a boron-free glass showed no advantages in terms of leaching behavior when compared with borosilicate glass vials in general., (© PDA, Inc. 2019.)

Oral rehydration solutions (ORS) are specifically formulated with an osmolality to optimize fluid absorption. However, it is unclear how many ORS products comply with current World Health Organization (WHO) osmolality guidelines and the osmotic shelf-life stability is not known. Therefore, the purpose of this investigation was to examine the within and between ORS product osmolality variation in both pre-mixed and reconstituted powders. Additionally, the osmotic stability was examined over time. The osmolality of five different pre-mixed solutions and six powdered ORS products were measured. Pre-mixed solutions were stored at room temperatures and elevated temperatures (31 °C) for two months to examine osmotic shelf stability. Results demonstrated that only one pre-mixed ORS product was in compliance with the current guidelines both before and after the prolonged storage. Five of the six powdered ORS products were in compliance with minimal inter-packet variation observed within the given formulations. This investigation demonstrates that many commercially available pre-mixed ORS products do not currently adhere to the WHO recommended osmolality guidelines. Additionally, due to the presence of particular sugars and possibly other ingredients, the shelf-life stability of osmolality for certain ORS products may be questioned. These findings should be carefully considered in the design of future ORS products.

Background: Medicines are stored in most households around the world for a range of different purposes including emergency use and the treatment of acute or chronic illnesses. The presence of medicines in households is becoming a significant risk factor for irrational medicine storage, disposal, and use in developing countries due to limited information and knowledge offered on safe storage. This study examined how patients store medicines and highlighted factors which influence home storage behaviours for medicines in China., Method: A cross-sectional survey of 625 households was undertaken. In each household, data were collected from the head of household present at home. The study covered six provinces in China including the North, Central, and Southern regions. Respondents were interviewed by doctors. The doctors were study assistants and data collectors. "Attention" was taken as the research focus and a five-point Likert scale was used to measure attitudes to medicine storage at home. Factor analysis, variance analysis, and the multivariable logistic regression models were employed in the present study., Results: Of the households investigated in this study, cold medications were the medicine most commonly stored at home. The majority of the respondents gave more attention to the expiration date of medicines compared to other factors. Only a few respondents thought humidity was important factor influencing home storage of medicines. Despite some attention being given to the location of storage for home medicines, considerably more information is needed to improve awareness. In addition, our data revealed that some attention had been paid to elimination and recycling mechanisms but similarly, increased awareness is needed. There were obvious differences between the populations used in the study, due to differences in socio-demographic characteristics of the study participants. Age is the most important factor influencing the attention paid to home storage of medicines in China., Conclusion: A major improvement in the awareness of correct storage conditions of medicines for home use can be realized by increased education, and highlighting the importance of correct medicine storage, disposal methods and usages, which has high potential to deliver public health benefits in China. Some suggestions were provided to health care providers.

During the manufacture of a monoclonal antibody drug product, which was aseptically filled within a vapor phase hydrogen peroxide-sanitized isolator, samples were taken to investigate the hydrogen peroxide uptake behaviors. Surprisingly, the samples had no detectable hydrogen peroxide (most results below the limit of detection). This finding was later attributed to hydrogen peroxide decomposition after the samples were stored frozen at -20°C for two weeks before testing. This case study highlights the criticality of storage conditions for hydrogen peroxide-containing samples and summarizes an investigation on hydrogen peroxide stability in water and in three monoclonal antibody solutions having a wide protein concentration range (30-200 mg/mL). Samples were stored at three temperatures (-70°C, -20°C, or 2-8°C) for up to 28 days to assess the impact of protein concentration and storage temperature on hydrogen peroxide decomposition rates. Hydrogen peroxide degraded slightly more rapidly with increasing protein concentration independent of storage condition. When stored at -20°C, hydrogen peroxide was least stable and degraded faster than when stored at 2-8°C. Hydrogen peroxide was most stable when the samples were stored at -70°C. Overall, this case study brings the hydrogen peroxide stability issue to the attention of process development scientists and engineers and offers a valuable lesson learned during process development. LAY ABSTRACT: The use of vapor phase hydrogen peroxide as a sanitizing agent for isolator and cleanroom decontamination has become common in recent years. Because of the potential impact of residual hydrogen peroxide on biopharmaceutical product quality, hydrogen peroxide uptake behaviors and mechanisms during the manufacturing process within these barriers need to be evaluated and understood. Samples taken from various small-scale and manufacturing-scale hydrogen peroxide uptake studies are often stored frozen before testing. This case study reports an important and interesting finding about hydrogen peroxide stability in samples collected for hydrogen peroxide uptake investigation, and it demonstrates the relationship between hydrogen peroxide stability and storage temperature, storage duration, and monoclonal antibody concentration. The approach and outcome of this study are expected to benefit scientists and engineers who develop biologic product manufacturing processes by providing a better understanding of drug product process challenges and appropriate sample storage., (© PDA, Inc. 2019.)

Background: Emerging research on surgeons and the opioid epidemic have focused on the adult population. Consequently, little is known regarding opioid-prescribing practices in the pediatric population. The goal of this study is to examine postoperative opioid-prescribing and consumption patterns, as well as storage and disposal trends for specific pediatric urologic procedures., Study Design: Patients undergoing surgery associated with specified Current Procedural Terminology codes were retrospectively identified, and details regarding opioid medications were obtained through our pharmacy database. Patients' guardians were contacted two weeks postoperatively to determine opioid usage. Opioids were prescribed at a standard dosing of 0.1 mg/kg per dose or the equivalent., Results: Of the 171 identified patients, 117 patients were successfully contacted, with 67 (39%) completing telephone surveys. The 3 most common pediatric urology procedures were inguinal hernia repair (N = 39), circumcision (N = 27), and cystoscopy (N = 16). Across all procedures, there was an average excess of 9.8 doses prescribed, corresponding to an overprescription rate of 64%. Of the patients prescribed opioids, 41 (62%) had leftover opioid medication two weeks postoperatively. Thirty-two of 41 (78%) patients did not dispose of their leftover medication. Only 13 patients received perioperative counseling on appropriate storage and disposal of opiates., Discussion: Prescribing practices for an array of pediatric urologic procedures are non-standardized and often generously excessive. We show universal overprescribing for all our reviewed urologic procedures. Sixty-two percent of pediatric urology patients did not use their entire prescribed opiate, leaving a significant pool of medicine within the pediatric family home. Given the low incidence of perioperative education, unsurprisingly a majority of our patients improperly handled and disposed off excess opioid medication., Conclusion: There is general overprescription of postoperative opioids and poor perioperative opioid education in the pediatric urology population., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource- and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H 2 O 2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

During the past years, there has been an increasing focus on the presence of silicone oil as a contaminant in pharmaceutical formulations kept in prefilled syringes (PFSs). As the PFSs are coated on the inner wall with silicone oil (polydimethylsiloxane), there is a potential risk that the oil can migrate from the inner surface of the primary packing material into the aqueous solution. Several studies have demonstrated that presence of silicone oil as droplets in a high-concentrated protein formulation can cause protein aggregation. Hence, because the use of silicone-coated primary packing material for protein formulations are increasing, the call for an easy and quantitative method for determination of silicone oil and its degradation products in pharmaceutical formulations is therefore needed. Several analytical techniques have in the past been developed with the aim of detecting the presence of silicone oil and degradation products hereof. Most of these methods require hydrolyzation, derivatization, and extraction steps followed by, for example, gas chromatography-mass spectrometry analysis. Applying these methods can cause a loss in detection or an overestimation of the hydrolytic degradation products of silicone oil, that is, trimethylsilanol and dimethylsilanediol. The 2 silanols are highly hydrophilic and prefers the aqueous environment. Analysis of an aqueous formulation obtained from a PFS by 1 H-NMR spectroscopy provides data about the content and levels of silicone oil and the 2 silanols even in levels below 10 ppm. The 1 H-NMR method offers an easy and direct, quantitative measurement of samples intended for clinical use and samples kept at elevated temperature for a prolonged time (i.e., stability studies). The result of the study presented here showed dimethylsilanediol to be the main silicone compound present in the aqueous formulation when kept in baked-on PFSs. The degradation product dimethylsilanediol, in full accordance with expected hydrolytic degradation of silicone oil, increased during storage and with elevated temperature. In addition, the method can be applied to aqueous samples where polydimethylsiloxane has been added as, for example, the major constituent of antifoam., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: This article reviews the literature concerning ceftazidime stability and potential for toxicity from pyridine (a degradation product) in the light of decades of apparent safe use of this antibiotic when given by continuous i.v. infusion but recent changes in regulatory body/manufacturer advise a need to change infusion devices more frequently., Summary: In the outpatient setting, ceftazidime is ideally administered by continuous i.v. infusion because of its short half-life and lack of post-antibiotic effect. While continuous i.v. infusion provides the optimal pharmacokinetic/pharmacodynamic profile, the frequency with which infusion devices need to be changed is critical to the practicality in the outpatient setting, especially where trained staff are required to visit the patient in their home to change the device. The rate of ceftazidime degradation (and pyridine formation) is temperature, concentration, and solvent dependent. By using the lowest effective dose (guided by pathogen minimum inhibitory concentration [MIC] so as to achieve a blood concentration ≥ 4 × MIC over the whole dosage interval), keeping ceftazidime concentration ≤ 3%, using 0.9% sodium chloride injection as diluent and maintaining temperature between 15-25°C when connected to the patient, the amount of pyridine formed over a 24-hour period can be minimized and toxicity prevented. When pathogen MIC dictates that > 6 g ceftazidime/day is required, alternative antibiotics should be considered and/or greater attention paid to temperature and concentration of the infusion solution., Conclusion: Ceftazidime can be used safely and effectively via continuous i.v. infusion in the outpatient setting with once-daily changes of infusion device provided the concentration and temperature of the infusion solution is controlled. In this way, more frequent changes of infusion device (that increase the risk of blood-borne infection and reduce the practicality of continuous i.v. infusion in the home) can be avoided.