Background: Dyspnea is the most common symptom associated with the COVID-19 caused by novel coronavirus SARS-CoV-2. The aim of this study was to assess the prevalence of dyspnea, observe co-variables, and find predictors of dyspnea after two months of recovery from COVID-19. Methods: This study was conducted in 327 patients and they were asked if they had experienced dyspnea with the COVID-19. Patients’ responses about dyspnea were categorized as being improved, remained the same, or (worsened) two months post-COVID-19. Software “R” was used in this study for statistical computing. The p-value was set <0.05 for all statistical tests. A repeated k-fold cross-validation was used for measuring the accuracy of logistic regression. Results: Of the total 327 participants in the study, 34% had stated that they were suffering from respiratory symptoms even after two months of COVID-19. The study demonstrated that SpO2 (p value <0.03), D-dimer (p value <0.001), serum ferritin (p value <0.006) and the presence of dyspnea are significantly correlated. The repeated k-fold cross-validation method revealed that the prediction performance was around 65%. Conclusion: These findings can be useful for the physicians treating COVID-19 patients after discharge from hospital.
Objective: The purpose of this study was to evaluate the chemical stability of previously dispensed, expired naloxone products.Setting: When properly stored, certain products maintain stable, defined as within compendia acceptability, beyond their manufacturer's expiration date. Stockpiling life-saving medications such as the opioid overdose reversing agent naloxone nasal spray (NNS) or injection (NIJ) is of utmost importance to ensure public health emergency preparedness and response.Design/interventions/methods: After each naloxone product was stored at room temperature for several months (6-19) past their labeled expiration date, the level of active therapeutic content and the presence of degradation impurity, 2,29-bisnaloxone, were evaluated via chromatographic separation with waters higher performance liquid chromatography integrated using the Waters X-Select CSHC-18. The effluent was detected at 229 nm.Main outcome measure: Active naloxone presence and the presence of degradation impurity, 2,29-bisnaloxone, were evaluated.Results: The mean potency of naloxone in both NNS and NIJ, up to 10 and 19 months post-expiration, respectively, is within the 90-110 percent United States Pharmacopeia acceptance limit (NNS: 102.8 ± 2.6 percent and NIJ: 106.0 ± 1.3 percent). No impurity was detected in any chromatogram of the expired products.Conclusion: In summary, since both NNS and NIJ were found to be chemically stable beyond 10 months of the expiration date, shelf-life extension of climate controlled, commercially available naloxone products should be further investigated as a potential cost savings measure for national strategic stockpiles, emergency medical services, hospitals, and public responders.
Abstract Background and aims Dyspnea is one of the most common symptoms associated with the COVID‐19 caused by novel coronavirus SARS‐CoV‐2. This study aimed to assess the prevalence of dyspnea, observe co‐variables, and find predictors of dyspnea after 2 months of recovery from COVID‐19. Methods A total of 377 patients were included in the study based on their responses and clinical findings during initial admission to the hospital with COVID‐19. After excluding five deceased patients, a total of 327 patients were interviewed through telephone using a 12‐point dyspnea scale and using relevant questions to gauge the patient clinically. Interviews were carried out by trained physicians, and responses were recorded and stored. All analyses were carried out using the statistical programming language R. Results Of the total 327 participants in the study, 34% had stated that they were suffering from respiratory symptoms even after 2 months of COVID‐19. The study demonstrated that patient oxygen saturation level SpO2 (P = .03), D‐dimer (P = .001), serum ferritin (P = .006), and the presence and severity of dyspnea are significantly correlated. In addition to that, patient smoking history (P = .012) and comorbidities such as chronic obstructive pulmonary disease (COPD) (P = .021) were found to be statistically significant among groups. Conclusion These findings of this study can be useful for predicting and managing long‐term complications of COVID‐19.
Quality assurance is a key element in the process of creating safe and effective preparations. Furthermore, the implementation of quality-assurance measures allows 503A pharmacies to ensure accurate, well-made preparations to their customers. When corrective and preventive measures are not implemented, the risk of errors is increased, like subtherapeutic or supratherapeutic compounded medications. The objective of this article was to demonstrate the importance of quality assurance through the development and validation of the compounding method, preparation characterization, training, implementation of a master formulation record, compounding protocol, and verification to prevent compounding errors. Two groups, comprising of 10 students, compounded lidocaine gel following the quality-assurance guidelines in accordance with United States Pharmacopeia Chapter <1163>. Following the trial, the preparations from both groups were tested to evaluate the content of lidocaine using high-performance liquid chromatography and an ultra-viscosity detector. The study results indicated that the newly developed, validated procedure produced a stable, uniform, highly reproducible (%Assay ± SD; 101.65% ± 1.04), and elegant (clear hydro-alcoholic gel) preparation with a high yield (~98.5%). There was no significant difference observed in the %Assay results obtained from the two groups (%Assay ±SD; P1: 98.76% ±1.01, and P2: 99.02% ±1.39, %Difference: 0.3). Overall, our findings suggest that the implementation of quality assurance could significantly reduce compounding errors and improve both preparation quality and patient safety.
The art and the skill set of compounding fulfill the important need of tailor-made pharmaceuticals for use by both institutions and individual patients. Over the last 20 years, there have been more than 200 adverse events involving compounded products; infections, poisonings, contaminations, and dosing inaccuracies have been problematic. The probability of a correlation between the lack of institutional training and number of serious events could be significant. This survey was an endeavor at fundamental cause analysis and proactive management in relation to the PharmD Curricula as a means of error prevention. A questionnaire was sent to the pharmacy school faculty (department chairs, dean/assistant deans, and pharmaceutical science faculty) across the country. The survey responses were received from 78 participants. The questionnaire evaluated the respondent's overall knowledge and approach toward the subject in their curriculum. The survey results show 38.9% faculty agree that their college's curricula lacks sufficient training in microbiological testing, and 16.7% faculty agree their college does not provide sufficient training in nonsterile and sterile compounding (as per United States Pharmacopeia Chapters <795> and <797>). A majority of faculty agree on the implementation of quality assurance in compounding courses (as per United States Pharmacopeia Chapter <1163>) as either an elective (62.5%) or mandatory class (43.3%), and most of the participants (85.1%) think there is a need to teach quality assurance as continuing education to practicing pharmacists. The survey data suggest a general desire for enhancement of compounding course curriculum, which could reduce the number of adverse events related to compounding. The data also suggests a necessity for the implementation of continuing education programs for practicing pharmacists and academic faculty across the country.
Misbranded and counterfeit dietary supplements have been an issue on which the US Food and Drug Administration has been vigilantly regulating.The ubiquity of online-shoppable weight-loss supplements and their unrestricted consumption by people with obesity are serious matters of concern.Fucoxanthin, a brown-seaweed-extracted carotenoid has exhibited anti-obesity property in some clinical trials through its ability to over express uncoupling protein (UCP1) in the white adipose tissue, which leads to fat burning.However, since the clinical trials apply pure fucoxanthin instead of fucoxanthin-bearing dietary supplements, a critical analysis is warranted to quantify fucoxanthin in brown seaweeds to validate their rationale in weight loss mechanism.This study examined ten randomly chosen online-sourced brands of fucoxanthin-containing dietary supplements and analyse the content using High-Performance Liquid Chromatography (HPLC) equipped with UV-Vis and photodiode array detector.Our exploration revealed that, of these 10 products, 3 (30%) did not have any detectable quantity of fucoxanthin, 5 (50%) contained a only a trace amount of it, ranging from 0.001-0.01mg per capsule, and only 2 (20%) products contained 0.4 mg or 2 mg of fucoxanthin, meeting their label claim.This worrying finding may be interpreted that the existing ease-of-access and pervasive nature of online-sourced dietary supplements require more stringent regulatory screening.
Compounding perfection confirms a safe, swift, and efficacious delivery of personalized compounded medication. A large variability of the potency of the finished product may stem from complicated formulation or difficult-to-adopt methods. Also, the formulation and compounding method may adversely affect the amount of time needed to finish the compounding and dispense the medication for the patient. This study involves the development of a novel formulation and compounding method of lidocaine hydrochloride 2% dental gel and compares it with an older, more common formulation which contains five times more alcohol and four times more gelling material. Student-pharmacists were recruited in this study, and the finished products were compared in terms of their intra-group potency uniformity, time needed to finish the compounding, and post-compounding psychometric feedback by the compounders. Each compounder participated in both of the formulation methods in a crossover fashion. Our result indicates that the new formulation and the associated method enables the compounders to produce products with less variation, requiring statistically significantly less compounding time and better acceptability by the compounder.
Mushrooms have been used as part of the average diet and as a nutraceutical for thousands of years due to their immense health benefits. The purpose of this study was to develop a simple, fast, accurate, specific, reproducible, and robust chromatographic method to identify and quantify two water-soluble vitamins: thiamine (B1) and riboflavin (B2) in mushrooms. The method employed for qualitative and quantitative analysis of these vitamins was Reversed Phase-High Performance Liquid Chromatography (RP-HPLC) equipped with Ultraviolet–Visible (UV-Vis) Detector. The extraction process involved acid hydrolysis followed by enzymatic dephosphorylation with takadiastase enzyme. Chromatographic separation was achieved with a Shimadzu prominence HPLC system using isocratic elution mode on a Waters Xterra® MS C-18 column (4.6mm × 150mm, 5 μm) integrated with a XBridge® BEH C-18 Guard column (2.1mm × 5 mm, 5 μm). The mobile phase of this study consisted of buffer and methanol in the ratio of 80:20, where the buffer contained sodium-1-hexanesulfonate, glacial acetic acid, methanol, and pH adjusted to 3.0 with diethylamine. Vitamins were detected simultaneously at their lambda max wavelengths B1: 245nm and B2: 268nm using dual-wavelength UV detection technique to get their highest response. The proposed method was found to be specific, linear R>1.0, accurate, precise (% recovery ± SD; B1:104.45±4.5 and B2: 104.88±2.04), sensitive, (limit of detection for B1 and B2 was 0.043 and 0.029 μg/mL, respectively), and robust for mushrooms analysis. No coeluting peaks were observed at the retention time of the vitamins and all the peaks were spectrally homogenous. The standard and sample solutions were found to remain stable at cold temperature for 72 hours. In summary, our data suggest that the proposed method could be used in food industries to monitor the product quality during routine quality control purposes.
Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. In the final analysis, this investigation concluded that the S-octylthio derivative is a more effective growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more favorable cytotoxic and metabolic parameters over disulfiram.
ABSTRACT Praziquantel (PZQ) is the only drug available for the treatment of schistosomiasis, and since its large-scale use might be associated with the onset of resistance, new antischistosomal drugs should be developed. A series of 26 synthetic tetraazamacrocyclic derivatives and their metal complexes were synthesized, characterized, and screened for antischistosomal activity by application of a phased screening program. The compounds were first screened against newly transformed schistosomula (NTS) of harvested Schistosoma mansoni cercariae, then against adult worms, and finally, in vivo using the mouse model of S. mansoni infection. At a concentration of 33 μM, incubation with a total of 12 compounds resulted in the mortality of NTS at the 62% to 100% level. Five of these showing 100% inhibition of viability of NTS at 10 μM were selected for further screening for determination of the 50 inhibitory concentrations (IC 50 s) against both NTS and adult worms. Against NTS, all 5 compounds showed IC 50 s comparable to the IC 50 of the standard drug, PZQ (0.87 to 9.65 μM for the 5 compounds versus 2.20 μM for PZQ). Three of these, which are the bisquinoline derivative of cyclen and its Fe 2+ and Mn 2+ complexes, showed micromolar IC 50 s (1.62 μM, 1.34 μM, and 4.12 μM, respectively, versus 0.10 μM for PZQ) against adult worms. In vivo , the worm burden reductions were 12.3%, 88.4%, and 74.5%, respectively, at a single oral dose of 400 mg/kg of body weight. The Fe 2+ complex exhibited activity in vivo comparable to that of PZQ, pointing to the discovery of a novel drug lead for schistosomiasis.
The purpose of this study was to evaluate physicochemical properties of an antimalarial drug lead, 4,10-bis(7- chloroquinoline)-1,4,7,10-tetraazacyclododecane (Cyclenbisquinoline; CNBQ) and its hydrochloride salt. The free base (FB) of CNBQ is a white polymorphic crystalline powder and the salt is off-white powder. The application of standard experimental protocol including differential scanning calorimetric (DSC) analyses revealed that the FB has at least four different crystalline polymorphs melting at 166°C, 178°C, 195°C and 234°C, respectively, and the salt showed a broad endotherm, suggesting it to be amorphous in nature. Equilibrium solubility and stability of both FB and salt were carried out in different mediums, and samples were analyzed using reverse phase-high performance liquid chromatography (RP-HPLC). The compound is highly hydrophobic; however, salt formation improved its water solubility by approximately 370-fold. Both FB and salt forms were stable in a wide range of conditions (acid, base, water, light and heat), except oxidation. All these properties, in addition to previously determined and published log P and pKa values would be useful in implementing the modern quality by design (QbD) approaches for further development of the drug lead.
The purpose of this experiment was to evaluate and compare the pKa values of the poorly water soluble, weakly basic, novel antimalarial drug lead, 4,10-bis (7-chloroquinoline)-1,4,7,10-tetraazacyclododecane (CNBQ). Three separate methods, pH-metric, UV-metric, and Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), were employed to determine the pKa values between 2.0-12.0 pH range. The acetate and phosphate buffers, in addition to methanol and acetonitrile as co-solvents and potassium chloride to maintain the ionic strength, were used as appropriate. In UV-metric method, the drug substance is dissolved in aqueous media eliminating any interference of a co-solvent for measuring the pKa. Consequently, the pKa values obtained by the UV-metric method are considered accurate, as opposed to potentiometric and RP-HPLC methods that require the use of co-solvents. Thus, through the utilization of UV-metric method three pKa values, 5.9, 6.6, and 8.7, were obtained for CNBQ. These studies would be useful to determine the pKa values of the related drug leads under development.