Acetaminophen In Formulations Research Articles

Costs and outcomes associated with the administration of Intravenous Acetaminophen in neonates after esophageal atresia and tracheoesophageal fistula repair

BackgroundOver the last decade, the intravenous (IV) formulation of acetaminophen (APAP) has gained popularity as a safe and effective first-line analgesic in the neonatal intensive care unit and it is especially useful in peri-operative settings where oral agents are contraindicated. The primary objective was to examine the outcomes and costs associated with the use of IV APAP in combination with opioids versus opioids alone as a pain management strategy after neonatal esophageal atresia (EA) and tracheoesophageal fistula (TEF) repair. MethodsData from the Pediatric Health Information System was used to examine 1137 hospitalizations for EA/TEF repair from October 2015 to September 2018. Neonates administered opioids only, or IV APAP in combination with opioids as pain management, were included. ResultsNeonates receiving IV APAP experienced a longer median LOS, but a significantly lower mortality rate, a decreased mean daily cost, and reduced opioid use compared to neonates given only opioids. The two groups had no significant differences in pharmacy and total costs. ConclusionOur findings suggest that the use of IV APAP alongside opioids in EA/TEF repair is associated with reduced mortality and opioid use, as well as longer LOS.

Actual Access and Usage of Antipyretic Analgesics before and after COVID-19 Vaccination: Pharmacist's Roles in Promoting Proper Use of Medicines during the Infodemic

An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.

A novel composite electrode based on graphene oxide/MnO2:h‐MoO3 particles for square wave voltammetric determination of acetaminophen

AbstractA novel composite electrode was developed based on graphene oxide (GO)/MnO2:h‐MoO3 nanocomposite for sensitive and selective voltammetric detection of acetaminophen (ACP). The composite electrode materials were characterized using X‐Ray photoelectron spectroscopy (XPS), X‐Ray Diffraction (XRD), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetric (CV) techniques. In the optimum conditions, the oxidation peak current (Ipa) of ACP was increased linearly with its concentration over two linear ranges from 0.06 to 10.0 μmol L−1 and 20.0 to 80.0 μmol L−1 with a detection limit of 0.0133 μmol L−1. Due to its higher selectivity and long term stability, the composite electrode was applied to the detection of ACP in pharmaceutical formulations.

Mechanistic modeling of twin screw wet granulation for pharmaceutical formulations: Calibration, sensitivity analysis, and model-driven workflow

Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in pharmaceutical manufacturing. In this study, a mechanistic-based population balance model is applied to twin screw wet granulation. This model incorporated a recently developed breakage kernel specifically designed for twin screw granulation, along with nucleation, layering, and consolidation. Calibration and validation were performed on Hydrochlorothiazide and Acetaminophen formulations, which exhibit different particle size and wettability characteristics. Utilizing a compartmental experimental dataset, a comprehensive global sensitivity analysis identified critical inputs impacting quality attributes. The study revealed that the nucleation rate process model, effectively represented particle size distributions for both formulations. Adjustments to nucleation and breakage rate parameters, influenced by material properties and screw configuration, improved the model’s accuracy. A model-driven workflow was proposed, offering step-by-step guidelines and facilitating PBM model usage, providing essential details for future active pharmaceutical ingredient (API) formulations.

Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study

Objectives To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators. Methods This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale. Findings FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported. Conclusions This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg. ClinicalTrials.gov Identifier NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403

Analgesic onset and efficacy of a fast-acting formulation of acetaminophen in a postoperative dental impaction pain model

Objectives Speed of onset can be critical to an analgesic’s efficacy treating acute pain. To enhance onset, a new oral acetaminophen formulation intended to be fast acting was developed. Two studies evaluated the analgesic onset, efficacy, and safety of this fast-acting acetaminophen (FA-acetaminophen) tablet relative to commercial acetaminophen caplets (ES-acetaminophen) and commercial ibuprofen liquid-filled gelatin capsules (LG-ibuprofen). Methods Two single-center, single-dose, inpatient, randomized, double-blind, triple-dummy, placebo-controlled, parallel group design clinical trials were conducted using the postoperative dental impaction pain model. Subjects were healthy men and women aged 17–50 years experiencing moderate-to-severe pain after surgical extraction of at least three impacted third molars. In both studies, four treatment groups were evaluated: 1,000 mg acetaminophen as two 500 mg FA-acetaminophen tablets, 1,000 mg as two 500 mg ES-acetaminophen caplets, 400 mg ibuprofen as two 200 mg LG-ibuprofen capsules, and placebo. To maintain blinding, each subject received six units of study medication. Times to confirmed perceptible pain relief (TCPR) and meaningful pain relief (TMPR) were obtained using the double-stopwatch method. Pain intensity and relief were measured over 6 h following drug administration using a 0–10 numerical rating scale. Time to use of rescue medication (naproxen sodium) and subject global evaluations of study medications at 6 h were collected. Pharmacokinetic blood sampling and safety assessments were performed. Results Studies 1 and 2 enrolled 240 and 420 subjects, respectively. No clinically important differences among treatment groups were observed for any demographic or baseline characteristics. Efficacy results showed all active treatments statistically superior to placebo. In Study 1, TCPR was statistically significantly shorter for FA-acetaminophen compared to ES-acetaminophen and LG-ibuprofen. In Study 2, no statistically significant differences in TCPR were noted across the active treatment groups. In Study 1, FA-acetaminophen 1,000 mg provided significantly shorter TMPR compared with LG-ibuprofen but not compared with ES-acetaminophen. In Study 2, no significant differences in TMPR were noted across the active treatment groups. In both Study 1 and 2 at 15 min after administration of study drug, PID and PAR scores were greater for FA-acetaminophen than LG-ibuprofen. Conclusions Both studies suggested FA-acetaminophen had faster onset of action compared to ES-acetaminophen and LG-Ibuprofen. In light of the difference in TCPR and TMPR results between Study 1 and 2, an additional study is needed to further investigate time to analgesic onset of FA-acetaminophen compared with ES-acetaminophen and LG-Ibuprofen. Study registry numbers Study 1: NCT02735122; Study 2: NCT03224403

Sonochemical synthesis of lanthanum ferrite nanoparticle-decorated carbon nanotubes for simultaneous electrochemical determination of acetaminophen and dopamine.

A new nanocomposite consisting of lanthanum ferrite nanoparticles (LaFeO3 NPs) integrated with carbon nanotubes (CNTs) was fabricated via facile sonochemical approach. The engineered nanocomposite was applied to simultaneously determine acetaminophen (ACP) and dopamine (DA) in a binary mixture. The LaFeO3 NPs@CNT probe possesses several advantages such as superior conductivity, large surface area, and more active sites, improving its electrocatalytic activity towards ACP and DA. Under optimized conditions, the anodic peak currents (Ipa) linearly increased with increasing concentration of ACP and DA in the range 0.069-210 µM and 0.15-210 µM, respectively. The sensitivity of LaFeO3 NPs@CNTs/glassy carbon electrode (GCE) for detecting ACP and DA is 7.456 and 5.980 μA·μM-1·cm-2, respectively. The detection limits (S/N = 3) for ACP and DA are 0.02 μM and 0.05 μM, respectively. Advantages of LaFeO3 NPs@CNTs/GCE for the detection of ACP and DA include wide linear ranges, low-detection limits, good selectivity, and long-term stability. The as-fabricated electrode was applied to determine ACP and DA in pharmaceutical formulations and human serum samples with recoveries ranging from 97.7 to 103.3% and an RSD that did not exceed 3.7%, confirming the suitability of the proposed sensor for the determination of ACP and DA in real samples. This study not only presents promising opportunities for enhancing the sensitivity and stability of electrochemical sensors used in the detection of bioanalytes but also significantly contributes to the progress of unique and comprehensive biochemical detection methodologies.

Population pharmacokinetic analysis of acetaminophen overdose with immediate release, extended release and modified release formulations

Objectives The introduction of delayed release formulations of acetaminophen (APAP) has created concern about the role of formulation in overdose. We examined the APAP overdose pharmacokinetic (PK) profiles to assess the role of dose, coingestants and formulation: immediate release (IR), extended release (ER), and modified release (MR) on APAP pharmacokinetic measures. Methods We collected by-subject APAP PK data: subject description, timed blood APAP concentrations, dose, and coingestants. We sought both overdose and randomized controlled trials (RCTs) for supratherapeutic doses involving ER or MR formulations. Data analysis and simulation used the non-linear mixed-effects modeling program NONMEM-version 7.4. Results The final dataset comprised 3,033 [APAP] from 356 subjects and 15 sources including 3 RCTs (179 subjects receiving IR, 122 ER, 65 MR). The final population PK (PopPK) model was a linear 2-compartment model with first-order (oral) absorption. Covariate relationships included: APAP absorption rate and bioavailability decreased with increased oral dose (p < 0.00005) for all 3 formulations (MR > ER > IR). Post hoc analyses showed opioid coingestant increased exposure (area under the curve, AUC) by factor of 1.6. Simulations of 100 g vs 10 g doses for IR, ER and MR showed overdose of the ER formulation exhibits slower absorption and lower C max, overall exposure (AUC) is less than 80% of an equivalent dose of IR acetaminophen. The overall exposure for the MR formulation is less than 70% of an equivalent dose of IR. Conclusions Acetaminophen ER and MR formulations have slower absorption and decreased bioavailability leading to a lower C max and later T max than the IR formulation. These results have potential clinical implications because delayed absorption could confound use of the Rumack-Matthew nomogram by underestimating the severity of ingestion early in the course of treatment.

Discrimination of Substandard and Falsified Formulations from Genuine Pharmaceuticals Using NIR Spectra and Machine Learning.

Near-infrared (NIR) spectroscopy is a promising technique for field identification of substandard and falsified drugs because it is portable, rapid, nondestructive, and can differentiate many formulated pharmaceutical products. Portable NIR spectrometers rely heavily on chemometric analyses based on libraries of NIR spectra from authentic pharmaceutical samples. However, it is difficult to build comprehensive product libraries in many low- and middle-income countries due to the large numbers of manufacturers who supply these markets, frequent unreported changes in materials sourcing and product formulation by the manufacturers, and general lack of cooperation in providing authentic samples. In this work, we show that a simple library of lab-formulated binary mixtures of an active pharmaceutical ingredient (API) with two diluents gave good performance on field screening tasks, such as discriminating substandard and falsified formulations of the API. Six data analysis models, including principal component analysis and support-vector machine classification and regression methods and convolutional neural networks, were trained on binary mixtures of acetaminophen with either lactose or ascorbic acid. While the models all performed strongly in cross-validation (on formulations similar to their training set), they individually showed poor robustness for formulations outside the training set. However, a predictive algorithm based on the six models, trained only on binary samples, accurately predicts whether the correct amount of acetaminophen is present in ternary mixtures, genuine acetaminophen formulations, adulterated acetaminophen formulations, and falsified formulations containing substitute APIs. This data analytics approach may extend the utility of NIR spectrometers for analysis of pharmaceuticals in low-resource settings.

Acetaminophen-induced hypotension in sepsis

BackgroundAcetaminophen-induced hypotension has been reported in critically ill patients; however, it remains unclear whether mannitol, present as a stabilizing compound in acetaminophen formulations, affects hemodynamic changes. The objectives of this study were to clarify the direct effect of acetaminophen on blood pressure by comparing blood pressure changes after acetaminophen and intravenous immunoglobulin (IVIG) administration, both containing mannitol, in patients with sepsis and understand the risk factors for reduced blood pressure following acetaminophen administration.MethodsThis was a retrospective cohort study. Adult patients who were diagnosed with sepsis at Nippon Medical School Hospital, and who were undergoing continuous arterial blood pressure measurement and received intravenous acetaminophen or IVIG, were included.ResultsOverall, 185 patients were included, with 92 patients in the IVIG group and 93 in the acetaminophen group. The incidence of hypotension was 36.9% in the IVIG group (34 of 92 patients) and 58.0% in the acetaminophen group (54 of 93 patients) (OR = 8.26, p = 0.004). In a propensity score-matched cohort, 80 matched patients were selected. The incidence of hypotension was 37.5% in the IVIG group (15 of 40 patients) and 67.5% in the acetaminophen group (27 of 40 patients) (OR = 7.21, p = 0.007).ConclusionsAcetaminophen induced substantially greater hypotension than IVIG in patients with sepsis, with both containing mannitol. Further studies are needed to clarify the effects on hemodynamics of mannitol contained in acetaminophen formulations.

A Review of Current Literature of Interest to the Office-Based Anesthesiologist.

A Review of Current Literature of Interest to the Office-Based Anesthesiologist.

Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

Geographic Variations in Pharmacy Services and Availability of Commonly Prescribed Pediatric Urology Medications: An Opportunity to Improve Health Equity in Washington State

To describe geographic and sociodemographic variations in operating hours and availability of medications commonly prescribed by pediatric urologists at Washington State retail pharmacies. We identified all retail pharmacies in the state. We stratified counties by population density and household income (HI) and compared differences in pharmacy operating hours and availability of 10 commonly prescribed medications. 1057/1058 pharmacies were contacted. All pharmacies had liquid formulations of oxycodone, hydrocodone, ibuprofen, acetaminophen, amoxicillin, and trimethoprim-sulfamethoxazole in stock. Liquid formulations of ciprofloxacin (10%) and oxybutynin (14.3%) were uncommonly stocked, while 92.5% of pharmacies stocked nitrofurantoin suspension, and 80.9% nitrofurantoin capsules. Statewide, 108 (10.2%) of pharmacies were closed on Saturdays and 297 (28.1%) closed on Sunday. More high (HPDC) than low population density (LPDC) (62.5% vs 0%, P < .001) and high-HI than low-HI counties (62.5% vs 0%, P=.30) had 24-hour pharmacies. A larger proportion of pharmacies were open 7-days in HPDC than LPDC (75.6% vs 56.2%, P < .0001) and in high-HI than low-HI counties (100% vs 62.5%, P=.30). The likelihood of a pharmacy being open 7 days/week was significantly higher in HPDC (vs LPDC; OR=13.2, 95% CI: 4.39-39.7) and high-HI (vs low-HI; OR=4.98, 95% CI: 2.58-9.60) counties. Most pharmacies in Washington State carry medications commonly prescribed by pediatric urologists. However, retail pharmacy operating hours are widely variable and create geographic and temporal barriers in rural and poor areas that may limit the timely administration of prescription medication. Providers should consider a patient's practical ability to fill a prescription when starting a time-sensitive medication.

4‐in‐1 Multipurpose Excipient from Musa acuminata Fruit by Alkaline‐Steeping/Retrogradation (ASR) in Acetaminophen Tablet Formulation

AbstractThe conventional approach in the tablet formulation of acetaminophen (ACM) suggests the use of five or more different excipients in a wet granulation tableting process. The use of many excipients in tablet formulation may negatively create excipient–excipient interactions, excipient–drug interactions, exaggerated product side effects, and high drug load. Cutting‐edge technology would be the use of one excipient with a quadrupled functional purpose (4‐in‐1) by direct compression tableting. In this study, a novel two‐phase process called “alkaline‐steeping/retrogradation” (ASR) is employed to obtain the desired starch polymer excipient of quadrupled functional purpose. In phase I, the biopolymer is extracted from the unripe fruits of Musa acuminata by a modified alkaline solution steeping method, while in phase II, 50% w/w of the extracted polymer is retrograded. The retrograded product is re‐mixed with the non‐retrograded 50% w/w that is left from phase I. This gives a novel 50–50% w/w blend named Musa acuminata advanced starch polymer (MAP). To authenticate the efficiency of the ASR, the physicomechanical, analytical, and drug release properties of different concentrations of MAP/ACM solid systems are characterized to ascertain the compatibility. The ASR method produces a unique semi‐hygroscopic biopolymer excipient of quadruple‐function in ACM high‐dose tablet formulation by direct compression.

Improvement of Medication Adherence and Controlled Drug Release by Optimized Acetaminophen Formulation

Acetaminophen (paracetamol, APAP) is a major component of Tylenol, Penzal Q, and Panpyrin, and is the most commonly used antipyretic analgesic in children. The conventional oral drug delivery systems of APAP are pills and tablets. However alternative drug delivery methods are desirable in case of pediatric or geriatric patients, especially for drugs like APAP that must be taken in large doses at once. Another requirement for a good drug delivery system is the rapid dissolution to ensure a rapid therapeutic action as pain reliever. In this study Acetaminophen (paracetamol, APAP) was encapsulated in a water-soluble polymer. After the preparation of the solid dispersion by encapsulating acetaminophen in polyvinylpyrroli-done, the resultant granules were used in three formulations: tablets, chewable tablets, and oral dissolving films (ODF). Solid dispersions and prepared formulations were evaluated by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffractometer (XRD), and universal tensile machine (UTM), and the release behavior was compared. As a result, it was confirmed that the oral dissolving films can be taken easily because it has the advantages of both tablet and liquid dosage form accurate dosage, easy administration, easy swallowing, and fast bioavailability. Furthermore, the drug absorption rate can be effectively increased by changing the formulation.

Delivery of acetaminophen to the central nervous system and the pharmacological effect after intranasal administration with a mucoadhesive agent and absorption enhancer

Acetaminophen, a central antipyretic and analgesic drug, is one of the most commonly used drugs among individuals of all ages throughout the world. This study pharmacokinetically and pharmacodynamically investigated the transport of acetaminophen to the central nervous system and systemic circulation after intranasal (i.n.) administration, and evaluated the potential of a transnasal acetaminophen formulation in comparison to other routes of administration. Direct transport to the brain and the pharmacological effect after the i.n. administration of acetaminophen with polyvinylpyrrolidone (PVP; a mucoadhesive agent) and poly-l-arginine (PLA; an absorption enhancer) were investigated to improve retention of the dosage solution in the olfactory epithelium region and enhance the transfer of acetaminophen to the brain. The transport of acetaminophen to the brain was rapid, and the concentration in the brain, especially the olfactory bulb, was higher after i.n. administration, resulting in a greater antipyretic effect in comparison to other routes of administration. The delivery system using PVP and PLA produced a high and prolonged antipyretic effect by enhancing the transfer of acetaminophen to the brain through suppression of the transfer to systemic circulation. Thus, this transnasal drug delivery system using PVP and PLA may be a promising method for transporting acetaminophen to the brain.

DERIVATIVES OF THE RATIO SPECTRA FOR DETERMINATION OF ACETYLSALICYLIC ACID, ACETAMINOPHEN, AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

Objective: To develop a ratio-derivative spectrophotometric method for the simultaneous quantification of acetilsalycilic acid (ASA), acetaminophen (ACE), and caffeine (CAF) in fixed-dose combination formulations. The proposed method was applied to the reference drug product Excedrin® in dissolution studies.&#x0D; Methods: The method is based on the use of the first-and second-derivatives of the ratio spectra and measurements at zero-crossing wavelengths. The dissolution profiles of ASA, ACE, and CAF were obtained following pharmacopeial conditions, USP Apparatus 2 at 100 rpm and 900 ml of water. Dissolution samples were treated with the proposed UV-derivative method and the results were compared with those obtained with a validated HPLC procedure. The dissolution efficiency was used to compare dissolution profiles (HPLC vs. UV-derivative method).&#x0D; Results: The method was linear in the range of 5-25 µg/ml of ASA, 2.5-20 µg/ml of ACE, and 1-8 µg/ml of CAF (R2&gt;0.999, *P&lt;0.05). The precision and accuracy of synthetic mixtures were within acceptable criteria (2.11-3.43% and 96.78-104.15%, respectively). Nitrocellulose filters were the best option to filter samples and stability of all drugs was adequate when standard solutions were stored at 4 °C during 24 h. No significant differences were found between dissolution profiles (*P&gt;0.05).&#x0D; Conclusion: The proposed UV-derivative method allows the simultaneous determination of ASA, ACE, and CAF in commercial formulations. The method is simple, accurate, and precise and can be used in dissolution studies. Spectrophotometric methods are of low cost and harmless to the environment and, therefore, a better alternative than chromatographic methods.

Synthesis of cobalt ferrite and simultaneous determination of ascorbic acid, acetaminophen and caffeine by voltammetric method using cobalt ferrite modified electrode

In the present article, the synthesis of spherical hollow cobalt ferrite and application as an electrode modifier were demonstrated. The synthesis of cobalt ferrite was conducted using carbonaceous microspheres prepared from a glucose solution as a sacrificial template, followed by subsequent heat treatment. The Fe/Co molar ratio in cobalt ferrite depends significantly on the initial Fe/Co molar ratio. The Fe/Co molar ratio as 1/1 could provide the stoichiometric cobalt ferrite (CoFe2O4) with a hollow sphere structure and large saturation magnetization. The simultaneous quantification of ascorbic acid (ASA), acetaminophen (ACE), and caffeine (CAF) was performed utilizing the differential pulse anodic stripping voltammetric method with CoFe2O4 modified glassy carbon electrode. The detection limits in the linear range of 0.2–4.4 µM are 0.313, 0.267, and 0.226 µM for ASA, ACE, and CAF, respectively. This proposed method enables the simultaneous detection of ASA, ACE, and CAF in pharmaceutical formulations and beverage samples. The determined concentration of the analytes is comparable with that obtained with HPLC.

Flow Restrictors and Reduction of Accidental Ingestions of Over-the-Counter Medications

Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were added to pediatric liquid single-ingredient acetaminophen formulations. The hypothesis of this study is that implementation would be associated with reduced volume and severity of pediatric acetaminophen exposures reported to the U.S. National Poison Data System. This study describes accidental unsupervised ingestions of acetaminophen in children aged <6 years. Exposures were grouped into pre-implementation (pre-period; January 4, 2010-July 17, 2011); transition (July 18, 2011-July 15, 2012); and post-implementation (post-period; July 16, 2012-December 25, 2016) periods. Cumulative and annual rates of change per million units (i.e., bottles) sold were calculated for the pre- and post-periods for acetaminophen and pediatric liquid ibuprofen (comparator without flow restrictors). Pre- to post-period rate ratios were used to compare products and to estimate the potential effect on other over-the-counter medications. Analysis was conducted in 2017 and 2018. The pre- and post-period cumulative acetaminophen exposure rate was 507.2 (95% CI=481.1, 534.6) and 325.6 (95% CI=305.8, 346.7) per 1 million units sold, respectively. Declines in the pre- versus post-period rate ratios were seen for exposures with any effect (0.642, 95% CI=0.591, 0.696) and with clinically significant outcomes (0.728, 95% CI=0.581, 0.913). In the post-period, acetaminophen exposures decreased faster than ibuprofen with a rate of change ratio of 0.936 (95% CI=0.912, 0.960) for all exposures and 0.939 (95% CI=0.909, 0.970) for exposures with any effect. The addition of flow restrictors to pediatric liquid acetaminophen was associated with a reduction in the number and severity of exposures. Application of flow restrictors to other liquid medications should be considered.

Supratherapeutic Dosing of Acetaminophen in Iranian Hospitalized Adult Patients

Background: Acetaminophen is the most commonly used analgesic and fever-lowering agent that is prescribed in a high percentage of patients. Due to the high prevalence of the administration of this drug, even a small percentage of errors in prescription can be significant and have important implications. The aim of the present study was to determine the frequency of supratherapeutic dosing of acetaminophen among hospitalized adult patients and its association with clinical outcomes. Methods and Materials: We conducted a retrospective, cross sectional study of all hospitalized adult patients in a teaching hospital affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. Results: During the three-month study period, 4,781 (24.83%) out of 19,252 hospitalized cases received acetaminophen. Of those who received acetaminophen, 264 (5.5%) cases received a supratherapeutic dose at least once. Of 611 incidences of supratherapeutic dosing, 99.1% occurred in surgical wards and surgical intensive care units (ICUs), and 98.8% was associated with receiving parenteral formulations of acetaminophen. Multivariate analysis indicated supratherapeutic dosing of acetaminophen was significantly associated with multiple factors including female gender, older age, and longer length of hospital stays. Conclusion: All things considered, the percentage of hospitalized adult patients who received any dose of acetaminophen at our center was considerably less than other countries. Despite this, the frequency of instances of supratherapeutic dosing of this medication was significant (i.e. 17.6 days per 1,000 patient-days). Considering recent reports concerning the risk of hepatotoxicity associated with the repeated use of supratherapeutic doses of acetaminophen, continuous monitoring of acetaminophen utilization in order to prevent these instances is needed. Furthermore, based on the low percentage of patients who receive acetaminophen at our center, conducting research to study the pattern of prescription of analgesics and antipyretics in our center and its association with clinical outcome is logical.