US Pharmacopeia Research Articles

Development and Validation of Methodologies for the Identification of Specialized Pro-Resolving Lipid Mediators and Classic Eicosanoids in Biological Matrices.

Lipid mediators, which include specialized pro-resolving mediators and classic eicosanoids, are pivotal in both initiating and resolving inflammation. The regulation of these molecules determines whether inflammation resolves naturally or persists. However, our understanding of how these mediators are regulated over time in various inflammatory contexts is limited. This gap hinders our grasp of the mechanisms underlying the disease onset and progression. Due to their localized action and low endogenous levels in many tissues, developing robust and highly sensitive methodologies is imperative for assessing their endogenous regulation in diverse inflammatory settings. These methodologies will help us gain insight into their physiological roles. Here, we establish methodologies for extracting, identifying, and quantifying these mediators. Using our methods, we identified a total of 37 lipid mediators. Additionally, by employing a reverse-phase HPLC method, we successfully separated both double-bond and chiral isomers of select lipid mediators, including Lipoxin (LX) A4, 15-epi-LXA4, Protectin (PD) D1, PDX, and 17R-PD1. Validation of the method was performed in both solvent and surrogate matrix for linearity of the standard curves, lower limits of quantitation (LLOQ), accuracy, and precision. Results from these studies demonstrated that linearity was good with r2 values > 0.98, and LLOQ for the mediators ranged from 0.01 to 0.9 pg in phase and from 0.1 to 8.5 pg in surrogate matrix. The relative standard deviation (RSD) for inter- and intraday precision in solvent ranged from 5% to 12% at low, intermediate, and high concentrations, whereas the RSD for the inter- and intraday variability in the accuracy ranged from 95% to 87% at low to high concentrations. The recovery in biological matrices (plasma and serum) for the internal standards used ranged from 60% to 118%. We observed a marked ion suppression for molecules evaluated in negative ionization mode, while there was an ion enhancement effect by the matrix for molecules evaluated in positive ionization mode. Comparison of the integration algorithms, namely, AutoPeak and MQ4, and approaches for calculating signal-to-noise ratios (i.e., US Pharmacopeia, relative noise, peak to peak, and standard deviation) demonstrated that different integration algorithms tested had little influence on signal-to-noise ratio calculations. In contrast, the method used to calculate the signal-to-noise ratio had a more significant effect on the results, with the relative noise approach proving to be the most robust. The methods described herein provide a platform to study the SPM and classic eicosanoids in biological tissues that will help further our understanding of disease mechanisms.

Metabolomic approach reveals the mechanism of synthetic communities to promote high quality and high yield of medicinal plants—danshen (Salvia miltiorrhiza Bge.)

BackgroundSalvia miltiorrhiza Bunge, a significant and widely used medicinal herb, is also recognized in the US Pharmacopoeia as a dietary supplement. However, the decline in yield and quality limits its further development as a traditional herbal medicine. Therefore, a deeper understanding of how synthetic communities (SynCom) affect the quality and yield of S. miltiorrhiza and the underlying mechanisms is necessary.ResultsIn this study, we selected S. miltiorrhiza as the research subject and designed two synthetic communities (SynCom 1 and SynCom 2) using five endophytic fungi without significantly growth-promoting effect. We conducted both greenhouse and field experiments to investigate their impact on the yield and quality of the herbal plants. Greenhouse experiments confirmed that SynCom 1 significantly increased the biomass of S. miltiorrhiza, whereas SynCom 2 had the opposite effect. Field experiments further demonstrated that the application of SynCom 1 promoted photosynthesis and enhanced carbon and nitrogen metabolism, steady and markedly promoted plant growth, and thus increased S. miltiorrhiza yield compared to the uninoculated. In contrast, SynCom 2 inhibited yield but increased the content of the main active components. Un-targeted metabolomics analysis showed that SynCom 1 mainly promoted tricarboxylic acid cycle and nitrogen assimilation process to increase yield, and SynCom 2 mainly increase substrate content in the salvianolic acid and tanshinone synthesis pathways to improve quality.ConclusionThese beneficial qualities exhibited by SynComs composed of fungi without apparent growth-promoting abilities represent an untapped resource that can be leveraged to enhance crop productivity. This opens up new research avenues for precision manipulation of plant microbiomes.Graphical abstract

Advice to the US FDA to Allow US Pharmacopeia to Create Biological Product Specifications (BPS) to Remove Side-by-Side Analytical Comparisons of Biosimilars with Reference Products.

Pharmacopeia monographs are not intended to establish biosimilarity. However, the US Food and Drug Administration (FDA) has stopped the US Pharmacopeia (USP) from creating monographs for biological drugs due to the need for side-by-side comparisons with the reference products. The USP can create Biological Product Specifications (BPS), not to be labeled as monographs, based on the analytical testing of reference products and validated test methods that will remove the need for side-by-side analytical testing of biosimilars with reference products. Scientific arguments confirm that this plan is logical and capable of creating global quality standards for biosimilars to allow their interchangeability with other biosimilars. While the regulatory agencies have waived many high-cost biosimilar tests, analytical assessment is the most sensitive test; reducing its cost will further enhance the entry of biosimilars with no clinically meaningful difference.

Development of SIMPATEC-USP: An abbreviated impactor for rapid testing of inhalation devices

Cascade impactors like the Andersen Cascade Impactor (ACI) and Next Generation Impactor (NGI) are complex and costly due to multiple stages. This study introduces SIMPATEC-USP (Simplified Impactor Developed at the University of São Paulo), a low-cost, single-stage alternative meeting US Pharmacopeia standards for testing dry powder inhalers (DPIs). SIMPATEC-USP simplifies particle retention into a single Petri dish stage, eliminating multi-stage complexity. Its design includes a straightforward closure system for easy assembly/disassembly. A collection chamber holds a glass Petri dish with filter paper for final filtration, ensuring efficient aerosol product collection. SIMPATEC-USP also offers potential use with culture media for applications like antibacterial screening. Operating at 30 L/min, SIMPATEC-USP consists of three parts: a single-stage chamber, an L-shaped tube mimicking the trachea, and a vacuum pump. Aerosol particles are deposited onto the Petri dish via a nozzle, and the collected sample is weighed to determine drug concentration. Tested with inhalation-grade lactose, SIMPATEC-USP effectively collects and analyzes particles, allowing for rapid aerodynamic comparison of formulations, capsule retention assessment, and sample collection for drug release studies. The results demonstrate that it is possible to evaluate the performance of three inhalation devices regarding the mass migrating to the collection plate and that retained within the device itself. In conclusion, SIMPATEC-USP is highly suitable for exploratory studies and educational activities in pharmaceutical technology and pulmonary drug delivery systems.

An Insight Into Risk Assessment and Reformulation of Drug Products Manufactured Using Benzene Grade Carbomer: A Regulatory Perspective.

Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance.There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies.This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.The decision of the USFDA to restrict the usage of high benzene content of carbomer in the formulation is a welcome move. This article has shown a way for researchers to see opportunities in the path and provide best-in-class medicines to patients with a better formulation safety profile.

Evaluation of Dissolution Release Profiles of Nicotine and Three Distinct Flavor Markers in Loose Moist Smokeless Tobacco Products

Summary This study describes the dissolution release profiles of nicotine and flavor markers from three loose moist smoke-less tobacco (MST) products, same brand, each made with a distinct flavor. The US Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4) was employed, following a previously published method that was validated to study the nicotine release from MST products. Herein, we expanded the scope of the analytical method by incorporating three flavor markers including methyl salicylate, ethyl salicylate, and glycyrrhizic acid to provide an understanding of the dissolution release profiles of not only nicotine but also of flavor markers. The dissolution release profiles of nicotine were found to be equivalent across all three tobacco products. In contrast, the release profiles of the studied flavor markers exhibited distinct differences, primarily influenced by their chemical properties, particularly polarity. Notably, glycyrrhizic acid demonstrated the most rapid release rate, while ethyl salicylate exhibited the slowest release rate. This study serves as a valuable resource for researchers, manufacturers, and regulatory bodies involved in the evaluation of MST products attributes and performance.

Medicated Chewing Gums: A Revolution in Self-Medication And Drug Delivery

Medicated chewing gums (MCGs) are characterized as ‘solid single-dose preparations with a base consistingmainly of gum that is intended to be chewed but not to be swallowed, providing a slow steady release of themedicine contained’. The European Pharmacopoeias (Ph. Eur) along with the U.S. Pharmacopoeias (USP)formally acknowledged medicated chewing gums as an acceptable method for medication administration.MCGs have become a new and exciting method in the realm of oral drug delivery. The potential benefits ofchewing gums over conventional drug delivery method are examined in this review paper. Notable benefitsinclude the circumvention of hepatic first-pass effect, patient compliance, local and systemic action, andvarious other advantages that make them an exciting alternative in pharmaceutical research. Thiscomprehensive review paper covers all essential aspects related to medicated chewing gums, including theircomposition, advantages, disadvantages, methods of preparation, and future trends. It also underscores thepotential of medicated chewing gums as a useful substitute to buccal medication delivery and emphasizestheneed for further exploration and research in this field.

An Improved HPLC Separation Method for TSPO Radioligand [11C]ER176 Clinical Production.

Mitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi-preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5-9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.

Modified Release of Acetaminophen from Matrix Tablet Formulations: Influence of Tablet Geometry

Background: Acetaminophen (APAP) or paracetamol is a widely used over-the-counter, analgesic (common conditions treated include headaches, backache, toothache, muscle aches, arthritis, sore throat etc.) and antipyretic drug. It can be administered orally, in the form of a tablet (plain, effervescent, orodispersable, etc.) or liquid, rectally in the form of a suppository or by injection (intravenously or intramuscularly). It is well absorbed orally with a plasma elimination half-life ranging from 1 to 4 h. The modified release oral formulation can prolong its therapeutic effects by maintaining APAP average plasma concentrations. Objective: In the context of this work, two APAP formulation tablets with different geometries were produced from standard pharmaceutical excipients to investigate the role of altered tablet geometry in modified oral drug delivery. Methods: APAP tablets were prepared by direct compression, using hydroxypropyl methylcellulose (HPMC K15M), polyvinylpyrrolidone (PVP, MW: 55,000) and magnesium stearate, as ingredients. The release profiles were probed in aqueous dissolution media (pH 1.2 and 6.8) to simulate the conditions in the gastrointestinal tract in a United States Pharmacopeia (USP) dissolution paddle apparatus II and analyzed using an ultraviolet (UV) spectrophotometer (λmax = 244 nm). Results: The results indicated that the tablets were within the acceptable range of all evaluation parameters (tablet dimensions, drug content, weight variation, and breaking force) as defined by the international standards stated in the US Pharmacopoeia. The dissolution results showed that the APAP’s release profile was controlled by the tablets’ different geometries and, specifically the surface area (SA) and the surface area/volume (SA/V) ratio of the different tablets. The tablets with smaller SA/V ratios and SA showed slower drug release, indicative of a modified release motif. Conclusion: Altered tablet geometry plays an important role in APAP-modified oral drug delivery.

Comparison of In vitro Dissolution Tests of five brands of Diclofenac Sodium delayed release tablets in Moroccan market

This study aims to evaluate the similarity of in-vitro dissolution profiles, of commercially available generics of diclofenac sodium delayed-release tablets, of 25mg strength, with the innovator brand in Moroccan Market. Dissolution profiles for five brands were determined using the paddle method from the United States Pharmacopoeia. For the aptitude verification of the method, in our experimental conditions, linearity and accuracy tests were performed. The rate of dissolution was determined by Ultra-Violet Spectroscopy at 276nm. The assessment between the generics and the brand medicine was carried out under the similarity factor approach. We also presented an overview of the dissolution principles of tablet dosage form, and the pharmacopoeia dissolution test recommendations in our case. To compliance with US pharmacopoeia specifications, the rate of dissolution should be not more than 10% after 2hours in the acid stage, and not less than 75% at 45 minutes in the buffer stage. Furthermore, two dissolution profiles are considered similar when the f2 value is ≥50. According to routine quality control, evaluating the rate dissolution at the final point, all the generic medicines marketed in Morocco, meet the specification of the dissolution testing. However, using the comparison of dissolution profiles, only generic-2 is interchangeable with the innovator brand.

Characterization of residual debris on packaged hip arthroplasty stems demonstrates the dominance of less than 10 μm sized particulate: Updated USP788 guidelines for orthopedic implants.

Past evaluation of particle contamination on packaged implants has typically been conducted using US Pharmacopeia (USP) 788, a 1970s pharmaceutical guideline created to evaluate contaminant particles in injectable fluids and syringes. Our objective was to reestablish relevant acceptance criteria for residual orthopedic and other implant debris, including smaller particles (i.e., <10 μm in diameter). Packaged total hip arthroplasty (THA) titanium (Ti6Al4V)-alloy femoral stems were used (hydroxyapatite [HA]-coated and non-coated stems). Short-term ultrasonication and longer-term 24-hour soak/agitation methods were used to elute surface-bound contaminant particles, and released particles were analyzed via scanning electron microscopy, energy-dispersive x-ray analysis, image analysis, and particle characterization. For HA-coated THA-stems, >99% of eluted particles were calcium phosphate. For plain non-coated THA-stems, >99% of eluted particles were titanium-alloy-based. The number-based median size of particles in both groups was approximately 1.5 μm in diameter despite being composed of different materials. The total volume of particulate removed from HA-coated stems was 0.037 mm3 (671 × 103 particles total), which was approximately >50-fold more volume than that on plain non-coated stems at 0.0006 mm3 (89 × 103 particles total). Only non-coated THA stems passed reestablished USP788 acceptance criteria, compared by using equivalent total volumes of contaminant particulate within new and legacy guideline ranges of >10 and >25 μm ECD, that is, <1.0 × 107 particles for <1 μm diameter in size, <600,000 for <1-10 μm, <6000 for 10-25 μm and <600 for >25 μm. These results fill a knowledge gap on how much residual debris can be expected to exist on packaged implants and can be used as a basis for updating acceptance criteria (i.e., termed USP788-Implant [USP788-I]). Residual implant particulate assessment is critical given the increasing implant complexity and new manufacturing techniques (e.g., additive manufacturing).

Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages.

This study aims to establish a Flow-through Visualization Dissolution System (FVDS) that combines time-lapse macro-imaging and a flow-through cell to simultaneously elucidate dissolution and disintegration profiles. Three cefaclor extended-release tablets (CEC-1, CEC-2, CEC-3) from different manufacturers were subjected to dissolution tests using both the US Pharmacopeia basket method and the FVDS method. Two dissolution media plans were implemented in FVDS: i) Plan I involved dissolution in pH1.0 medium for 12h; ii) Plan II initiated dissolution in pH1.0 medium for 1h, followed by pH6.8 phosphate buffer for 11h. The resulting dissolution data were fitted using classic mathematical models. Pixel information was further extracted from images obtained using FVDS and plotted over time. The basket method showed the cumulative dissolution of all three tablets in pH1.0, pH4.0 and water reached 80% within 6h, but remained below 60% in the pH6.8 medium. The f2 values indicated CEC-2 was similar to CEC-1 in the pH4.0 medium, pH6.8 medium and water. Using FVDS with medium plan II, the cumulative dissolution of CEC-1 and CEC-2 reached about 80% showing similarity, while no similarity was observed between CEC-3 and CEC-1. The f2 factor of the percentage area change profiles also showed consistent results in the dissolution profile of medium plan II. However, FVDS with medium plan I cannot distinguish between CEC-2 and CEC-3. FVDS offers an alternative to traditional dissolution methods by integrating imaging analysis as a complementary tool to disintegration and dissolution testing methods.

High-Throughput Validated Optical Sensor for the Dissolution Studies of Captopril Based on Instrumental-Free Detection through an Overhead Book Scanner

A new high-throughput optical sensor for captopril (CAP) is proposed. The sensor is based on the inhibitory effect of the analyte on the specific reaction of desferal with Fe(III) in an acidic medium. The whole analytical scheme was developed in micro-plates format combined with instrumental-free detection through an overhead book scanner. Dissolution testing was selected as an interesting application due to the generation of large amounts of samples during drug development. The method allowed the quantification of CAP up to 500 μM, with a lower limit of quantification LLOQ of 25 μM. 96 samples/standards could be processed simultaneously, obtaining a complete dissolution profile within 1 h (n = 12). Following validation, the obtained results were in accordance with the HPLC method recommended by the US Pharmacopeia. Finally, the greenness of the procedure was assessed by well-established tools such as the Green Analytical Procedure and Blue Applicability Grade indexes (77.5% score).

A U.S. Pharmacopeia (USP) overview of Pan American botanicals used in dietary supplements and herbal medicines.

The United States Pharmacopeial Convention (USP) is a nonprofit, scientific, standard-setting organization, and world leader in establishing quality, purity, and testing standards for medicines, foods, and dietary supplements. USP quality standards are used in more than 140 countries and are legally recognized by more than 40 countries. Currently, there is renewed interest in herbal medicines globally, and health policies are being implemented worldwide for the use of complementary and traditional medicine. In response, USP has developed a robust body of monographs that can be used to guide industry and regulators in ensuring the quality and safety of botanical ingredients used in dietary supplements and herbal medicines. Throughout the Pan American regions, there is a strong tradition of using botanicals as herbal medicines and, as in other regions, a growing desire for botanical dietary supplements. This underscores the need for public quality standards to ensure quality, reduce the flow of substandard and adulterated products, and ensure public health and safety. In April 2022, USP launched the Pan America Botanical Dietary Supplements and Herbal Medicines Expert Panel, with experts representing 12 different countries. The Expert Panel's work focuses on developing quality control standards for the most important botanical ingredients used in the respective countries, ingredients that are also of global importance. This article provides an overview of the state of botanical dietary supplements and herbal medicines in different Pan American regions with a focus on the regulatory status of herbal products, the development of national quality and research initiatives, and policies related to agriculture conservation and sustainability, among other topics.

Evaluating drug stability and sterility in single-dose vials when accessed with a closed system transfer device.

Impact of drug wastage is a legitimate and persistent concern. Financial impact of drug waste is borne by the hospital network, patients, and healthcare systems. Measures to reduce drug wastage may have a positive impact throughout healthcare systems. This study investigated the stability and sterility of single-dose vials when repeatedly accessed with a closed system transfer device. By evaluating the sterility and stability, these results may be used to validate the extension of vial usage and lead to potential drug wastage reduction. Sterility testing was performed in accordance with US Pharmacopeia 71. A closed system transfer device was incorporated into simulated compounding tasks, utilizing growth media. Simulated compounding tasks were performed in the clinical environment, followed by incubation to stimulate growth. Stability testing was performed in accordance with US Pharmacopeia monographs at multiple timepoints post access. Test samples were comparatively tested via high-performance liquid chromatography to freshly opened vials at each timepoint. No growth was observed in test samples. Control vials displayed growth, where appropriate. The drugs retained stability, when compared to freshly opened vials at 0, 24, 48, and 72 h, post access. This study confirms that closed system transfer devices do not contribute to microbial contamination of drug vials, following the repeated access, for up to 7 days and the tested drugs retained equivalent chemical stability for up to 72 h post access. This study may offer a manner by which a facility may assess single-dose vials' sterility and stability, following repeated access by a closed system transfer device.

Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms invivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug-drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended-release formulations, where systemic exposure of nifedipine was increased in subjects after multiple-dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well-understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically-based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in invitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two-stage invitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4-mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH-dependent formulation. The reported model-based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.

Guidelines in Practice: Medication Safety.

Medication errors are preventable events that health care professionals, consumers, and medication manufacturers report to the US Food and Drug Administration. The agency receives more than 100,000 medication-related reports each year, and some reports involve patient death. A variety of sources provide perioperative nurses with information on interventions and practices to prevent medication errors, including the US Pharmacopeia, The Joint Commission, medication manufacturers' instructions for use, safety data sheets, and the updated AORN "Guideline for medication safety." This article provides an overview of the guideline and discusses recommendations for organizational oversight, procurement and storage, retrieval and preparation, labeling, and hazardous medications. It also includes a scenario that illustrates perioperative nursing practices for administering an antineoplastic medication intraoperatively. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative or procedural settings.

The Synergistic Benefit Mechanism of Medical and Recreational Marijuana: Economic Gains of Cannabis Taxation based on US Federal Law for Corporate Governance and Sustainability

Purpose: Marijuana legalization is brought about by the demands of people as social utility either for medical or recreation consumption. It is essential that the control of cannabis fulfills the goals of corporate governance and sustainability. This paper aims to measure the profitability of marijuana taxation over a time period as trend analysis of economic gains.&#x0D; Methodology: The socio-legal taxation of marijuana in the United States follows a descriptive research design. The beneficial gains of marijuana as medical use created this substance to be controlled under contract law transactions. The removal of cannabis in US Pharmacopeia modified the tort law restriction for legalization of marijuana as recreational consumption. The recreational cannabis taxation together with medical marijuana state taxes are essential to fulfill the 4 pillars of corporate governance and sustainability for strengthening constitutional rights. The legalization of marijuana through votes of the people repeals the criminal punishments imposed by federal law to advocate the synergistic concepts of economic theory.&#x0D; Findings: State tax theory creates voluntary principles in transactions together with trend analysis in prices and demands of people resulting to efficiency in mutual gains through lessening the value of participation under a harmful environment. Hence, Pigouvian tax follows the public welfare of medical marijuana and common revenue of recreational cannabis diminishes the overall costs of social consumption. Federal laws control marijuana usage through Pigouvian taxes of medical use with lessened participation in externalities and common revenue in cannabis consumption, as a legalization process of other states in reinstating tort law for business purposes, while still enforcing criminal penalties to remaining states, in compliance with US federal laws, not in favor of medical and recreational marijuana use. The economic theory supports the legalization of medical and recreational cannabis use through taxation as profitable gains by allowing voluntary market transactions of marijuana as fulfillment to corporate governance and sustainability for more allocation of public funds. From 2002 to 2018, medical and recreational cannabis users increased to 70% of social utility through lessening the value of participation, a win-win in efficiency of economic design. In 2010, marijuana taxation generated $8.7 billion as federal public funds, with accompanied criminal penalties to other states.&#x0D; Recommendations: Economic theory is a conceptual design supporting the beneficial gains of legalizing marijuana via taxation. This economic design promotes fair responsibility of market gains while still in strict compliance of enforcing criminal punishments to violators. The people’s votes for legalization of marijuana taxation indicates that this economic policy has come by choice in a particular state as constitutional right of either a medical opinion or business ethics. However, cannabis is deemed to be a substance subject for criminal liabilities, similar to other patent drugs under taxation as well. Hence, it is suggested to create artificial intelligence using authorless works for clinical trials and other relevant studies subject to patent law of marijuana use, as advocacy of public welfare and safety since voluntary transactions are apparent harmful environment.

Effect of Agar Weight Loss with Passive Continuous Air Monitoring According GMP Annex 1 2023

The GMP Annex 1 2023 requests that microbial environmental monitoring by active and passive microbial air samplers is actuated by continuous air monitoring. A prolonged sampling produces a loss of moisture in the agar of the Petri dish and therefore it is necessary that during the “continuous time” the dryness of the nutrient media is under control to guarantee a regular growing of the cfu. The purpose of this paper is to evaluate if the agar of settle plate (which volume was reduced with a treatment under sterile laminar flow before aspiration) has still the correct nutrient characteristics during the incubation. The results of the study are summarised in Table 1 and 2. The average loss of humidity after 4 hours in the first part of test under laminar flow was 14,7%. In the second part of test, the Petri dishes aspirated the air in a normal open environment and the average growth after incubation (indicated in cfu/ plate), in comparation with control plates with the original volume of agar, was 87%. The acceptance criteria using the US Pharmacopeia Validation Recommendation for microbiological examination (chapter ) is that the test plates had to recover &lt; 70% of the challenge.

Comprehension of US Pharmacopeia and South African pictograms by sub-Saharan migrants who newly arrived in Europe

BackgroundPatient understanding of health information is crucial for successful pharmaceutical care. Pharmaceutical pictograms enable communication of medication instructions to patients who may not share a common language or are illiterate. However, cultural factors can impact the accurate interpretation of these visual aids. ObjectivesThis study aimed to assess and compare the comprehensibility of two sets of pictograms from different cultural backgrounds among sub-Saharan migrants recently arrived in Europe. MethodsIn June 2022, a cross-sectional survey was conducted at the Migrant Temporary Stay Center in Melilla, Spain. Participants were randomly assigned to interpret 10 pictograms from either the U.S. Pharmacopeia or South African counterparts, with a minimum of 50 participants per group. Following the International Organization for Standardization's testing comprehensibility criterion, pictograms achieving a 66.7% correct interpretation rate were considered acceptable. Health literacy was measured using a culturally validated sub-Saharan version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Data analysis included Fisher's exact test or chi-square test (for qualitative variables) and the Mann-Whitney test (for quantitative variables). ResultsA total of 106 participants were included (51 in the U.S. pharmacopeia group and 55 in the South African group). None of the assessed pictograms met the comprehensibility criterion, and both groups exhibited high nonresponse rates. The South African pictograms were better understood than the American ones for all intended messages, with a statistically significant difference in overall comprehension (p = 0.002). Additionally, the participants' country of birth was a statistically significant factor for comprehension (p = 0.019). ConclusionsOur findings indicate that evaluated pharmaceutical pictograms cannot be validly used in newly arrived sub-Saharan immigrants in Europe. However, the significantly better comprehension of South African pictograms compared to North American ones highlights the importance of cultural alignment between pictograms and their prospective users for effective comprehensibility.