Combination Products Research Articles

Uncertain random optimal control model for deteriorating inventory with the finite horizon

This paper examines a deteriorating inventory model with combined pricing and production during a limited selling time in an uncertain random setting. Demand is influenced by market size and price, which are portrayed in terms of random variables. The uncertainty factors affecting the inventory are represented by multiple Liu processes. Inventories deteriorate by a certain percentage and back-orders for inventories are permitted. This study aims to determine the optimal level of production rate and pricing that maximizes the producer’s total expected profit through the application of uncertain random optimal control theory, which is based on uncertain theory and probability theory. Numerical examples are used to compare joint pricing dynamic production model with dynamic production model under an optimal static price, highlighting the benefits of implementing joint pricing dynamic production model. Furthermore, it is evident that an increase in deterioration rate results in decreased on-hand inventory, yet higher production rate and price. It should also be noted that different levels of probability expectation of demand can have an impact on production inventory problem.

Cutaneous pharmacokinetics-based bioequivalence: A clinical dermal open flow microperfusion verification study using lidocaine and prilocaine combination topical products

BackgroundUsing accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical generic drug products. A clinical dermal open flow microperfusion (dOFM) study has previously demonstrated the BE of topical drug products containing a hydrophilic drug. However, the utility of dOFM to evaluate the topical BE of drug products containing moderately lipophilic drugs, more representative of most topical drugs, has not yet been established. ObjectiveTo evaluate the ability of a clinical dOFM study to assess BE of topical products containing two moderately lipophilic drugs that have only minor differences in chemical and physical properties. MethodsThe study included 20 healthy subjects. Four application sites on each thigh were treated with fixed dose lidocaine/prilocaine combination products, and dermal drug concentrations were monitored with two dOFM probes per application site for 12 h. A reference cream was compared to itself and to an approved generic cream (both serving as positive controls for BE), and to a gel (negative control). BE was established based on AUC0to12h and Cmax using the scaled-average-BE approach. Systemic exposure of both drugs was assessed throughout the study. ResultsBE was successfully demonstrated for the positive controls, and not for the negative control, for both drugs. The systemic exposure of both drugs was negligible. ConclusionsdOFM accurately demonstrated BE between bioequivalent topical creams, sensitively discriminated between different formulations and differentiated the cutaneous PK of both study drugs, even though they differ only slightly in chemical and physical properties. These results support the utility of dOFM as a cutaneous PK-based BE approach for topical lipophilic drugs, including lidocaine and prilocaine.

Review study of Psoriasis in Iraq

Abstracts are written in Indonesian and English. Describe the introduction, the purpose of writting, research methods, result and conclusion. Minimum 150 and maximum 250 words.. Psoriasis is a multisystem inflammatory disease with predominantly skin and joint involvement. Beyond the physical dimensions of disease, psoriasis has an extensive emotional and psychosocial effect on patients, affecting social functioning and interpersonal relationships. As a disease of systemic inflammation, psoriasis is associated with multiple comorbidities, including cardiovascular disease and malignancy. The diagnosis is primarily clinical and a skin biopsy is seldom required. Depending on the severity of disease, appropriate treatment can be initiated. For mild to moderate disease, first-line treatment involves topical therapies including corticosteroids, vitamin D3 analogues, and combination products. These topical treatments are efficacious and can be safely initiated and prescribed by primary care physicians. Patients with more severe and refractory symptoms might require further evaluation by a dermatologist for systemic therapy .Psoriasis is a chronic, noncommunicable, painful, disfiguring and disabling disease for which there is no cure and with great negative impact on patients’ quality of life . It can occur at any age. The etiology of psoriasis remains unclear. Psoriasis can also be provoked by external and internal triggers, including mild trauma, sunburn, infections, systemic drugs and stress . Psoriasis involves the skin and nails, and is associated with a number of comorbidities. Skin lesions are localized or generalized, mostly symmetrical, sharply demarcated, red papules and plaques, and usually covered with white or silver scales. Lesions cause itching, stinging and pain. Individuals with psoriasis are reported to be at increased risk of developing other serious clinical conditions such as cardiovascular and other noncommunicable diseases . Psoriasis causes great physical, emotional and social burden . Disfiguration, disability and marked loss of productivity are common challenges for people with psoriasis. Topical and systemic therapies as well as phototherapy are available.

Combining nursery closed-system and pond grow-out common carp (Cyprinus carpio) production is a profitable business in Hungary

Extensive, large-scale long-term pond fish production has several challenges and high economic risks, such as continuous bird predation. Moreover, common carp (Cyprinus carpio) production costs are relatively high using this production strategy. To reduce risks and improve production safety and efficiency, European common carp farmers are challenged to shorten the classic 3-year production cycle. This study aimed to comprehensively analyze the main farm parameters, production efficiency, cost and revenue of a production strategy based on combining hatchery/nursery closed-system, a second phase of the nursery in ponds and a final phase of pond grow-out of common carp. A deterministic economic model was used. Combined production has a lower fish loss by bird predation, a shorter production cycle, a better feed conversion ratio than conventional pond fish production, and a similar yield at a cost of approximately 2.02 USD/kg. This value are higher than those assumed in the conventional extensive 3-year common carp, completely pond-based production strategy. However, the current assets turnover ratio is much lower in the latter case. The yearly average net revenue can increase by implementing a more intensive combined production strategy. The combined strategy can improve security and predictability of production while reducing the pond area used for grow-out of extensive common carp farm.

Nutritional and Herbal Supplements for Weight Loss Management: A Review

Abstract: Millions of dollars have been spent on nutritional and herbal supplements, which are used by many overweight people to lose weight. However, there are concerns about the effectiveness and safety of several supplements. By boosting energy expenditure, satiety, fat oxidation, inhibiting dietary fat absorption, moderating carbohydrate metabolism, raising fat excretion, increasing water elimination, and improving mood, supplements are thought to aid in weight reduction. This study provides an overview of the present status of the research on a few particular dietary supplements, herbal combinations, and combination products, as this field is evolving quickly. More studies on numerous supplements are required to verify their efficacy because they have not been examined in randomised controlled trials. Nutritionists and medical experts should go through dietary supplement use with patients and notify the FDA of any negative side effects. Additional rules would be required for the manufacture, sale, and marketing of these supplements.

ENLIGHTED phase 3 study: Efficacy and safety of padeliporfin vascular targeted photodynamic therapy (VTP) for treatment of low-grade upper tract urothelial cancer (LG UTUC).

TPS4622 Background: Padeliporfin VTP has demonstrated safety and efficacy for UTUC treatment in a Phase 1 study (NCT03617003). Padeliporfin VTP is a combination product: a drug, padeliporfin administered IV; a device: a laser light delivery system/laser-source of light emitting near-infrared (NIR) light at 753nm; and an optic fiber delivering the light endoluminally to the vicinity of UTUC tumors within the collecting system. We report the preliminary efficacy and safety outcomes of Padeliporfin VTP for Treatment of LG UTUC in ENLIGHTED, a Phase 3 trial (NCT04620239). Methods: This is an open-label phase 3 study from USA, EU and Israel. Key inclusion criteria is up to 2 biopsy-proven LG UTUC with index tumor ≤15mm in the kidney and≤20mm in the ureter with an absence of high-grade cells on cytology. VTP is performed via retrograde upper tract endoscopy under anesthetic and low light conditions, Padeliporfin is injected IV and a laser light diffuser fiber 20-40 mm is positioned in proximity of the tumor through the scope. After Padeliporfin injection, the laser fiber is illuminated for 10 min. The fiber can be repositioned to provide up to 3 treatments within the upper tract. Patients are treated in two phases: Induction(ITP) and Maintenance Treatment Phases (MTP). ITP consists of 1-3 VTPs provided at 4-week intervals until achieving complete response (CR) or treatment failure. Patients achieving CR will proceed to the MTP and be followed with endoscopic evaluation every 3 months with VTP provided for recurrent tumors only up to 12 months. Patients with high-grade recurrences will be deemed treatment failures and removed from the study to standard of care treatment. Patients completing the MTP, will be followed for an additional 48 months for long-term outcomes. Primary outcome is CR on endoscopic evaluation and selective cytology at the time of primary response evaluation (28 ± 3 days post last treatment) during padeliporfin VTP ITP. A total of 100 patients are to be enrolled. As of 21 Jan 2024, 17 patients have been treated. 13 patients completed ITP and had CR 10/13 (77%) and PR 3/13 (23%). Patients baseline characteristics: age 67±12 years; gender: 9(53%) males and 8(47%) females; tumors location: 5(29%) in ureter, 13(76%) in the kidney; number of tumors: 7(41%) 2 tumors, 10(59%) 1 tumor. The most frequent treatment related adverse events were: flank pain 17%, vomiting 8%, fatigue 8%, nausea 6%, hematuria 6%, all Grade 1-2, resolved within few days. Grade 3 serious adverse events 9% (flank pain, hypertension, renal colic, urinary tract infection) were resolved within 2-7 days. To date Padeliporfin VTP has shown evidence of safety and efficacy with preliminary data that is consistent with prior experience. Recruitment for the ENLIGHTED trial is ongoing with results expected to provide basis for approval of a new therapy that clinically benefits pts. Clinical trial information: NCT04620239 .

Understanding Disturbance Regimes From Patterns in Modeled Forest Biomass

AbstractNatural and anthropogenic disturbances are important drivers of tree mortality, shaping the structure, composition, and biomass distribution of forest ecosystems. Differences in disturbance regimes, characterized by the frequency, extent, and intensity of disturbance events, result in structurally different landscapes. In this study, we design a model‐based experiment to investigate the links between disturbance regimes and spatial biomass patterns. First, the effects of disturbance events on biomass patterns are simulated using a simple dynamic carbon cycle model based on different disturbance regime attributes, which are characterized via three parameters: μ (probability scale), α (clustering degree), and β (intensity slope). 856,800 dynamically stable biomass patterns were then simulated using combined disturbance regime, primary productivity, and background mortality. As independent variables, we use biomass synthesis statistics from simulated biomass patterns to retrieve three disturbance regime parameters. Results show confident inversion of all three “true” disturbance parameters, with Nash‐Sutcliffe efficiency of 94.8% for μ, 94.9% for α, and 97.1% for β. Biomass histogram statistics primarily dominate the prediction of μ and β, while texture features have a more substantial influence on α. Overall, these results demonstrate the association between biomass patterns and disturbance regimes. Given the increasing availability of Earth observation of biomass, our findings open a new avenue to understand better and parameterize disturbance regimes and their links with vegetation dynamics under climate change. Ultimately, at a large scale, this approach would improve our current understanding of controls and feedback at the biosphere‐atmosphere interface in the present Earth system models.

Pharmacokinetics of a Fixed-Dose Combination Product of Amlodipine, Losartan, Ezetimibe, and Rosuvastatin and Its Comparison with Co-administration of Four Individual Components in Healthy Participants.

This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Use of electronic health record data to examine administrations of pro re nata analgesics during hip fracture post-acute care.

Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.

Study on multi-stage adjust mechanism of downhole stratification control tool for natural gas hydrate multi-gas combined production gas lift

Accurate control of natural gas flow and pressure is essential to achieving multi-gas combined production of the natural gas hydrates. In this study, a downhole stratification control tool for controlling natural gas flow rate and pressure with a multi-stage throttling structure was innovatively proposed. The multi-stage throttling structure combined an adjustable cage sleeve and a fixed nozzle. The numerical model of the internal flow field of the downhole stratification control tool was established. Through the computer fluid dynamics numerical simulation, the flow field change law inside the spool module of the downhole stratification control tool under different spool structures, different outlet pressures, and different spool openings was analyzed. Moreover, the spool module prototype was processed, and the indoor experiment of the spool's performance of reducing pressure and regulating production was carried out. The results show that the multi-stage throttling structure has the advantages of adjustable spool opening and moderate cooling range and the mass flow of gas inside the spool changes linearly with the opening of the spool. The spool module can accurately control the mass flow of natural gas under high-pressure conditions, and meet the needs of the downhole stratification control tool for accurate gas control.

Design of a Fertilizing Robot Application with Regard to Energy Consumption

Electrically driven agricultural robots experience faster battery depletion than vehicles moving on asphalt because higher rolling and traction resistance require more energy. The problem arises in areas without access to the electrical grid, where charging electrically driven agricultural robots is not possible, resulting in interruptions to the robot's continuous operation. A combined energy production station powered by biogas, hydrogen, and solar energy with the prototype of autonomous fertilizing robot for blueberry plantations, to perform plant-based precision fertilization on depleted milled peat fields was created by the agrorobotics working group of the Estonian University of Life Sciences [1, 2]. The station includes unique components such as an automatic battery exchange system and an electric generator with a membrane motor. These, together with a solar energy and electric generator control system, as well as a battery charger, are mounted on a mobile platform (Figure 1). The objective of this article was to determine the energy requirements of an autonomous fertilizing robot during movement in the field and for carrying out technological operations. For this purpose, the mechanical power and energy required for the operation of the robot fertilizer spreader were first determined. Based on this, an accumulator with suitable power and capacity for the operation of the robot fertilizer spreader was selected. The travel distance of the robot on a single charge of the chosen accumulator was determined, as well as the traction power efficiency and specific power.

The role of natural anti-oxidants in gut microbiota alteration subsequent to high fat diet (HFD)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PON-MIUR 000_78 Evidence exists that the gut microbiota contributes to the alterations of lipid metabolism associated with high-fat diet (HFD). Moreover, the gut microbiota has been found to modulate the metabolism and absorption of dietary lipids, thereby affecting the formation of lipoproteins occurring at the intestinal level as well as systemically, though the pathophysiological implication of altered microbiota composition in HFD and its role in the development of atherosclerotic vascular disease (ATVD) remain to be better clarified. Recently, evidence has been collected indicating that supplementation with natural polyphenols and fibres accounts for an improvement of HFD-associated intestinal dysbiosis, thereby leading to improved lipidaemic profile. This study aimed to investigate the protective effect of a bergamot polyphenolic extract (BPE) containing 48% polyphenols enriched with albedo and pulp-derived micronized fibres (BMF) in the gut microbiota of HFD-induced dyslipidaemia. In particular, rats that received an HFD over a period of four consecutive weeks showed a significant increase in plasma cholesterol, triglycerides and plasma glucose compared to a normal-fat diet (NFD) group. This effect was accompanied by body weight increase and alteration of lipoprotein size and concentration, followed by high levels of MDA, a biomarker of lipid peroxidation. Treatment with a combination of BPE plus BMF (50/50%) resulted in a significant reduction in alterations of the metabolic parameters found in HFD-fed rats, an effect associated with increased size of lipoproteins. Furthermore, the effect of BPE plus BMF treatment on metabolic balance and lipoprotein size re-arrangement was associated with reduced gut-derived lipopolysaccharide (LPS) levels, an effect subsequent to improved gut microbiota as expressed by modulation of the Gram-negative bacteria Proteobacteria, as well as Firmicutes and Bacteroidetes. This study suggests that nutraceutical supplementation of HFD-fed rats with BPE and BMP or with their combination product leads to restored gut microbiota, an effect associated with lipoprotein size re-arrangement and better lipidaemic and metabolic profiles.

Optimized system for combined production of electricity/green hydrogen for multiple energy pathways: a case study of Egypt

Abstract By optimal sizing of a wind/photovoltaic hybrid renewable-energy (RE) system, trimming the surplus capacity to reduce the fluctuations in the electricity supplied to the grid, and using it to produce green hydrogen through electrolysis, a stable output with maximum possible capacity factor (CF) is generated to maintain the electricity grid stability. Simultaneously, the trimmed energy is used in a secondary conversion path that minimizes the weighted average cost of the energy generated from the entire plant. This surplus power-to-gas conversion allows the use of green hydrogen to produce electricity, methanol, or ammonia subject to the resource availability, site characteristics, and financial feasibility. Based on robust site selection criteria, the best performance is obtained at two sites: Ras Ghareb and Minya, achieving the lowest energy cost with some variance in their performance. For the Ras Ghareb site, the optimally sized RE plant provided the grid with a quasi-steady capacity of 423 MW with a CF of 80.04% and was capable of injecting 2965.8648 GWh throughout the year with the lowest cost of 2.4355 ¢/kWh. A surplus of 3.9% of the total energy produced from the plant was directed to produce 1922-ton H2/year, achieving the lowest cost of hydrogen production of $1.9745/kg H2. For the other selected site, Minya, the clipped energy is used to produce 3330.47-ton H2/year with an optimized lowest cost of $3.5268/kg H2. The difference in hydrogen costs was attributed to the number of full operating hours of the electrolyser in both sites. The cost is mainly affected by the electricity price and the electrolyser cost. With both tending to decrease, future forecasts show hydrogen cost reductions.

Stability Indicating RP-UPLC Method for Impurity Profiling of Darunavir and Ritonavir in Fixed Dose Drug Combination Product

Stability Indicating RP-UPLC Method for Impurity Profiling of Darunavir and Ritonavir in Fixed Dose Drug Combination Product

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug-device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). The STOP 101 was a Phase 1 open-label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open-label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9-15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4-17.1) at 5 min post-dose, persisting up to 30 min post-dose for systolic BP (6.3 mmHg; 95% CI 3.0-9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9-11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non-serious, vascular treatment-emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off-protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications.

The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.

Development and assessment of immediate-release tablets containing clopidogrel bisulphate & aspirin-strategy for optimizing the combination formulation.

The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.

Are the Nutritional Properties of Organic Tomatoes Altered by Single and Combined Microbial Soil Inoculants?: A Multiperspective Approach

Biologically active compounds are key-important ingredients of tomato fruits, especially those produced by organic agricultural practices. Being biologically effective soil treatments, microbial inoculants can improve soil quality through a variety of mechanisms. Their activity can influence soil properties and plant development, thereby determining the quantity and quality of the crop. However, little research was done on how these inoculants affect the nutritional quality of the tomato fruit and on the antioxidant status of the fruits. This study investigated lycopene content and total antioxidant capacity of organically grown tomato fruits (Solanum lycopersicum L. var. ‘Mobil’) using various types of single and combined bioeffector products in two growing seasons. Single inoculation contained Trichoderma harzianum, plant growth promoting Pseudomonas sp., and phosphorus-mobilizing Bacillus amyloliquefaciens strains. The combined treatment consisted of biotic Trichoderma harzianum, Pseudomonas fluorescens, and Bacillus subtilis strains with abiotic micronutrients of zinc and manganese. Sum of ranking differences method, as a multicriteria optimization method, was used to rank the treatments and identify the ones deviating the least from the reference treatment. The results showed that all microbial soil inoculants positively affected tomato lycopene content. The combined treatment showed significantly higher lycopene content than the Control in both years. We found that weather and climate conditions also greatly influence the total antioxidant capacity. Based on our results, we recommend the use of combined bioeffective treatments to improve the food quality value of tomato fruits.

Evaluation of a concentrated solar power-driven system designed for combined production of cooling and hydrogen

The current technique of hydrogen generation and cooling production raises climatic problems, which calls for the investigation of cleaner alternatives. No research has been conducted to propose and analyze a solar thermal power cycle-based water electrolysis for on-site production of hydrogen and the detailed exergy analysis of a series flow double-effect absorption chilling machine employed for large solar cooling. In this regard, a helically coiled tube embedded central receiver is used in the heliostat field for the simultaneous production of solar cooling and green hydrogen to meet the increasing needs of energy and fuel sustainably. The combined system is composed of four sub-systems including a heliostat field, LiBr–H2O operated series-flow double effect absorption refrigeration cycle (DEARC), organic Rankine cycle (ORC), and proton exchange membrane (PEM) electrolyzer. The system was examined from energy and exergy perspectives in the Engineering Equation Solver (EES) using library data of REFPROP for obtaining the thermodynamic properties of working fluids. The results of the thermodynamic model for the combined system are validated. Furthermore, the effect of ambient temperature, solar irradiation, and type of ORC working fluid on the hydrogen and cooling production, and the overall energy and exergy efficiency of the combined system are examined. A computational fluid dynamics simulation applying ANSYS-FLUENT was used to examine how coil curvature ratio and coil torsion affect solar heat transfer fluid (SHTF) pressure and temperature leaving the receiver. The coil curvature ratio affects temperature increase more than coil torsion. Solar heat transfer fluid outlet temperature increases by 36.9 % when the coil curvature ratio increases from 0.063 to 0.095 at direct normal irradiations (DNI) 1200 W/m2, input temperature of 92°C, and coil torsion of 0.032. The response of the cogeneration cycle to varying operating parameters is examined. Application of R141b as the ORC fluid results in a large increase of cooling exergy efficiency from 14.98 % to 63.48 % when the ambient temperature is increased from 15 °C to 45 °C whereas the exergy efficiency of the combined system is marginally improved. The exergy distribution presents for ORC operating on R141b, out of 100 % input solar exergy, 16.42 % is generated as hydrogen exergy and 13.67 % cooling exergy, 66.79 % is the exergy destroyed, and the rest 3.12 % is exergy loss. Exergy analysis is utilized to identify the sources of losses in useful energy within the components of the system considered and provides a more realistic and meaningful assessment than the traditional energy analysis. The results justify a need for the promotion of exergy analysis through policy decisions in the context of the global energy and environment crisis.

Call combination production is linked to the social environment in Western Australian magpies (Gymnorhina tibicen dorsalis).

It has recently become clear that some language-specific traits previously thought to be unique to humans (such as the capacity to combine sounds) are widespread in the animal kingdom. Despite the increase in studies documenting the presence of call combinations in non-human animals, factors promoting this vocal trait are unclear. One leading hypothesis proposes that communicative complexity co-evolved with social complexity owing to the need to transmit a diversity of information to a wider range of social partners. The Western Australian magpie (Gymnorhina tibicen dorsalis) provides a unique model to investigate this proposed link because it is a group-living, vocal learning species that is capable of multi-level combinatoriality (independently produced calls contain vocal segments and comprise combinations). Here, we compare variations in the production of call combinations across magpie groups ranging in size from 2 to 11 birds. We found that callers in larger groups give call combinations: (i) in greater diversity and (ii) more frequently than callers in smaller groups. Significantly, these observations support the hypothesis that combinatorial complexity may be related to social complexity in an open-ended vocal learner, providing an important step in understanding the role that sociality may have played in the development of vocal combinatorial complexity. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics'.