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Pharmaceutics Jun 2024The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative...
The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative composition requires the confirmation of the internal structure equivalence. The impact of the shelf-life on the parameters proposed for internal structure comparison has not been studied. The objectives of this work were: (1) to quantify the effect of the time since manufacturing on the mean value and variability of the parameters proposed by the EMA to characterize the internal structure and performance of topical formulations of a complex topical formulation, and (2) to evaluate the impact of these changes on the assessment of the microstructure equivalence. A total of 5 batches of a topical emulgel containing 1% diclofenac diethylamine were evaluated 5, 14, and 23 months after manufacture. The zero-shear viscosity (η), viscosity at 100 s (η), yield stress (σ), elastic (G') and viscous (G″) moduli, internal phase droplet size and in vitro release of the active ingredient were characterized. While no change in variability over time was detected, the mean value of all the parameters changed, especially the droplet size and in vitro release. Thus, combining data from batches of different manufacturing dates may compromise the determination of bioequivalence. The results confirm that to assess the microstructural similarity of complex formulations (such as emulgel), the 90% confidence interval limit for the mean difference in rheological and in vitro release parameters should be 20% and 25%, respectively.
PubMed: 38931871
DOI: 10.3390/pharmaceutics16060749 -
Plants (Basel, Switzerland) Jun 2024The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into...
The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is (L.) Sch. Bip., also known as (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5--p-coumaroylquinic acid, 1--p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5--dicaffeoylquinic acid, quercetin-3--malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from herb (ETIH) against pathogens such as , , and . Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract.
PubMed: 38931061
DOI: 10.3390/plants13121629 -
Molecules (Basel, Switzerland) Jun 2024An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical...
An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical formulation and rabbit skin samples. The separation was achieved using a Thermo Scientific ACCLAIM 120 C column (Waltham, MA, USA, 4.6 mm × 150 mm, 5 µm). The optimized elution phase consisted of deionized water adjusted to pH = 3 using phosphoric acid mixed with acetonitrile in a 35:65% (/) ratio with isocratic elution. The flow rate was set at 0.7 mL/min, and the detection was performed at 205 nm and 25 °C. The method exhibits good linearity for capsaicin (0.05-70.0 µg/mL), methyl salicylate (0.05-100.0 µg/mL), and diclofenac diethylamine (0.05-100.0 µg/mL), with low LOD values (0.0249, 0.0271, and 0.0038 for capsaicin, methyl salicylate, and diclofenac diethylamine, respectively). The RSD% values were below 3.0%, indicating good precision. The overall greenness score of the method was 0.61, reflecting its environmentally friendly nature. The developed RP-HPLC method was successfully applied to analyze Omni Hot Gel pharmaceutical formulation and rabbit skin permeation samples.
Topics: Capsaicin; Diclofenac; Chromatography, High Pressure Liquid; Salicylates; Skin; Animals; Rabbits; Chromatography, Reverse-Phase; Diethylamines
PubMed: 38930798
DOI: 10.3390/molecules29122732 -
Antioxidants (Basel, Switzerland) May 2024The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and...
Preliminary Investigation of subsp. : LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2.
The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the subsp. extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC value for the extract was determined to be 19.44 ± 0.04 μg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the extract, with an LC value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin's potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds.
PubMed: 38929093
DOI: 10.3390/antiox13060654 -
The Journal of Biological Chemistry Jun 2024Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of...
Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of them associated with familial amyloid cardiomyopathy (FAC). Recently, our group described a new variant of TTR in Brazil, namely A39D-TTR, which causes a severe cardiac condition. Position 39 is in the AB loop, a region of the protein that is located within the thyroxine-binding channels and is involved in tetramer formation. In the present study we solved the structure and characterize the thermodynamic stability of this new variant of TTR using urea and high hydrostatic pressure (HHP). Interestingly, during the process of purification, A39D-TTR turned out to be a dimer and not a tetramer, a variation that might be explained by the close contact of the four aspartic acids at position 39, where they face each other inside the thyroxine channel. In the presence of sub-denaturing concentrations of urea, bis-ANS binding and dynamic light scattering revealed A39D-TTR in the form of a molten-globule dimer. Co-expression of A39D and WT isoforms in the same bacterial cell did not produce heterodimers or heterotetramers, suggesting that somehow a negative charge at the AB loop precludes tetramer formation. A39D-TTR proved to be highly amyloidogenic, even at mildly acidic pH values where WT-TTR does not aggregate. Interestingly, despite being a dimer, aggregation of A39D-TTR was inhibited by diclofenac, which binds to the thyroxine channel in the tetramer, suggesting the existence of other pockets in A39D-TTR able to accommodate this molecule.
PubMed: 38925327
DOI: 10.1016/j.jbc.2024.107495 -
Pharmacy (Basel, Switzerland) Jun 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only...
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only medicines, in many countries they are frequently purchased for self-medication purposes. This study explores NSAID-usage patterns in Kosovo, aiming for a safer and more effective medicinal use. The study employed a dual approach to collect data. First, NSAID sales were analyzed in a convenience sample of ten community pharmacies across diverse regions in Kosovo in 2023. Second, data on NSAID-usage patterns and patient awareness were systematically gathered from 410 patients during routine pharmacist-patient interactions. The four most commonly purchased NSAIDs according to sales analysis were diclofenac (33.1%), ketoprofen (27.6%), ibuprofen (17.0%) and nimesulide (12.7%). A significant 74.8% of NSAIDs were bought without prescriptions, particularly among younger adults (20-39 years), who accounted for 82.8% of such purchases. The predominant reason for NSAID use was headache (43.8%). Although many of the patients suffered from occasional (33.7%) or frequent (12.6%) stomachaches and took acid-lowering medicines, the majority (85.9%) could not recall any NSAID adverse reactions. This study exposes widespread self-medication and a significant lack of awareness regarding potential risks of NSAIDs, particularly among young adults. To address these issues, it is critical to improve dispensing practices through increased pharmacist awareness and stricter law enforcement.
PubMed: 38921969
DOI: 10.3390/pharmacy12030093 -
JAMA Network Open Jun 2024Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM...
IMPORTANCE
Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
OBJECTIVE
To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023.
EXPOSURE
PIM prescription according to PIM criteria operationalized for use with FIRE data.
MAIN OUTCOMES AND MEASURES
The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries.
RESULTS
This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing.
Topics: Humans; Switzerland; Aged; Cross-Sectional Studies; Primary Health Care; Potentially Inappropriate Medication List; Female; Male; Inappropriate Prescribing; Aged, 80 and over; Prevalence; Practice Patterns, Physicians'
PubMed: 38904960
DOI: 10.1001/jamanetworkopen.2024.17988 -
Materials (Basel, Switzerland) May 2024Biochar enriched with metals has an increased potential for sorption of organic and inorganic pollutants. The aim of the research was to identify the possibility of...
Biochar enriched with metals has an increased potential for sorption of organic and inorganic pollutants. The aim of the research was to identify the possibility of using biochar composites produced on the basis of waste plant biomass and waste FFH (ferryferrohydrosol) containing iron atoms, after CO capture. The composites were produced in a one-stage or two-stage pyrolysis process. Their selected properties were determined as follows: pH, ash content, C, H, N, O, specific surface area, microstructure and the presence of surface functional groups. The produced biochar and composites had different properties resulting from the production method and the additive used. The results of experiments on the removal of methylene blue (MB) from solutions allowed us to rank the adsorbents used according to the maximum dye removal value achieved as follows: BC1 (94.99%), B (84.61%), BC2 (84.09%), BC3 (83.23%) and BC4 (83.23%). In terms of maximum amoxicillin removal efficiency, the ranking is as follows: BC1 (55.49%), BC3 (23.51%), BC2 (18.13%), B (13.50%) and BC4 (5.98%). The maximum efficiency of diclofenac removal was demonstrated by adsorbents BC1 (98.71), BC3 (87.08%), BC4 (74.20%), B (36.70%) and BC2 (30.40%). The most effective removal of metals Zn, Pb and Cd from the solution was demonstrated by BC1 and BC3 composites. The final concentration of the tested metals after sorption using these composites was less than 1% of the initial concentration. The highest increase in biomass on prepared substrates was recorded for the BC5 composite. It was higher by 90% and 54% (for doses of 30 g and 15 g, respectively) in relation to the biomass growth in the soil without additives. The BC1 composite can be used in pollutant sorption processes. However, BC5 has great potential as a soil additive in crop yield and plant growth.
PubMed: 38893909
DOI: 10.3390/ma17112646 -
Journal of Environmental Health Science... Jun 2024Society's support upon chemicals over the last few decades has led to their increased production, application and discharge into the environment. Wastewater treatment...
UNLABELLED
Society's support upon chemicals over the last few decades has led to their increased production, application and discharge into the environment. Wastewater treatment plants (WWTPs) contain a multitude of these chemicals such us; pharmaceutical compounds (PCs). Often, their biodegradability by activated sludge microorganisms is significant for their elimination during wastewater treatment. In this paper the focus is laid on two PCs carbamazepine (CBZ) and diclofenac (DCF) and their main transformation products (TPs). Laboratory degradation tests with these two pharmaceuticals using activated sludge as inoculum under aerobic conditions were performed and microbial metabolites were analyzed by liquid chromatography-mass spectrometry (LC/MS-MS). In two different Mixed liquid Suspended Solids (MLSS) concentrations the biodegradability by activated sludge of CBZ and DCF were evaluated. Also, this article proposes a decision support system to optimize the prediction process of this type of pharmacological compounds. A study and analysis of the techniques of Support Vector Machine, Random Forest, Decision Trees and Multilayer Perceptron Network is carried out to select the most reliable and accurate predictor for the decision system. There are not significant differences in the removal of DCF with 30 mg MLSS/L and 60 mg MLSS/L. DCF was better removed than CBZ in all experiments studied. The TP detected in the samples were mainly 4-OH-DCF for DCF and 10, 11 EPOXICBZ for CBZ. The results show that the best models are obtained with Random Forest and Multilayer Perceptron Network techniques, with a model fit of more than 95% for both carbamazepine and diclofenac metabolites. Obtaining a root means square errors of 0.80 µg/L for the metabolite 4-OH-DCF for DCF with the technique Random Forest and a root means square errors of 1.13 µg/L for the metabolite 10, 11 EPOXICBZ for CBZ with the Multilayer Perceptron Network technique.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40201-023-00890-x.
PubMed: 38887771
DOI: 10.1007/s40201-023-00890-x -
American Journal of Translational... 2024Formulate a gel and test its scientific efficacy for treating musculoskeletal ailments with or without phonophoresis.
OBJECTIVE
Formulate a gel and test its scientific efficacy for treating musculoskeletal ailments with or without phonophoresis.
METHODS
Gel was made from leaf extract (30:70 aqueous-methanolic). A pragmatic, community-based, double-blinded randomized clinical study (IRCT20230202057310N1) was undertaken on 380 pre-diagnosed individuals with 1st and 2nd-grade musculoskeletal injuries, divided into four parallel groups (n = 95 per group): Group I got phonophoresis-applied 10% gel. Group II got phonophoresis-applied diclofenac diethylammonium 2% gel. 10% gel was superficially massaged onto Group III. Group IV received a superficial massage with diclofenac diethylammonium 2% gel. Color, stability, pH, spreadability, beginning of pain relief, discomfort, stiffness, and activities of daily living were recorded using the Numeric Pain Rating Scale (NPRS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scale. Methods included phytochemical analysis, molecular docking, and antioxidant quantification using 2,2-diphenylpicrylhydrazyl (DPPH), nitric oxide (NO), and superoxide dismutase (SOD) tests.
RESULTS
gel worked better than diclofenac gel in phonophoresis and massage, with regard to NPRS P<0.001, WOMAC pain P<0.001, WOMAC stiffness P<0.003, and WOMAC activities of daily living (ADLs) P<0.001. There were also significant differences in pain, stiffness, and ADLs. showed significant (P<0.005-0.001) results.
CONCLUSION
gel relieved pain and inflammation in musculoskeletal injury patients. gel is natural, cheap, and easy to make. Better drug absorption may explain the effectiveness of phonophoresis.
PubMed: 38883366
DOI: 10.62347/VMJO7002