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Pharmaceutics May 2022Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate...
Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API-polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME. The essence of the HCS is to provide an API risk categorization framework for the development of ASDs via the HME process. The proposed classification system is based on the recognition that the manufacture of crystal-free ASD using the HME process fundamentally depends on the ability of the melt temperature to reach the API's thermodynamic solubility temperature or above. Furthermore, we explored the API-polymer phase diagram as a simple tool for process design space selection pertaining to API or polymer thermal degradation regions and glass transition temperature-related dissolution kinetics limitations. Application of the HCS was demonstrated via HME experiments with two high melting temperature APIs, sulfamerazine and telmisartan, with the polymers Copovidone and Soluplus. Analysis of the resulting ASDs in terms of the residual crystallinity and degradation showed excellent agreement with the preassigned HCS class. Within AbbVie, the HCS concept has been successfully applied to more than 60 different APIs over the last 8 years as a robust validated risk assessment and quality-by-design (QD) tool for the development of HME ASDs.
PubMed: 35631630
DOI: 10.3390/pharmaceutics14051044 -
Heliyon Dec 2021This article describes the initial study on the simultaneous determination of multiclass antibiotic residues in imported and local frozen poultry specimens, including...
Detection and quantification of multiclass antibiotic residues in poultry products using solid-phase extraction and high-performance liquid chromatography with diode array detection.
This article describes the initial study on the simultaneous determination of multiclass antibiotic residues in imported and local frozen poultry specimens, including turkey gizzard and muscle tissues, and chicken muscle tissues, commonly consumed in Ogun State, Nigeria. Minced tissues were treated with phosphate buffer adjusted to pH 7 that was cleaned using C18 SPE-column (Supelclean™) cartridge. For the determination of six antibiotic residues including fluoroquinolones, sulfonamides, and macrolides, a solid-phase extraction method was used, followed by extract analysis using high-performance liquid chromatography-diode array detection (HPLC-DAD). The coefficient of determination (R) for the external standards for all the analytes ranged between 0.963 and 0.999. The limit of detection (LOD) and quantification (LOQ) ranged between 5.37 - 55.4 μg/kg, and 17.9-185 μg/kg, respectively. Enrofloxacin, sulfadimethoxine, sulfamerazine, and tylosin showed high concentration levels in the frozen poultry beyond acceptable maximum residue limits (MRLs). The six drugs considered in this study were present at higher concentrations in domestic chicken tissues than the permissible level. This suggests that farmers do not observe the cessation period before poultry birds previously treated with antibiotics are sold to consumers thus exposing them to potentially hazardous antibiotic residues.
PubMed: 34917790
DOI: 10.1016/j.heliyon.2021.e08469 -
Archiv Der Pharmazie Apr 2021New imidazolinone-based benzenesulfonamides 3a-e and 4a-e were synthesized in three steps and their chemical structures were confirmed by H NMR (nuclear magnetic...
New imidazolinone-based benzenesulfonamides 3a-e and 4a-e were synthesized in three steps and their chemical structures were confirmed by H NMR (nuclear magnetic resonance), C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas 3d and 4a were leads against hCA II in terms of K values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3-4.8 times more selective inhibitors than their corresponding analogues 3a-d in series 3, in which hydrogen was located in place of the nitro group, by considering K values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest K values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.
Topics: Acetylcholinesterase; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Cholinesterase Inhibitors; Humans; Imidazolines; Molecular Structure; Sulfonamides; Benzenesulfonamides
PubMed: 33283898
DOI: 10.1002/ardp.202000375 -
The Journal of Organic Chemistry Jul 2023A novel and efficient -arylation of sulfenamides with diaryliodonium salts for the synthesis of sulfilimines is developed. The reaction proceeds smoothly under...
A novel and efficient -arylation of sulfenamides with diaryliodonium salts for the synthesis of sulfilimines is developed. The reaction proceeds smoothly under transition-metal-free and air conditions, giving rapid access to sulfilimines in good to excellent yields via selective S-C bond formation. This protocol is scalable and exhibits a broad substrate scope, good functional group tolerance, and excellent chemoselectivity.
Topics: Metals; Sulfamerazine; Transition Elements
PubMed: 37327035
DOI: 10.1021/acs.joc.3c00961 -
Molecules (Basel, Switzerland) Jul 2023The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a...
New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.
The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.
Topics: Molecular Docking Simulation; Flurbiprofen; Ibuprofen; Enzyme Inhibitors; Sulfacetamide; Kinetics; Urease; Sulfamerazine; Canavalia; Structure-Activity Relationship; Sulfanilamide; Sulfonamides; Molecular Structure
PubMed: 37513261
DOI: 10.3390/molecules28145389 -
Chemosphere Dec 2021Cu(II) is generally considered to be a poor activator for PMS decomposition, thus the potential impact of trace Cu(II) on PMS induced oxidation of typical pollutants is...
Cu(II) is generally considered to be a poor activator for PMS decomposition, thus the potential impact of trace Cu(II) on PMS induced oxidation of typical pollutants is always overlooked. In this study, we reported that trace Cu(II) could significantly promote PMS induced degradation of four selected sulfonamide antibiotics (SAs), namely, sulfamehoxazole (SMX), sulfathiazole (STZ), sulfamerazine (SMZ), and sulfamonomethoxine (SMM). Different from conventional PMS-induced oxidation process, high-valent Cu(III) was ascertained as the primary reactive intermediate for SAs degradation, which was confirmed by raman tests and electron paramagnetic resonance (EPR). High concentrations of Cu(II) or PMS were beneficial to degradation of the selected contaminants. In PMS/Cu(II) oxidation system, all the selected SAs could undergo several different degradation pathways including continuous oxidation of aniline group, hydroxylation and S-N bond cleavage. In particular, for six-membered SAs, such as SMZ and SMM, a SO extrusion pathway was also detected. The potential mechanism for Cu(III) formation was also proposed, which was believed to be highly related to the nature of the SAs. Hydroxylamine-SAs (N-OH-SAs), generated from direct PMS oxidation of SAs, was deduced as the "promoter" for the whole oxidation process. And the generation of Cu(III) was likely to proceed through the interaction between PMS and Cu(I), which possibly derived from the reduction of Cu(II) by N-OH-SAs. The results obtained in this study validated the contribution of Cu(III) to the elimination of pollutants and expanded our understanding of the oxidation process of PMS in the presence of trace amounts of Cu(II).
Topics: Anti-Bacterial Agents; Oxidation-Reduction; Peroxides; Sulfonamides; Water Pollutants, Chemical
PubMed: 34198061
DOI: 10.1016/j.chemosphere.2021.131329 -
The Science of the Total Environment Nov 2023As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and...
As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and non-biodegradable MPs in the aquatic environment, the adsorption behaviors of polyamide (PA) and polylactic acid (PLA) towards two sulfonamide antibiotics (SAs) were investigated. Both chemical and photo-aging were used to handle the virgin MPs. Compared with PA, PLA was aged more drastically, showing the obvious grooves, notches and folds. However, due to the higher temperature during chemical aging, the tiny KPLA (PLA aged by KSO) particles were agglomerated and the specific surface area was reduced to nearly 95 %. For PA, the oxidation of chemical aging was stronger than photo-aging. After aging, the hydrophilicity and polarity of MPs increased. In the adsorption experiments, the adsorption capacity of PA towards SAs was 1.7 times higher than that of PLA. Aging process enabled the adsorption capacity of PLA increased 1.22-3.18 times. Overall, the adsorption capacity of sulfamethoxazole (SMX) by both MPs was superior to sulfamerazine (SMR). These results would help to understand the carrier effects and potential ecological risks of MPs towards co-existing contaminants.
PubMed: 37607636
DOI: 10.1016/j.scitotenv.2023.166452 -
Chemosphere Feb 2022The effects of and main contributors in rhizosphere and plant species on the degradation of sulfonamides (SAs) in constructed wetland (CW) models for the treatment of...
The effects of and main contributors in rhizosphere and plant species on the degradation of sulfonamides (SAs) in constructed wetland (CW) models for the treatment of domestic wastewater are currently unclear. To investigate the degradation and key rhizosphere factors of mixed SAs with sulfadiazine (SDZ), sulfapyridine (SPD), sulfamerazine (SMZ1), sulfamethazine (SMZ2), and sulfamethoxazole (SMX) at millimeter distances from the root surface, a multi-interlayer rhizobox experiment planted with Cyperus alternifolius, Juncus effusus, Cyperus papyrus, and an unvegetated control was conducted. There was a higher O saturation and dissolved organic carbon (DOC) content and a lower SA content in the rhizosphere and near/moderate-rhizosphere (0-3 and 3-8 mm from rhizosphere) than the far/non-rhizosphere (8-40 and 40-90 mm from rhizosphere). Bacterial abundance and community composition was indicative of the microbial degradation of SAs. Both the O and DOC contents promoted total bacterial abundance in different zones from CW rhizoboxes. The relative abundance of the most dominant bacteria was significantly correlated with O, DOC, and SAs, except SMX, which also indicates other dissipation processes for SMX in the rhizosphere. Furthermore, more metabolites and aerobic SA-degrading bacteria were observed in the rhizosphere and near/moderate-rhizosphere than in the far/non-rhizosphere zones, suggesting that the effect of O in the rhizosphere is important in the degradation of SAs in CWs.
Topics: Dissolved Organic Matter; Rhizosphere; Sulfonamides; Wastewater; Wetlands
PubMed: 34626651
DOI: 10.1016/j.chemosphere.2021.132487 -
The Science of the Total Environment Mar 2021Compared to surface application, manure subsurface injection significantly reduces transport of manure-associated antibiotics via surface runoff. However, the...
Compared to surface application, manure subsurface injection significantly reduces transport of manure-associated antibiotics via surface runoff. However, the environmental fate of antibiotics in manure injection slits is unknown. A field investigation was conducted to monitor distribution and dissipation of pirlimycin, tylosin, chlortetracycline, and sulfamerazine in soil following either surface application or subsurface injection of liquid dairy manure. A simulated rainfall was conducted on days 0, 3, and 7 after manure application. Soil samples were collected before, on the day of, and 5, 14, 60, and 180 days after the simulated rainfall. Around an hour after manure application, antibiotic concentrations in injection slits were 4-49 and 4-26 times higher than those outside the slits and in surface application plots, respectively. Antibiotics concentrated in the injection slits for an extended time with limited horizontal and vertical movement, exposing the microbial community inside the slits to an elevated level of antibiotics. Dissipation of antibiotics was the fastest during the first 14 d after manure application before slowing down. There were no significant differences in antibiotic dissipation patterns in soils amended with manure using two application methods. Although the half-lives ranged from 3-11 d for pirlimycin, 3-10 d for sulfamerazine, 5-12 d for tylosin, and 3-21 day for chlortetracycline; pirlimycin, sulfamerazine, and tylosin remained detectable in soil even 180 d after the single manure application, indicating that soils could be a long-term source for antibiotics to the surrounding environment. Overall, in addition to resulting in less surface runoff of antibiotics from the fields, manure subsurface injection can also retain antibiotics in the injection slits and limit their movement overtime. However, more studies are needed to better understand if elevated levels of antibiotics, nutrients, organic matter, and water would result in "hot zones" for antibiotic resistance development in the manure subsurface injected fields.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Manure; Soil; Tylosin
PubMed: 33172639
DOI: 10.1016/j.scitotenv.2020.143431 -
Molecules (Basel, Switzerland) Jun 2021Rapid chromatographic procedure for quantification of five sulfonamides in medicated feeds are proposed. Satisfactory separation of sulfonamides from medicated feeds was...
Rapid chromatographic procedure for quantification of five sulfonamides in medicated feeds are proposed. Satisfactory separation of sulfonamides from medicated feeds was achieved using a Zorbax Eclipse XDB C18 column (4.6 × 150 mm, 5 µm particle size) with a micellar mobile phase consisting of 0.05 M sodium dodecyl sulphate, 0.02 M phosphate buffer, and 6% propan--ol (pH 3). UV quantitation was set at 260 nm. The proposed procedure allows the determination of sulfaguanidine, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole in medicated feeds for pigs and poultry. Application of the proposed method to the analysis of five pharmaceuticals gave recoveries between 72.7% to 94.7% and coefficients of variations for repeatability and reproducibility between 2.9% to 9.8% respectively, in the range of 200 to 2000 mg/kg sulfonamides in feeds. Limit of detection and limit of quantification were 32.7-56.3 and 54.8-98.4 mg/kg, respectively, depending on the analyte. The proposed procedure for the quantification of sulfonamides is simple, rapid, sensitive, free from interferences and suitable for the routine control of feeds. In the world literature, we did not find the described method of quantitative determination of sulfonamides in medicated feeds with the use of micellar liquid chromatography.
Topics: Animal Feed; Animals; Micelles; Sulfonamides; Swine
PubMed: 34206391
DOI: 10.3390/molecules26133791