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Molecules (Basel, Switzerland) Jan 2024Arbidol hydrochloride is an antiviral product widely used in Russia and China for the treatment of, among other diseases, influenza. In recent years, it has turned out...
DSC, TGA-FTIR and FTIR Assisted by Chemometric Factor Analysis and PXRD in Assessing the Incompatibility of the Antiviral Drug Arbidol Hydrochloride with Pharmaceutical Excipients.
Arbidol hydrochloride is an antiviral product widely used in Russia and China for the treatment of, among other diseases, influenza. In recent years, it has turned out to be highly effective against COVID-19. However, there is little knowledge about its physicochemical properties and its behavior in the presence of various pharmaceutical excipients, which could be useful in the development of new preparations by increasing its solubility and bioavailability. For this reason, binary mixtures composed of arbidol hydrochloride and selected pharmaceutical excipients such as chitosan, polyvinylpyrrolione K-30 and magnesium stearate were prepared and subjected to differential scanning calorimetry (DSC), thermogravimetry combined with Fourier transform infrared spectrometry (TGA-FTIR) and Fourier transform infrared spectrometry (FTIR) analyses. In order to obtain clarity in the interpretation of the outcomes, chemometric calculations with factor analysis (FA) were used. Additionally, a powder X-ray diffraction (PXRD) and an intrinsic dissolution rate study were performed for arbidol hydrochloride itself and in the presence of excipients. As a result of the study, it was revealed that arbidol hydrochloride may undergo polymorphic transformations and be incompatible with chitosan and magnesium stearate. However, mixing arbidol hydrochloride with polyvinylpyrrolidone K-30 guarantees the obtaining of durable and safe pharmaceutical preparations.
Topics: Calorimetry, Differential Scanning; Chemometrics; Chitosan; Excipients; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Factor Analysis, Statistical; Hydrochloric Acid; Antiviral Agents; Indoles; Sulfides
PubMed: 38202847
DOI: 10.3390/molecules29010264 -
Pharmaceutics Aug 2023The main objective of this study consists in establishing the influence of the intergranular superdisintegrant on the specific properties of drotaverine hydrochloride...
The main objective of this study consists in establishing the influence of the intergranular superdisintegrant on the specific properties of drotaverine hydrochloride fast-dissolving granules (DROT-FDGs) and orodispersible tablets (DROT-ODTs). The orodispersible tablets were obtained by the compression of the FDGs and excipient mixture with an eccentric tableting machine. To develop DROT-ODTs, two types of superdisintegrant excipients in different concentrations (water-soluble soy polysaccharides (SSP) (1%, 5%) and water-insoluble soy polysaccharides-Emcosoy STS IP (EMCS) (1%, 3%, 5%)) were used, resulting in five formulations (D1-D5). The DROT-FDGs and the DROT-ODTs were subjected to pharmacotechnical and analytical evaluation. All the orodispersible tablets obtained respect the quality requirements in terms of friability (less than 1%), crushing strength (ranging between 52 N for D2 and 125.5 N for D3), and disintegration time (<180 s). The in vitro release of drotaverine from ODTs showed that all formulations presented amounts of active substance released greater than 85% at 10 min. The main objective, developing 30 mg DROT-ODTs for children aged between 6 and 12 years by incorporating the API in FDGs, was successfully achieved.
PubMed: 37631361
DOI: 10.3390/pharmaceutics15082147 -
PloS One 2023This crossover randomized controlled trial (RCT) investigated differences in short-term entero-endocrine response to a mixed-meal tolerance test preceded by nutrient... (Randomized Controlled Trial)
Randomized Controlled Trial
The entero-endocrine response following a mixed-meal tolerance test with a non-nutritive pre-load in participants with pre-diabetes and type 2 diabetes: A crossover randomized controlled trial proof of concept study.
INTRODUCTION
This crossover randomized controlled trial (RCT) investigated differences in short-term entero-endocrine response to a mixed-meal tolerance test preceded by nutrient sensing between participants with pre-diabetes (pre-T2D) and type 2 diabetes (T2D). Additionally, differences in gut and oral microbiome composition between participants with a high and low entero-endocrine response were investigated.
RESEARCH DESIGN AND METHODS
Ten participants with pre-T2D and ten with T2D underwent three test days with pre-loads consisting of either swallowing water (control), or rinsing with a non-nutritive sweetener solution, or swallowing the sweetener solution before a mixed-meal tolerance test. Blood glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, glucose, insulin and peptide YY (PYY) were determined at t = -20, 0, 15, 30, 60, 120 and 240 minutes. The composition of the oral and gut microbiome at baseline were also determined.
RESULTS
The entero-endocrine response differed by pre-loads, e.g. a lower PYY response after swallowing the non-nutritive sweetener (-3585.2pg/mL [95% CI: -6440.6; -729.8]; p = 0.01). But it also differed by T2D status, e.g. a higher glucose, glucagon and PYY response was found in participants with T2D, compared to those with pre-T2D. Evidence for associations between the oral and gut microbiome composition and the entero-endocrine response was limited. Still, the level of entero-endocrine response was associated with several oral microbiome measures. Higher oral anterior α-diversity was associated with a lower PYY response (e.g. Inverse Simpson index -1357pg/mL [95% CI -2378; -336; 1.24]), and higher oral posterior α-diversitywith a higher GIP response (e.g. Inverse Simpson index 6773pg/mL [95% CI 132; 13414]) in models adjusted for sex, age and T2D status.
CONCLUSIONS
Non-nutritive pre-loads influence the entero-endocrine response to a mixed-meal, and this effect varies based on (pre-)T2D status. The entero-endocrine response is likely not associated with the gut microbiome, and there is limited evidence for association with the α-diversity of the oral microbiome composition.
TRIAL REGISTRATION
Trial register: Netherlands Trial Register NTR7212, accessible through International Clinical Trials Registry Platform: ICTRP Search Portal (who.int).
Topics: Humans; Child, Preschool; Prediabetic State; Glucagon; Non-Nutritive Sweeteners; Proof of Concept Study; Diabetes Mellitus, Type 2; Excipients; Gastric Inhibitory Polypeptide; Glucose
PubMed: 37624823
DOI: 10.1371/journal.pone.0290261 -
Pharmaceutics Sep 2023Several studies have demonstrated the feasibility of in situ co-crystallization in different pharmaceutical processes such as spray drying, hot melt extrusion, and...
Several studies have demonstrated the feasibility of in situ co-crystallization in different pharmaceutical processes such as spray drying, hot melt extrusion, and fluidized bed granulation (FBG) to produce co-crystal-in-excipient formulations. However, no previous studies have examined such a one step in situ co-crystallization process for co-crystal formulations where the coformer is a polymer. In the current study, we explored the use of FBG to produce co-crystal granules of dapsone (DAP) and different molecular weight polyethylene glycols (PEGs). Solvent evaporation (SE) was proven to generate DAP-PEGs co-crystals at a particular weight ratio of 55:45 / between DAP and PEG, which was subsequently used in FBG, using microcrystalline cellulose and hydroxypropyl methyl cellulose as filler excipient and binder, respectively. FBG could generate co-crystals with higher purity than SE. Granules containing DAP-PEG 400 co-crystal could be prepared without any additional binder. DAP-PEG co-crystal granules produced by FBG demonstrated superior pharmaceutical properties, including flow properties and tableting properties, compared to DAP and DAP-PEG co-crystals prepared by SE. Overall, in situ co-crystallization via FBG can effectively produce API-polymer co-crystals and enhance the pharmaceutical properties.
PubMed: 37765298
DOI: 10.3390/pharmaceutics15092330 -
Nature Communications Aug 2023In vertebrate vision, early retinal circuits divide incoming visual information into functionally opposite elementary signals: On and Off, transient and sustained,...
In vertebrate vision, early retinal circuits divide incoming visual information into functionally opposite elementary signals: On and Off, transient and sustained, chromatic and achromatic. Together these signals can yield an efficient representation of the scene for transmission to the brain via the optic nerve. However, this long-standing interpretation of retinal function is based on mammals, and it is unclear whether this functional arrangement is common to all vertebrates. Here we show that male poultry chicks use a fundamentally different strategy to communicate information from the eye to the brain. Rather than using functionally opposite pairs of retinal output channels, chicks encode the polarity, timing, and spectral composition of visual stimuli in a highly correlated manner: fast achromatic information is encoded by Off-circuits, and slow chromatic information overwhelmingly by On-circuits. Moreover, most retinal output channels combine On- and Off-circuits to simultaneously encode, or multiplex, both achromatic and chromatic information. Our results from birds conform to evidence from fish, amphibians, and reptiles which retain the full ancestral complement of four spectral types of cone photoreceptors.
Topics: Male; Animals; Retina; Chickens; Retinal Cone Photoreceptor Cells; Brain; Excipients; Mammals
PubMed: 37652912
DOI: 10.1038/s41467-023-41032-z -
Pharmaceuticals (Basel, Switzerland) Oct 2023Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane...
Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane (PU)-based hydrogels with various excipients (PEG, PVP, HPC, and essential oil) were prepared and loaded with MX. Rheological investigations were carried out on the PU-based formulations in various shear regimes, and their viscoelastic characteristics were determined. The average size of the PU micelles was 35.8 nm at 37 °C and slightly increased at 37 nm in the presence of MX. The zeta potential values of the hydrogels were between -10 mV and -11.5 mV. At pH = 6 and temperature of 37 °C, the formulated PU-based hydrogels loaded with MX could deliver significant amounts of the active substance, between 60% and 80% over 24-48 h and more than 90% within 2 weeks. It was found that anomalous transport phenomena dominated MX's release mechanism from the PU-based networks. The results are encouraging for further studies aiming to design alternative carriers to commercial dosage forms of nonsteroidal anti-inflammatory drugs.
PubMed: 38004376
DOI: 10.3390/ph16111510 -
Clinical Infectious Diseases : An... Jan 2024The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).
BACKGROUND
The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population.
METHODS
Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity.
RESULTS
A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild.
CONCLUSIONS
In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate.
CLINICAL TRIALS REGISTRATION
Clinicaltrials.gov NCT03699839.
Topics: Adult; Humans; Influenza Vaccines; Influenza, Human; Switzerland; Antibodies, Viral; Influenza A Virus, H1N1 Subtype; Polysorbates; Squalene; Adjuvants, Immunologic; Hemagglutination Inhibition Tests; Organ Transplantation
PubMed: 37584344
DOI: 10.1093/cid/ciad477 -
International Journal of Pharmaceutics Mar 2024Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may...
Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may negatively affect the release control mechanism of pellets, and subunits may not be readily available after intake. Application of a cushioning layer to the starting units is here proposed as a strategy to obtain tablets with satisfactory mechanical strength, rapid disintegration and maintenance of the expected release profile of individual subunits while avoiding the use of mixtures of pellets and excipients to promote compaction and limit the impact of the forces involved. Cushion-coating with PEG1500, a soft and soluble material, was proved feasible provided that the processing temperature was adequately controlled. Cushioned gastro-resistant pellets were shown to consolidate under relatively low compaction pressures, which preserved their inherent release performance after tablet disintegration. Adhesion problems associated with the use of PEG1500 were overcome by applying an outer Kollicoat® IR film. Through design of experiment (DoE), robustness of the proposed approach was demonstrated, and the formulation as well as tableting conditions were optimized. The tableted cushion-coated pellet systems manufactured would allow a relatively high load of modified-release units to be conveyed, thus setting out a versatile and scalable approach to oral administration of multiple-unit dosage forms.
Topics: Excipients; Delayed-Action Preparations; Drug Implants; Tablets; Administration, Oral
PubMed: 38316318
DOI: 10.1016/j.ijpharm.2024.123874 -
International Journal of Molecular... Aug 2023Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1β, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin.
Topics: Humans; Tumor Necrosis Factor-alpha; Eczema; Skin; Inflammation; Pruritus; Cytokines; Excipients
PubMed: 37629159
DOI: 10.3390/ijms241612979 -
Anais Da Academia Brasileira de Ciencias 2023Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been...
Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of β- cyclodextrins, methyl-β-cyclodextrin (M-β- cyclodextrins), and (2-hydroxypropyl)-β-cyclodextrin (HP-β-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of β-cyclodextrins and M-β-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-β-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that β-cyclodextrins, M-β-cyclodextrins, and HP-β-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins' efficacy and adverse effects is essential for better accepting their use in medicine.
Topics: Rats; Animals; beta-Cyclodextrins; Cyclodextrins; 2-Hydroxypropyl-beta-cyclodextrin; Energy Metabolism
PubMed: 37531490
DOI: 10.1590/0001-3765202320201783