Effect of Quaternary Ammonium Surfactant on Buccal Permeation of Budesonide Film Formulation: In Silico Docking Studies

Budesonide, an immunosuppressant glucocorticosteroid generally used to ameliorate chronic inflammation. Low bioavailability due to first pass metabolism decreases its therapeutic activity. The present study focuses on the formulation of a biodegradable buccoadhesive film for improvement of buccalpermeation. Transparent buccoadhesive films were prepared by incorporating budesonide in HPMC matrix with triethalonamine as a plasticizer and a number of surfactants. Absence of the characteristic drug melting peak at 252°C in Differential Scanning Calorimetry (DSC) thermogram study confirmed almost complete amorphization of the drug to a homogenous solid-solid mixture in the film. The characteristic Fourier-Transform Infrared Spectroscopy (FTIR) peak of pure drug showed the carbonyl stretching in between 1600–1900 cm−1 and C–O stretching at 1095 cm−1. Broadening of C–O stretching and masking of carbonyl stretching confirmed the drug polymer interaction. In vitro dissolution and ex-vivo buccal tissue permeation revealed upto 72% and more than 58% respectively using surfactants upto 6 hour of study. Enhanced buccal permeability and flux were found in presence of surfactant compared to its absence. New film formulation could be developed including surfactant for improved buccal permeation with expected increased bioavailability. The in silico study confirmed about a stable interaction between drug and polymer (−3.1 kcal/mol)

Salivary Metabolomics for Oral Precancerous Lesions: A Comprehensive Narrative Review

Oral submucous fibrosis (OSMF) is a chronic, potentially malignant disorder of the oral cavity, primarily associated with the consumption of areca nut products and other risk factors. Early and accurate diagnosis of OSMF is crucial to prevent its progression to oral cancer. In recent years, the field of metabolomics has gained momentum as a promising approach for disease detection and monitoring. Salivary metabolomics, a non-invasive and easily accessible diagnostic tool, has shown potential in identifying biomarkers associated with various oral diseases, including OSMF. This review synthesizes current literature on the application of salivary metabolomics in the context of OSMF detection. The review encompasses a comprehensive analysis of studies conducted over the past decade, highlighting advancements in analytical techniques, metabolomic profiling, and identified biomarkers linked to OSMF progression. The primary objective of this review is to provide a critical assessment of the feasibility and reliability of salivary metabolomics as a diagnostic tool for OSMF, along with its potential to differentiate OSMF from other oral disorders. In conclusion, salivary metabolomics holds great promise in revolutionizing OSMF detection through the identification of reliable biomarkers and the development of robust diagnostic models. However, challenges such as sample variability, validation of biomarkers, and standardization need to be addressed before its widespread clinical implementation. This review contributes to a comprehensive understanding of the current status, challenges, and future directions of salivary metabolomics in the realm of OSMF detection, emphasizing its potential impact on early intervention and improved patient outcomes

Effect of Quaternary Ammonium Surfactant on Buccal Permeation of Budesonide Film Formulation: In Silico Docking Studies

1259-1266Budesonide, an immunosuppressant glucocorticosteroid generally used to ameliorate chronic inflammation. Low bioavailability due to first pass metabolism decreases its therapeutic activity. The present study focuses on the formulation of a biodegradable buccoadhesive film for improvement of buccalpermeation. Transparent buccoadhesive films were prepared by incorporating budesonide in HPMC matrix with triethalonamine as a plasticizer and a number of surfactants. Absence of the characteristic drug melting peak at 252C in Differential Scanning Calorimetry (DSC) thermogram study confirmed almost complete amorphization of the drug to a homogenous solid-solid mixture in the film. The characteristic Fourier-Transform Infrared Spectroscopy (FTIR) peak of pure drug showed the carbonyl stretching in between 1600–1900 cm−1 and C–O stretching at 1095 cm−1. Broadening of C–O stretching and masking of carbonyl stretching confirmed the drug polymer interaction. In vitro dissolution and ex-vivo buccal tissue permeation revealed upto 72% and more than 58% respectively using surfactants upto 6 hour of study. Enhanced buccal permeability and flux were found in presence of surfactant compared to its absence. New film formulation could be developed including surfactant for improved buccal permeation with expected increased bioavailability. The in silico study confirmed about a stable interaction between drug and polymer (−3.1 kcal/mol)

Controlled Crystallization of Acetazolamide from Aqueous Polymeric Solutions for Enhancing Dissolution Rate: Application of Statistical Moment Theory and Molecular Docking

515-521Presence of additives in crystallization process in a controlled manner can lead to different crystal morphologies which could have a favourable impact on drug dissolution rate. Four different hydrophilic polymers (methylcellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, and carboxymethyl cellulose) were used for the controlled crystallization of acetazolamide (ACZ) by solvent evaporation technique. Crystal imperfections of ACZ occurred in the lattice of growing crystal when crystallized from aqueous polymeric solution and evaluated using both the traditional Full Width at Half Maximum (FWHM) () and statistical mean value of the XRD peak width (). Crystal imperfection has brought about significant improvement in the dissolution of newly produced acetazolamide crystals. ACZ crystal produced in presence of Hydroxypropyl methylcellulose (AHPMC) showed crystal imperfection to the maximum extent and also the greatest dissolution of the drug was noticed from AHPMC compared to other crystals. Statistical mean value of the peak width of XRD data as the error-free technique has been utilized successfully for estimating crystallite properties of acetazolamide crystallized from ethanol as solvent and aqueous polymeric solution as anti-solvent. Crystallite properties using traditional Full Width Half Maxima method and the error-free Statistical Moment Analysis were compared. This controlled crystallization technique could be utilized in the design and development of formulation for improved solubility and bioavailability of the drug

Electrocatalytic reduction of CO2 to CO by a series of organometallic Re(I)-tpy complexes

A series of organometallic Re(I)(L)(CO)3Br complexes with 4'-substituted terpyridine ligands (L) has been synthesised as electrocatalysts for CO2 reduction. The complexes' spectroscopic characterisation and computationally optimised geometry demonstrate a facial geometry around Re(I) with three cis COs and the terpyridine ligand coordinating in a bidentate mode. The effect of substitution on the 4'-position of terpyridine (Re1–5) on CO2 electroreduction was investigated and compared with a known Lehn-type catalyst, Re(I)(bpy)(CO)3Br (Re7). All complexes catalyse CO evolution in homogeneous organic media at moderate overpotentials (0.75–0.95 V) with Faradaic yields of 62–98%. The electrochemical catalytic activity was further evaluated in the presence of three Brønsted acids to demonstrate the influence of the pKa of the proton sources. The TDDFT and ultrafast transient absorption spectroscopy (TAS) studies showed combined charge transfer bands of ILCT and MLCT. Amongst the series, the Re-complex containing ferrocenyl substituted terpyridine ligand (Re5) shows an additional intra-ligand charge transfer band and was probed using UV-Vis spectroelectrochemistry

Structural insights into the interactions of repositioning and known drugs for Alzheimer’s disease with hen egg white lysozyme by MM-GBSA

Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential anti-Alzheimer’s drugs, have been subjected in this study for in silico and in vitro evaluation to check their potential against protein fibrillation, which is a causative factor for multiple diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, cardiac myopathy, type-II diabetes mellitus and many others. Molecular docking and thereafter molecular dynamics (MD) simulations revealed that diltiazem, rosiglitazone, and milnacipran interact with the binding residues such as Asp52, Glu35, Trp62, and Asp101, which lie within the fibrillating region of HEWL. The MM-GBSA analysis revealed −7.86, −5.05, and −10.29 kcal/mol as the binding energy of diltiazem, rosiglitazone, and milnacipran. The RMSD and RMSF calculations revealed significant stabilities of these ligands within the binding pocket of HEWL. While compared with two reported ligands inhibiting HEWL fibrillation, milnacipran depicted almost similar binding potential with one of the known ligands (Ligand binding affinity −10.66 kcal/mol) of HEWL. Furthermore, secondary structure analyses revealed notable inhibition of the secondary structural changes with our candidate ligand; especially regarding retention of the 3/10 α-helix both by DSSP simulation, Circular dichroism, and FESEM-based microscopic image analyses. Taking further into experimental validation, all three ligands inhibited fibrillation in HEWL in simulated conditions as revealed by blue shift in Congo red assay and later expressing percentage inhibition in ThioflavinT assay as well. However, dose-dependent kinetics revealed that the antifibrillatory effects of drugs are more pronounced at low protein concentrations. Communicated by Ramaswamy H. Sarma</p

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

Measurement of the production cross section of prompt Ξ0c baryons in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum (pT) differential production cross section of the promptly-produced charm-strange baryon Ξ0c (and its charge conjugate Ξ0c¯¯¯¯¯¯) is measured at midrapidity via its hadronic decay into π+Ξ− in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The Ξ0c nuclear modification factor (RpPb), calculated from the cross sections in pp and p−Pb collisions, is presented and compared with the RpPb of Λ+c baryons. The ratios between the pT-differential production cross section of Ξ0c baryons and those of D0 mesons and Λ+c baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt Ξ0c baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p−Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The pT-integrated cross section of prompt Ξ0c-baryon production at midrapidity extrapolated down to pT = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p−Pb collisions at midrapidity