Some distance measures for pythagorean cubic fuzzy sets: Application selection in optimal treatment for depression and anxiety.

Pythagorean cubic fuzzy sets represent an advancement beyond conventional interval-valued Pythagorean sets, integrating the principles of Pythagorean fuzzy sets and interval-valued Pythagorean fuzzy sets. Given the critical significance of distance measures in real-world decision-making and pattern recognition tasks, it is noteworthy that there exists a notable gap in the literature regarding distance measures specifically tailored for Pythagorean cubic fuzzy sets. The objectives of this paper are:•To define novel generalized distance measures between Pythagorean cubic fuzzy sets (PCFSs) to tackle intricate decision-making challenges.•These novel distance measures are undergoing testing on a real-world scenario concerning the management of anxiety and depression to evaluate their effectiveness and practical application.•We have illustrated the boundedness and nonlinear characteristics inherent in these distance measures. In addition, we conduct comparative analyses with existing approaches to validate the proposed methodology, thereby providing insights into its advantages and potential applications.

Identification of potential drug molecules against fibroblast growth factor receptor 3 (FGFR3) by multi-stage computational-biophysics correlate.

The fibroblast growth factor receptor 3 (FGFR3) is warranted as a promising therapeutic target in bladder cancer as it is described in 75% of papillary bladder tumors. Considering this, the present study was conducted to use different approaches of computer-aided drug discovery (CADD) to identify the best binding compounds against the active pocket of FGFR3. Compared to control pyrimidine derivative, the study identified three promising lead structures; BDC_24037121, BDC_21200852, and BDC_21206757 with binding energy value of -14.80 kcal/mol, -12.22 kcal/mol, and -11.67 kcal/mol, respectively. The control molecule binding energy score was -9.85 kcal/mol. The compounds achieved deep pocket binding and produced balanced interactions of hydrogen bonds and van der Waals. The FGFR3 enzyme residues such as Leu478, Lys508, Glu556, Asn562, Asn622, and Asp635. The molecular dynamic (MD) simulation studies additionally validated the docked conformation stability with respect to FGFR3 with a mean root mean square deviation (RMSD) value of < 3 Å. The root mean square fluctuation (RMSF) complements the complexes structural stability and the residues showed less fluctuation in the presence of compounds. The Poisson-Boltzmann or generalized Born and surface area continuum solvation (MM/PBSA and MM/GBSA) methods revalidated compounds better binding and highlighted van der Waals energy to dominate the overall net energy. The docked stability was additionally confirmed by WaterSwap and AMBER normal mode entropy energy analyses. In a nutshell, the compounds shortlisted in this study are promising in term of theoretical binding affinity for FGFR3 but experimental validation is needed.Communicated by Ramaswamy H. Sarma.

A scale conjugate neural network approach for the fractional schistosomiasis disease system.

This study presents the numerical solutions of the fractional schistosomiasis disease model (SDM) using the supervised neural networks (SNNs) and the computational scaled conjugate gradient (SCG), i.e. SNNs-SCG. The fractional derivatives are used for the precise outcomes of the fractional SDM. The preliminary fractional SDM is categorized as: uninfected, infected with schistosomiasis, recovered through infection, expose and susceptible to this virus. The accurateness of the SNNs-SCG is performed to solve three different scenarios based on the fractional SDM with synthetic data obtained with fractional Adams scheme (FAS). The generated data of FAS is used to execute SNNs-SCG scheme with 81% for training samples, 12% for testing and 7% for validation or authorization. The correctness of SNNs-SCG approach is perceived by the comparison with reference FAS results. The performances based on the error histograms (EHs), absolute error, MSE, regression, state transitions (STs) and correlation accomplish the accuracy, competence, and finesse of the SNNs-SCG scheme.

Blockchain knowledge selection under the trapezoidal fermatean fuzzy number.

Blockchain knowledge signifies a useful fundamental knowledge to safeguard faith in transboundary transmittals for main banks and financial institutions. In the study of group decision-making, the most important issue is how to coordinate opinions from different blockchains to reach a compromise under uncertainty. To tackle uncertainties surrounding multi-attribute group decision-making (MAGDM) problems in real-life scenes, we introduce a trapezoidal fermatean fuzzy set which generalizes trapezoidal fuzzy sets and fermatean fuzzy sets. The trapezoidal fermatean fuzzy model enables the degrees of membership, abstention, and non-membership to be expressed by linguistic terms. We define the operational laws of trapezoidal fermatean fuzzy numbers, and Einstein aggregation operator based on the trapezoidal fermatean fuzzy number. This makes it more flexible and descriptive to model the attitudes of Blockchain knowledge in MAGDM applications. Since multi-input arguments are interconnected and Blockchain knowledge has a lot of options perception, we also define the TOPSIS technique to facilitate the fusion of trapezoidal fermatean fuzzy information. With the aid of the trapezoidal fermatean fuzzy-TOPSIS technique, the main goal of this research is to present a general MAGDM framework by integrating the step with the complex proportional assessment. A trapezoidal fermatean positive ideal solution always wants the maximum value of the benefit criteria and the minimum value of the cost criteria. On the other hand, the trapezoidal fermatean negative ideal solution always wants the maximum value of the cost criteria and the minimum value of the benefit criteria. An integrated trapezoidal fermatean fuzzy-TOPSIS framework is established. In the proposed decision framework, the trapezoidal fermatean fuzzy-TOPSIS method is utilized to identify the subjective weights of decision attributes, and the trapezoidal fermatean fuzzy-TOPSIS approach is used to rank alternatives. Lastly, a case study concerning blockchain knowledge assessment is presented to demonstrate that the suggested scheme is feasible and effective. Furthermore, sensitivity and comparison analyses are conducted to show the robustness and superiority of the proposed method.

Piroxicam loaded polymer hybrid microspheres based tablets with modified release kinetics: Development, characterization and in vivo evaluation.

Piroxicam (PC) is a non-steroidal anti-inflammatory drug characterized by poor aqueous solubility and reported to cause and impart crucial GIT irritation, bleeding, peptic and duodenal ulcer. Engineering of PC loaded microcapsules and its surface modification using different polymers has become the popular approach to address the said issues. The purpose of the study was to develop new PC loaded gastro-protective polymer hybrid microspheres (PHM) with subsequent conversion to tablet dosage form having modified dissolution rate and improved bioavailability. The crystallinity of the PC loaded PHM were established through powder X-ray diffraction. The optimised microspheres, PC-M1 with particle size 32±3.0µm, entrapment efficiency 83.78±2.5% and in vitro drug release 87.1±2.6% were further subjected to tablets development and in vivo evaluation. The in vitro drug release study conducted for PHM at pH media 1.2 and 6.8 demonstrated retarded and enhanced drug release rates (P<0.001) respectively. Both accelerated and real time stability studies confirmed stability of the PC loaded PHM based tablets. A substantial improvement in the drug plasma concentration 12.6±2.36 (P<0.001) was observed for the produced tablets compared to the marketed formulations.

Formulation of Aceclofenac Tablets Using Nanosuspension as Granulating Agent: An Attempt to Enhance Dissolution Rate and Oral Bioavailability.

PURPOSE: The aim of the studies was to fabricate aceclofenac (AC) tablets using nanosuspension as granulating fluid to boost its rate of in vitro dissolution and eventually its oral bioavailability. METHODS: The optimized nanosuspension with particle size of 112±2.01 nm was fabricated using HPMC 1% (w/v), PVP-K30 1% (w/v) and SLS 0.12% (w/v) at 400 watts of ultrasonication energy for 15 min duration and 3 sec pause. Then, the optimized aceclofenac nanosuspension was used as granulating fluid for aceclofenac tablets formulation. The characterization was performed using Malvern zetasizer, SEM, TEM, DSC and P-XRD. The granules were evaluated for the bulk and tapped densities, Hausner's ratio, angle of repose and their resulted values were found within limit. The prepared tablets were tested for average weight, hardness, friability, disintegration, dissolution and in vivo bioavailability in rabbits. RESULTS: The in vitro dissolution data showed the boosted rate of nanosuspension-based tablets compared to the microsuspension-based tablets. The in vivo bioavailability (in rabbits model) of aceclofenac nanosuspension-based tablets (ACN-1, ACN-2) proved an improved absorption as in comparison to the marketed formulation. The Cmax and AUC0→24 of ACN-1 and ACN-2 were 1.53-fold, 1.48-fold and 2.23-fold, 2.0-fold greater than that of the marketed drug, and were 1.74-fold, 1.68-fold and 2.3-fold, 2.21-fold greater in comparison to raw drug. CONCLUSION: This boosted in vitro and in vivo bioavailability may be attributed to reduced particle size of aceclofenac nanoformulations used in tablets. Finally, this will result in faster absorption of these fabricated tablets.

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

Fabrication and characterization of glimepiride nanosuspension by ultrasonication-assisted precipitation for improvement of oral bioavailability and in vitro α-glucosidase inhibition.

PURPOSE: We aimed to enhance the solubility, dissolution rate, oral bioavailability, and α-glucosidase inhibition of glimepiride (Glm) by fabricating its nanosuspension using a precipitation-ultrasonication approach. METHODS: Glm nanosuspensions were fabricated using optimized processing conditions. Characterization of Glm was performed using Malvern Zetasizer, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Minimum particle size and polydispersity index (PDI) values were found to be 152.4±2.42 nm and 0.23±0.01, respectively, using hydroxypropyl methylcellulose: 6 cPs, 1% w/v, polyvinylpyrrolidone K30 1% w/v, and sodium lauryl sulfate 0.12% w/v, keeping ultrasonication power input at 400 W, with 15 minutes' processing at 3-second pauses. In vivo oral bioavailability was assessed using rabbits as a model. RESULTS: The saturation solubility of the Glm nanosuspensions was substantially enhanced 3.14-fold and 5.77-fold compared to unprocessed drug in stabilizer solution and unprocessed active pharmaceutical ingredient. Also, the dissolution rate of the nanosuspensions ws substantially boosted when compared to the marketed formulation and unprocessed drug candidate. The results showed that >85% of Glm nanosuspensions dissolved in the first 10 minutes compared to 10.17% of unprocessed Glm), 42.19% of microsuspensions, and 19.94% of marketed tablets. In-vivo studies conducted in animals, i.e. rabbits, demonstrated that maximum concentration and AUC0-24 with oral dosing were twofold (5 mg/kg) and 1.74-fold (2.5 mg/kg) and 1.80-fold (5 mg/kg) and 1.63-fold (2.5 mg/kg), respectively, and compared with the unprocessed drug formulation. In-vitro α-glucosidase inhibition results showed that fabricated nanosuspensions had a pronounced effect compared to unprocessed drug. CONCLUSION: The optimized batch fabricated by ultrasonication-assisted precipitation can be useful in boosting oral bioavailability, which may be accredited to enhanced solubility and dissolution rate of Glm, ultimately resulting in its faster rate of absorption due to nanonization.

A new strategy for taste masking of azithromycin antibiotic: development, characterization, and evaluation of azithromycin titanium nanohybrid for masking of bitter taste using physisorption and panel testing studies.

BACKGROUND: The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue. PURPOSE OF STUDY: The study aimed to mask and evaluate the unpleasant bitter taste of azithro-mycin (AZ) in the dry suspension dosage form by physisorption technique. MATERIALS AND METHODS: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form. RESULTS: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation. CONCLUSION: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate.

Isolation and preliminary evaluation of Mulva Neglecta mucilage: a novel tablet binder

ABSTRACT The aim of this study was to evaluate binding potential of Mulva neglecta mucilage (MNM) with subsequent comparison to PVP K30. Eight batches of Diclofenac sodium tablets were prepared by wet granulation technique keeping different concentrations (4, 6, 8 & 10% w/w) of Mulva neglecta mucilage (extracted from leaves of Mulva neglecta) and PVP K30 as standard binder. The granules of formulated batches showed bulk density (g/mL) 0.49 ± 0.00 to 0.57 ± 0.00, tapped density (g/mL) 0.59 ± 0.01 to 0.70 ± 0.01, Carr's index 09.27 ± 0.95 to 19.65 ± 0.59, Hausner's ratio 1.12 ± 0.00 to 1.24 ± 0.01 and angle of repose 30.37 ± 2.90 °C to 36.86 ± 0.94 °C. Tablets were compressed to hardness 7.50 to 7.95 kg/cm2. The tablets showed 0.39 ± 0.02 to 0.39 ± 0.01% friability and 7:20 to 14:00 min disintegration time. Granules and post-compression evaluation revealed that parameters assessed were all found to be within the pharmacopoeial limits. The results (hardness, disintegration and dissolution) proved that Mulva neglecta mucilage has better binding capacity for preparation of uncoated tablet dosage form as compared to PVP K30. Among all the formulations, MN-1 to MN-4 showed slow release as compared to PV-1 to PV-4 and thereby Mulva neglecta mucilage exhibited satisfactory drug release phenomenon tablets of diclofenac sodium.

RESUMO O objetivo deste estudo foi avaliar o potencial de ligação de mucilagem de Mulva neglecta (MNM), com posterior comparação ao PVP K30. Oito lotes de comprimidos de diclofenaco de sódio foram preparados pela técnica de granulação úmida, mantendo diferentes concentrações (4, 6, 8 e 10% w/w) de mucilagem de Mulva neglecta (extraída de folhas de Mulva neglecta) e PVP K30 como ligante padrão. Os grânulos de lotes formulados mostraram densidade aparente (g/mL) 0.49 ± 0.00-0.57 ± 0.00, densidade compactada (g/mL) 0.59 ± 0.01-0.70 ± 0.01, índice de Carr 09.27 ± 0.95-19.65 ± 0.59, a relação de Hausner 1.12 ± 0.00-1.24 ± 0.01 e ângulo de repouso 30.37 ± 2.90 °C a 36.86 ± 0.94 °C. Os comprimidos foram prensados à dureza de 7.50-7.95 kg/cm2. Os comprimidos apresentaram 0.39 ± 0.02-0.39 ± 0.01% friabilidade e 7:20-14:00 min de tempo de desintegração. A avaliação de grânulos e pós-compressão revelou que todos os parâmetros estavam dentro dos limites da farmacopeia. Os resultados (dureza, desintegração e dissolução) provaram que a mucilagem de Mulva neglecta tem maior capacidade de ligação na preparação da forma de dosagem de comprimido não revestido em relação à PVP K30. Entre todas as formulações, MN-1 e MN-4 mostraram liberação lenta em comparação com PV-1 e PV-4 e, assim, a mucilagem de Mulva neglecta exibiu liberação do fármaco satisfatória para os comprimidos de diclofenaco de sódio.

A comparison of the effect of glitazones on serum sialic acid in patients with type 2 diabetes.

Although management of hyperglycaemia represents one of the principal treatment goals of diabetes therapy, the high incidence of cardiovascular (CV) complications in diabetes also needs effective management. Therefore, the present study was designed to determine and compare the effect of glitazones on serum sialic acid (SSA), a known risk marker for CV disease, along with fasting plasma glucose (FPG), glycohaemoglobin (HbA1-c) and blood lipids, in overweight, previously only diet-treated patients with type 2 diabetes (n=60). The study was conducted for a period of 12 months. Significant improvement in FPG and HbA1-c were shown by both rosiglitazone (p<0.003 and p<0.001, respectively) and pioglitazone (p<0.005 and p<0.001, respectively), compared with baseline, and pioglitazone showed greater beneficial effects on other parameters monitored, significantly reducing total cholesterol (TC) (p≤0.05). Both the drugs showed a decrease in SSA and no significant differences were observed between the groups. However, the decrease was significant only in the pioglitazone-treated group at month 12 (p≤0.05), compared with baseline. A significant decrease in SSA by pioglitazone indicates its greater cardioprotective effect compared with rosiglitazone.