Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolutio

Synthesis of N-substituted acetamide derivatives of azinane-bearing 1,3,4-oxadiazole nucleus and screening for antibacterial activity

Purpose: To synthesize some acetamide derivatives bearing azinane and 1,3,4-oxadiazole heterocyclic cores and to evaluate their antibacterial potentials.Methods: Ethyl piperidin-4-carboxylate (2) was converted to ethyl 1-[(4-chlorophenyl)sulfonyl]piperidin- 4-carboxylate (3), 1-[(4-chlorophenyl)sulfonyl]piperidin-4-carbohydrazide (4) and 5-[1-(4-chlorophenylsulfonyl)-4-piperidinyl]-1,3,4-oxadiazol-2-thiol (5) using three consecutive steps. The target molecules, 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(substituted)-2-acetamoyl]thio]}-1,3,4- oxadiazole (8a-n) were synthesized by stirring 5 and N-aryl-2-bromoacetamides (7a-n) in an aprotic polar solvent. The structures were corroborated by infrared (IR), electron impact mass spectrometry (EIMS) and proton/carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopic techniques. The evaluation of antibacterial activity was based on the effect on the increase in absorbance of the broth medium due to log phase microbial growth.Results: Compound 8g bearing a 2-methylphenyl group was the most the active growth inhibitor of Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis bacterial strains with minimum  inhibitory concentrations (MIC) of 10.63±0.97, 10.31±1.00, 10.45 ± 0.94 and 11.77±5.00 μM, respectively. Ciprofloxacin was used as reference standard.Conclusion: All the synthesized compounds are moderate inhibitors but relatively more active against Gram-negative bacterial strains. 5-{1-[(4- Chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(2-methylphenyl)-2- acetamoyl]thio]}-1,3,4-oxadiazole (8g) is the most active growth inhibitor of all the strains except Staphylococcus aureus.Keywords: 1,3,4-Oxadiazole, Acetamides, Antibacterial activity, Piperidin

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Missed opportunity for timely intervention to prevent a life-threatening event

The LifeVest wearable cardioverter-defibrillator (WCD; ZOLL Medical Corp, Pittsburgh, PA) has been approved by the US Food and Drug Administration for use with select patients who are at risk for sudden cardiac arrest. However, one of its lesser-emphasized features is the ability to detect asystole and severe bradycardic events that can help in the early identification of patients in need of pacing. Here, we describe the case of a 71-year-old man who had advanced atrioventricular (AV) block lasting 10 seconds documented by the LifeVest system and discuss some of the features of the LifeVest that can be optimized to expedite the care of these patients

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol

Purpose: The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release. Methods: Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels. Results: The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively). Conclusions: As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT

Amikacin-Loaded Chitosan Hydrogel Film Cross-Linked with Folic Acid for Wound Healing Application

Purpose: Numerous carbohydrate polymers are frequently used in wound-dressing films because they are highly effective materials for promoting successful wound healing. In this study, we prepared amikacin (AM)-containing hydrogel films through the cross-linking of chitosan (CS) with folic acid along with methacrylic acid (MA), ammonium peroxodisulfate (APS), and methylenebisacrylamide (MBA). In the current studies, an effort has been made to look at the possibilities of these materials in developing new hydrogel film wound dressings meant for a slow release of the antibiotic AM and to enhance the potential for wound healing. Methods: Free-radical polymerization was used to generate the hydrogel film, and different concentrations of the CS polymer were used. Measurements were taken of the film thickness, weight fluctuation, folding resistance, moisture content, and moisture uptake. HPLC, FTIR, SEM, DSC, and AFM analyses were some of the different techniques used to confirm that the films were successfully developed. Results: The AM release profile demonstrated regulated release over a period of 24 h in simulated wound media at pH 5.5 and 7.4, with a low initial burst release. The antibacterial activity against gram-negative bacterial strains exhibited substantial effectiveness, with inhibitory zones measuring approximately 20.5 &plusmn; 0.1 mm. Additionally, in vitro cytocompatibility assessments demonstrated remarkable cell viability, surpassing 80%, specifically when evaluated against human skin fibroblast (HFF-1) cells. Conclusions: The exciting findings of this study indicate the promising potential for further development and testing of these hydrogel films, offering effective and controlled antibiotic release to enhance the process of wound healing

Effect of tool pin profiles on defects formation during friction stir welding of AA 6082-T6 straight-pipes-butt-weld joints

Friction stir welding (FSW) has emerged as a solid-state bonding technique widely used due to the efficacy in welding challenging materials and various joint configurations. However, welding of the pipes present unique challenges due to the limited contact surface area between the tool and the pipes. In the current study, FSW was employed on the AA 6082-T6 aluminium (Al) straight-pipe-butt-weld (SPBW) joints using high-speed steel tools with different tool pin profiles (i.e., plane cylindrical, tapered cylindrical, threaded cylindrical, and square pin profiles) in flat position (i.e. workpiece rotates). A series of single-pass and two-pass FSW runs were performed to weld the AA 6082-T6 pipes, and their effects were systematically investigated on defect formation. Microstructural examination of samples welded with threaded cylindrical pin revealed larger tunnel defect compared to other pin profiles. Additionally, defects such as kissing bonds and lack of fusion were also found in the samples. Interestingly, a very small tunnel defect was observed in the sample welded with square pin tool. Consequently, the tensile test of this sample exhibited superior tensile strength and weld joint efficiency compared to other pin profiles. Microhardness testing revealed that the sample welded with a tapered cylindrical tool exhibited highest microhardness, while the two-pass sample using a threaded pin exhibited the lowest hardness