Synthesis, Characterization, Biological Evaluation, and In Silico Studies of Imidazolium-, Pyridinium-, and Ammonium-Based Ionic Liquids Containing n-Butyl Side Chains.

Ionic liquids (ILs) have emerged as active pharmaceutical ingredients because of their excellent antibacterial and biological activities. Herein, we used the green-chemistry-synthesis procedure, also known as the metathesis method, to develop three series of ionic liquids using 1-methyl-3-butyl imidazolium, butyl pyridinium, and diethyldibutylammonium as cations, and bromide (Br-), methanesulfonate (CH3SO3-), bis(trifluoromethanesulfonyl)imide (NTf2-), dichloroacetate (CHCl2CO2-), tetrafluoroborate (BF4-), and hydrogen sulfate (HSO4-) as anions. Spectroscopic methods were used to validate the structures of the lab-synthesized ILs. We performed an agar well diffusion assay by using pathogenic bacteria that cause various infections (Escherichia coli; Enterobacter aerogenes; Klebsiella pneumoniae; Proteus vulgaris; Pseudomonas aeruginosa; Streptococcus pneumoniae; Streptococcus pyogenes) to scrutinize the in vitro antibacterial activity of the ILs. It was established that the nature and unique combination of the cations and anions were responsible for the antibacterial activity of the ILs. Among the tested ionic liquids, the imidazolium cation and NTf2- and HSO4- anions exhibited the highest antibacterial activity. The antibacterial potential was further investigated by in silico studies, and it was observed that bis(trifluoromethanesulfonyl)imide (NTf2-) containing imidazolium and pyridinium ionic liquids showed the maximum inhibition against the targeted bacterial strains and could be utilized in antibiotics. These antibacterial activities float the ILs as a promising alternative to the existing antibiotics and antiseptics.

A comparative evaluation of antibacterial activities of imidazolium-, pyridinium-, and phosphonium-based ionic liquids containing octyl side chains.

Antibacterial activity is an essential property of ionic liquids. In this work, a comprehensive study has been performed on the antibacterial activity of ionic liquids to be utilized for further research and applications. Eighteen ionic liquids viz. Octyl Imidazolium, octyl Pyridinium, quaternary phosphonium-based cations containing bromide, sodium methane sulphonates, bis(trifluoromethane sulfonyl) imide, dichloroacetate, tetrafluoroborate, hydrogen sulfate were prepared and characterized with the help of different spectroscopic techniques. All these samples of ionic liquids were tested for their antibacterial activity against the most commonly occurring bacteria in the environment, i.e., Enterobacter aerogenes (E. aerogenes), Proteus vulgaris (P. vulgaris), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Streptococcus pyogenes (S. pyogenes). Most of the ionic liquids show good antibacterial properties, and imidazolium-based ionic liquids were even more antibacterial as compared to positive control. It was observed that a unique combination of cation and anion is essential to achieve desired antibacterial properties. The mechanism of antibacterial activity was further investigated using density functional theory calculations. A good correlation was found between experimental and theoretical studies.

Formulation of instant disintegrating buccal films without using disintegrant: An in-vitro study.

The current study was conducted to fabricate Metoclopramide HCL (MCH) and Sumatriptan succinate (SS) instant release buccal films (IRBF) without using any super disintegrant. The solvent casting method was used for the preparation of IRBFs and prepared IRBFs were physicochemically evaluated. Spectrophotometric analysis was done to determine the lambda max followed by the linearity determination of both drugs. Different concentrations such as 100, 125, and 150mg of hydrophilic polymer (HPMC E5) were employed but the concentration of glycerol was variable. Comparatively better results were observed for the formulation with 150mg of HPMC E5 and 30% glycerol. Formulated IRBFs showed good tensile strength with a mean disintegration time of 12.4-28.4 seconds and rapid dissolution with more than 50% drug release within 2 minutes. It was concluded that the chosen combination of polymers was appropriate for the fabrication of MCH and SS buccal strips.

Fabrication of polyvinyl alcohol based fast dissolving oral strips of sumatriptan succinate and metoclopramide HCL.

Migraine is a throbbing condition, usually associated with nausea and vomiting and requires concurrent administration of anti-migraine along with anti-emetic therapy. The current study was undertaken with an aim to fabricate fast dissolving oral strips (FDOSs) containing Sumatriptan succinate (anti-migraine) and Metoclopramide HCl (anti-emetic) in combination without involving any superdisintegrant. Hydrophilic polymer polyvinyl alcohol (PVA) was used alone with three concentrations of 100, 125, and 150 mg using variable concentrations of glycerol. The solvent casting technique was employed to formulate FDOSs and were evaluated for surface morphology, mechanical properties, surface pH, % moisture content, disintegration time (DT), total dissolving time (TDT), drug contents, and dissolution profile. PVA (150 mg) with 5% glycerol concentration gave best formulation results. FDOSs have exhibited good tensile strength with smooth and uniform surface morphology. DT was ranged from 7.7 to 28 s; while TDT was from 26.4 to 77.6 s. Both polymer and plasticizer concentrations were found to be influencing the characteristics of the strips. Dissolution studies were carried out in distilled water for 15 min and all the formulations have shown released more than 50% drug within first 2 min thereby highlighting the usefulness of FDOSs for the delivery of both drugs in combination significantly. Optimized combination of ingredients was found to be suitable for the formulation of FDOSs for simultaneous delivery of Metoclopramide HCl and Sumatriptan succinate.

Outcome of inadvertent high dose BCG administration in newborns at a tertiary care hospital, Karachi- Case series.

Bacillus Calmette-Guérin (BCG) vaccine is given to newborns soon after birth. BCG vaccine overdose has been rarely reported. Here we report the outcome of newborns who accidently received high dose BCG at a tertiary care hospital, Karachi. We reviewed records of 26 newborns, who accidentally received intradermal high dose BCG, used for the treatment of urinary bladder cancers and 80 times higher dose than the BCG used for routine vaccination. The incident happened from 14-16th April, 2016 at Aga Khan University Hospital, Karachi. Analysis was carried out using SPSS. A total of 23/26(88.5%) newborns were followed for atleast 3 months and 11/26 (42.3%) were followed for atleast one year. 13/26 (50%) were male. All 26 patients were prescribed isoniazid and rifampicin for 3 months. 3/26 (11.5%) were lost to follow-up before completion of anti-tuberculous drugs (ATT). Lesions at the BCG site were observed in 16/26 (61.5%) infants, of which 15 (93.8%) had a papule, 3 (18.8%) developed a pustule, 3 (18.8%) had skin induration and 2 (12.5%) had skin erythema. Axillary lymphadenopathy was observed in 1/26 (3.8%) patient. Coagulation was deranged in 3/26 (11.5%) of babies. Intracranial bleeding was observed in 1/26 (3.8%) case. Localized skin lesions were the most common adverse events. None of them developed clinical tuberculosis. Chemoprophylaxis for inadvertent high dose BCG administration should be given for atleast 3 months. Furthermore, vigilant follow-up, transparency and disclosure are the vital steps in the management of any medical error.

Reliability of Ultrasound for the Detection of Rheumatoid Arthritis.

The aim of this review article was to investigate the pooled sensitivity and specificity of musculoskeletal ultrasound (MSUS) for the detection of synovitis and early bone erosion in the small joint in rheumatoid arthritis (RA). In addition, investigate the pooled sensitivity and specificity of Power Doppler ultrasonography (PDUS) for the detection of synovial hypervascularity in small joints in RA. A systematic literature search of PubMed, Wiley online library, Google Scholar, Research gate, E-book, BioMed Central, the Journal of Rheumatology and Springer Link were investigated from 2001 to 2017. Original researches related to the article written in English including RA, synovitis, bone erosion, grayscale, and PDUS were included in this study. The sample size, study design, sensitivity, and specificity were analyzed. The review summarizes the value of MSUS for the detection of RA as it is the first choice of modality. Results show the acceptable reliability of US for the diagnosis of early bone erosions, synovitis, and synovial hypervascularity.

Synthesis, spectral characterization and enzyme inhibition studies of different chlorinated sulfonamides.

Sulfonamides are adherent to a biologically dynamic category of compounds and are under consideration of many organic synthetic researches to synthesize pharmacologically important compounds. In this demonstrated research work, a benignant series of chlorinated sulfonamides were synthesized and screened against different enzymes. These various chlorinated sulfonamides (3a-i) were set up by pairing of different substituted anilines (2a-i) with 4-chlorobenzenesulfonyl chloride (1) under basic pH in an aqueous media. The structures of the synthesized chlorinated sulfonamides were furnished by 1H-NMR, IR & EI-MS. The different enzymes used for the evaluation of bioactivity of all the synthesized compounds were urease, butyrylcholinesterase (BChE) and lipoxygenase (LOX). All the compounds exhibited good inhibitory activities against these enzymes but the strong activity was shown against BChE and hence can be employed for discovery of 'lead' compounds against Alzheimer's disease (AD).