DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS OF MEMANTINE HYDROCHLORIDE-A REMEDY FOR ALZHEIMER’S DISEASE

Objective: The study is directed towards the development of an orally disintegrating drug delivery system of memantine hydrochloride which can be commercially exploited for the well-being of society for the treatment of Alzheimer’s disease, which is a most common form of dementia. Methods: Orally disintegrating immediate-release tablets of memantine hydrochloride were prepared and optimized for disintegration time and in vitro drug release. The top spray granulation method was used for the preparation of granules. Subsequently, these granules were compressed to tablets. The levels of diluent, disintegrant and taste-masking agents were optimized using the design of experiments. The resulting tablets were evaluated for disintegration time and in vitro drug release. The optimized formulation was subjected to accelerated stability study for 3 mo. Results: The optimized orally disintegrating tablet formulation exhibited a disintegration time of 2-3 min and complete drug release i.e. more than 85 % drug release within 10 min while performing in vitro drug release study. This is a prerequisite for faster action in the case of patients suffering from Alzheimer’s disease. Accelerated stability studies indicated good physical and chemical stability of the optimized formulation. Conclusion: Developed orally disintegrating tablet formulation of memantine hydrochloride could release the drug faster compared to conventional immediate-release tablets which is useful in paediatric, geriatric and psychiatric patients

DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DELIVERY SYSTEM OF METOCLOPRAMIDE HYDROCHLORIDE

Objective: Metoclopramide hydrochloride (meto) is indicated in the treatment of diabetic gastro paresis. It is also used in the treatment of pregnancy-induced morning sickness. Present work involved the development of a chrono-modulated delivery system of meto, intended to be taken at bedtime which would elicit the therapeutic response early in the morning when needed the most to prevent the symptoms of diabetic gastro paresis and morning sickness. Methods: Immediate release tablets of meto were prepared and optimized for disintegration time and in vitro drug release. Subsequently, these tablets were compression coated using various ratios of glyceryl dibehenate and diluents. The resulting tablets were evaluated for disintegration time and in vitro drug release. Optimized formulation was subjected to accelerated stability studies for 3 mo. Results: The optimized immediate release tablets exhibited disintegration time of 2-3 min and more than 90% drug release within 30 min. These tablets when compression coated with the optimized ratio of glyceryl dibehenate and di-calcium phosphate could delay the disintegration time to 251 min. In vitro release study of the tablets showed the lag phase of 4 h after which there was a complete drug release within 1 h. Accelerated stability studies indicated good physical and chemical stability of the formulation. Conclusion: Chrono-modulated formulation of meto could delay the release of the drug by four h. This lag in the release is expected to modulate the time of therapeutic response of meto early in the morning at 6-7 h interval after the administration of dosage form at bedtime

Strong exciton-localized plasmon coupling in a-Ge24Se76/AuNP heterostructure

L

The Effects of Dual IQOS and Cigarette Smoke Exposure on Airway Epithelial Cells: Implications for Lung Health and Respiratory Disease Pathogenesis

Background Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone. Methods Human airway epithelial cells (BEAS-2B) were exposed to either CS, IQOS or their dual combination (CS+IQOS) at concentrations of 0.1%, 1.0%, 2.5% and 5.0%. Cytotoxicity, oxidative stress, mitochondrial homeostasis, mitophagy and effects on epithelial–mesenchymal transition (EMT) signalling were assessed. Results Both CS and IQOS alone significantly induced loss of cell viability in a concentration-dependent manner which was further enhanced by dual exposure compared with IQOS alone (p\u3c0.01). Dual exposure significantly increased oxidative stress and perturbed mitochondrial homeostasis when compared with CS or IQOS alone (p\u3c0.05). Additionally, dual exposure induced EMT signalling as shown by increased mesenchymal (α-smooth muscle actin and N-cadherin) and decreased epithelial (E-cadherin) markers when compared with CS or IQOS alone (p\u3c0.05). Conclusion Collectively, our study demonstrates that dual CS+IQOS exposure enhances pathogenic signalling mediated by oxidative stress and mitochondrial dysfunction leading to EMT activation, which is an important regulator of small airway fibrosis in obstructive lung diseases

Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, and Epithelial-Mesenchymal Transition by Modulating the SIRT1/Nrf2 Axis

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, i.n) were used to assess cytotoxicity, oxidative stress, epithelial-mesenchymal transition (EMT), Sirtuin1 (SIRT1), inflammation-related cellular signaling, and lung function. PIP treatment protects cells from CSE-induced lung epithelial cell death. PIP treatment restores the epithelial marker (p \u3c 0.05) and decreases the mesenchymal, inflammatory markers (p \u3c 0.05) in both in vitro and in vivo models. The PIP treatment improves the altered lung function (p \u3c 0.05) in mice induced by CS exposure. Mechanistically, PIP treatment modulates SIRT1 thereby reducing the inflammatory markers such as IL-1β, IL-6 and TNF-α (p \u3c 0.05) and enhancing the epigenetic marker HDAC2 (p \u3c 0.05) and antioxidant marker Nrf2 (p \u3c 0.05) expressions. Thus, PIP alleviates pulmonary inflammation by modulating the SIRT1-mediated inflammatory cascade, inhibits EMT, and activates Nrf2 signaling

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe