IN VITRO IN VIVO CORRELATION OF DEXTROMETHORPHAN HYDROBROMIDE MODIFIED RELEASE TABLETS: AN INTERNAL VALIDATION EVALUATION

ABSTRACTObjectives: The purpose of this study was to develop and validate in vitro and in vivo correlation (IVIVC) for newly developed dextromethorphanhydrobromide sustained-release (SR).Methods: During the development of a once-daily SR tablet of dextromethorphan hydrobromide, an extrapolative in vitro drug release method wasdesigned and statistically evaluated using three formulations with varying release rates. The similarity factor (f2) was used to analyze the dissolutiondata. Three-way crossover study design was conducted in six healthy human subjects under fasting condition.Result: The formulations were evaluated by using area under the plasma concentration-time curve, (AUC0-∞), time to reach peak plasma concentration,Tmax, and peak plasma concentration Cmax, while correlation was determined between in-vitro release and in-vivo absorption. A linear correlationwas observed between the absorption and dissolution profiles of the drug. The prediction error (%) was determined to check how well a given modelcan accurately predict a pharmacokinetic parameter of the drug. The predicted Cmax and AUC found to be −6.98 and −8.55 and for AUC was 7.76 and8.82% respectively.Conclusion: In conclusion, a Level A IVIVC explaining the complete time-course of plasma concentrations was developed and validated, internally fordeveloped dextromethorphan hydrobromide SR formulations.Keywords: Dextromethorphan hydrobromide, Dissolution, Bioavailability, Sustained-release, In vitro and in vivo correlation

Electric Vehicles Charging Stations’ Architectures, Criteria, Power Converters, and Control Strategies in Microgrids

Electric Vehicles (EV) usage is increasing over the last few years due to a rise in fossil fuel prices and the rate of increasing carbon dioxide (CO2) emissions. The EV charging stations are powered by the existing utility power grid systems, increasing the stress on the utility grid and the load demand at the distribution side. The DC grid-based EV charging is more efficient than the AC distribution because of its higher reliability, power conversion efficiency, simple interfacing with renewable energy sources (RESs), and integration of energy storage units (ESU). The RES-generated power storage in local ESU is an alternative solution for managing the utility grid demand. In addition, to maintain the EV charging demand at the microgrid levels, energy management and control strategies must carefully power the EV battery charging unit. Also, charging stations require dedicated converter topologies, control strategies and need to follow the levels and standards. Based on the EV, ESU, and RES accessibility, the different types of microgrids architecture and control strategies are used to ensure the optimum operation at the EV charging point. Based on the above said merits, this review paper presents the different RES-connected architecture and control strategies used in EV charging stations. This study highlights the importance of different charging station architectures with the current power converter topologies proposed in the literature. In addition, the comparison of the microgrid-based charging station architecture with its energy management, control strategies, and charging converter controls are also presented. The different levels and types of the charging station used for EV charging, in addition to controls and connectors used in the charging station, are discussed. The experiment-based energy management strategy is developed for controlling the power flow among the available sources and charging terminals for the effective utilization of generated renewable power. The main motive of the EMS and its control is to maximize usage of RES consumption. This review also provides the challenges and opportunities for EV charging, considering selecting charging stations in the conclusion.publishedVersio

Involvement of Enterobacter cloacae in the mortality of the fish, Mugil cephalus

Enterobacter cloacae, an enteric bacterium that belongs to the family Enterobacteriaceae, is widely distributed in nature. It is found in faeces of humans and animals, water, soil, plants, plant materials, insects and dairy product

SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons

Voltage-gated Kv2.1 potassium channels are important in the brain for determining activity-dependent excitability. Small ubiquitin-like modifier proteins (SUMOs) regulate function through reversible, enzyme-mediated conjugation to target lysine(s). Here, sumoylation of Kv2.1 in hippocampal neurons is shown to regulate firing by shifting the half-maximal activation voltage (V1/2) of channels up to 35 mV. Native SUMO and Kv2.1 are shown to interact within and outside channel clusters at the neuronal surface. Studies of single, heterologously expressed Kv2.1 channels show that only K470 is sumoylated. The channels have four subunits, but no more than two non-adjacent subunits carry SUMO concurrently. SUMO on one site shifts V1/2 by 15 mV, whereas sumoylation of two sites produces a full response. Thus, the SUMO pathway regulates neuronal excitability via Kv2.1 in a direct and graded manner

Matrix metalloproteinases in chemoresistance: regulatory roles, molecular interactions, and potential inhibitors

Cancer is one of the major causes of death worldwide. Its treatments usually fail when the tumor has become malignant and metastasized. Metastasis is a key source of cancer recurrence, which often leads to resistance towards chemotherapeutic agents. Hence, most cancer-related deaths are linked to the occurrence of chemoresistance. Although chemoresistance can emerge through a multitude of mechanisms, chemoresistance and metastasis share a similar pathway, which is an epithelial-to-mesenchymal transition (EMT). Matrix metalloproteinases (MMPs), a class of zinc and calcium-chelated enzymes, are found to be key players in driving cancer migration and metastasis through EMT induction. The aim of this review is to discuss the regulatory roles and associated molecular mechanisms of specific MMPs in regulating chemoresistance, particularly EMT initiation and resistance to apoptosis. A brief presentation on their potential diagnostic and prognostic values was also deciphered. It also aimed to describe existing MMP inhibitors and the potential of utilizing other strategies to inhibit MMPs to reduce chemoresistance, such as upstream inhibition of MMP expressions and MMP-responsive nanomaterials to deliver drugs as well as epigenetic regulations. Hence, manipulation of MMP expression can be a powerful tool to aid in treating patients with chemo-resistant cancers. However, much still needs to be done to bring the solution from bench to bedside

Crystal and Molecular Structure of an Acridinedione

The title compound, 10-(4-hydroxybenzoylamino)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridinedione monohydrate, C_20H_2_2N_2O_4.H_2O, consists of partially hydrogenated acridine moiety with one benzoylamino substituent on the central ring. The compound crystallizes in monoclinic system with P21/c space group and the unit cell constants are: a = 11.142(4), b = 12.266(2), c = 13.320(2) $A^o$; \beta = 91.76(2)° and V = 1819.6(8) $A^3$. The central ring (B) adopts boat and the outer rings (A and C) adopt sofa conformations. The water molecule takes part in OW-H...O and N-H...OW hydrogen bond formation with acridinedione and benzoylamino group. The oxygen atom O1 interacts through O-H...O bond with the hydroxyl group and in a head-to-tail link up of molecules that results in the formation of an infinite supra molecular chain

A Novel mode of Carbohydrate Recognition in Jacalin, Moraceae Plant Lectin with a Beta-Prism Fold

Jacalin, a tetrameric two-chain lectin (66,000 M-r) from jackfruit seeds, is highly specific for the tumour associated T-antigenic disaccharide. The crystal structure of jacalin with methyl-alpha-D-galactose reveals that each subunit has a three-fold symmetric beta-prism fold made up of three four-stranded beta-sheets. The lectin exhibits a novel carbohydrate-binding site involving the N terminus of the alpha-chain which is generated through a post-translational modification involving proteolysis, the first known instance where such a modification has been used to confer carbohydrate specificity. This new lectin fold may be characteristic of the Moraceae plant family. The structure provides an explanation for the relative affinities of the lectin for galactose derivatives and provides insights into the structural basis of its T-antigen specificity

Development and Application of a Validated LiquidChromatography-Mass Spectrometry Method fortheDetermination of Dexchlorpheniramine Maleate in Human Plasma: Determination of dexchlorpheniramine

Aconvenient liquid chromatographic-single Quadrupole mass spectrometric(LC-MS) method was developed and validated for dexchlorpheniramine maleate (INNname: chlorphenamine) determination in human plasma. The need for just a singleliquid-liquid extraction with ethyl acetate and being highly sensitive were theadvantages of this method. The linearity was also excellent over the range of 1 to150 ng.ml-1of dexchlorpheniramine maleate concentration. The method wasstatistically validated for its selectivity, linearity, precision and robustness. This methodwas successfully applied to the analysis of chlorpheniramine maleate in clinicalstudies

Not Available

Not AvailableNot AvailableNot Availabl