FORMULATION AND OPTIMIZATION OF FLOATING TABLETS OF CLOPIDOGREL BISULPHATE USING DESIGN OF EXPERIMENTS

Objective: The present study aimed at designing of floating matrix tablet of clopidogrel bisulphate by design of experiments.Methods: The tablets were prepared by direct compression technique using hydroxypropyl methylcellulose K15 (HPMC) as a matrix polymer and sodium bicarbonate as a gas generating agent. In order to optimize the concentration of HPMC (X1) and sodium bicarbonate (X2), a 32 full factorial design was employed. The tablet formulations were evaluated for floating lag time (Y1), floating or buoyancy time (Y2), percent water uptake, and differential scanning calorimetry (DSC) and in vitro drug release (Y3).Results: The formulation variables, HPMC concentration, and sodium bicarbonate concentration exerted a significant effect on floating behavior and drug release characteristics of the tablet. The optimized formulation, with 15% sodium bicarbonate concentration and 30 % HPMC concentration resulted in 5±2.6 sec of floating lag time, 22.0±0.6 h of floating time and 42.0±0.99% of clopidogrel bisulphate release in 8 h of dissolution study. The drug release mechanism was identified as nonfickian. The water uptake studies revealed that with an increase in HPMC concentration, there was an increase in swelling index of tablet whereas higher sodium bicarbonate concentration supported the faster erosion of matrix tablets. DSC study revealed no interaction of drug and polymers. The lower percentage error between predicted and observed responses of the optimized formulation validated the design.Conclusion: The study demonstrated successful designing of floating clopidogrel bisulphate tablet with factorial design

FORMULATION OPTIMIZATION OF PROMETHAZINE THEOCLATE IMMEDIATE RELEASE PELLETS BY USING EXTRUSION-SPHERONIZATION TECHNIQUE

Objective: Promethazine theoclate is a BCS Class II drug having anti-histaminic property and mainly used for the treatment of motion sickness and postoperative emesis. The main objective of the research work was to formulate and optimize immediate release pellets of promethazine theoclate by using the extrusion-spheronization technique to offer immediate release dosage form suitable for treatment of nausea and vomiting associated with motion sickness and post-operative conditions.Methods: Immediate release pellets of promethazine theoclate were prepared by using microcrystalline cellulose (MCC) and corn starch as filler and disintegrant respectively along with other excipients. Pellet formulation was further optimized for bulk density, disintegration time and percent drug release after 10 min. using 32 factorial design. Formulations were also characterized for drug-polymer interactions using Differential Scanning Calorimetry (DSC), surface morphology by Scanning Electron Microscopy (SEM) and other physicochemical properties.Results: Optimised pellet formulation contains 2.5:4.5:1 ratio of MCC: Corn Starch: Drug and spheronization time of 60 seconds showing highest percent yield of 78% and immediate drug release of 100.52±0.65% after 10 min.Conclusion: Promethazine theoclate pellets formulated in this study can serve as an alternative to tablet dosage form which can give immediate drug release for treatment of motion sickness and postoperative emesis

A COMPARATIVE ASSESSMENT OF PHARMACOLOGICALLY ACTIVE PRINCIPLES AND ANTIOXIDANT ACTIVITY OF COMMONLY OCCURRING MUCUNA SPS. IN INDIA

The genus Mucuna (Fabaceae) includes about 150 species and almost all the species are reported to contain L-3,4-dihydroxy phenylalanine (L-Dopa), a non-protein amino acid that acts as precursor for the neurotransmitter dopamine, used in the treatment of Parkinsons disease. The present study was aimed to assess the pharmacologically active principles and antioxidant activities of Mucuna pruriens (L.) DC., Mucuna bracteata DC., Mucuna cochinchinensis (Lour.) A. Chev. black seeds sp. and Mucuna cochinchinensis (Lour.) A. Chev. white seeds sp. The aqueous extract of plant material was subjected to assess the pharmacologically active principles by using L-dopa quantification, determination of protein and flavonoids, total phenolic content, Inhibition of DPPH radical and Reducing power/Ferric reducing antioxidant potential (FRAP) assays. The results obtained showed that, Mucuna cochinchinensis black seeds sp. has highest protein, total phenolic content, L-dopa content and DPPH radical scavenging activity. Mucuna bracteata seeds showed highest flavonoid content whereas, in FRAP assay Mucuna pruriens extract showed highest potential to reduce the ferric ions. It can be concluded from this study that, L-DOPA possesses antioxidant activity which was supported by in-vitro antioxidant assays. This indicates that the antioxidant activity of the aqueous extracts of all the Mucuna sps. may be due to the presence of L-Dopa content in its seed

Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential

Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state. These cells were absent in healthy livers but increasingly prevalent as chronic liver disease progressed. Copy number variation (CNV) analysis of microdissected tissue demonstrated that daHep-enriched regions are riddled with structural variants, suggesting these cells represent a pre-malignant intermediary. Integrated analysis of three recent human snRNA-seq datasets confirmed the presence of a similar phenotype in human chronic liver disease and further supported its enhanced mutational burden. Importantly, we show that high daHep levels precede carcinogenesis and predict a higher risk of hepatocellular carcinoma development. These findings may change the way chronic liver disease patients are staged, surveilled, and risk stratified

Status and Prospects of ZnO-Based Resistive Switching Memory Devices

In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges

SPHERICAL CRYSTALLIZATION A NOVEL APPROACH FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT OF SIMVASTATIN

Simvastatin is commonly used antihyperlipidemic in the treatment of hypercholesterolemia and dyslipidemia. As evidenced form the scientific investigation, it is reported for its lower solubility and poor dissolution rate. The aim of the present investigation was to develop simvastatin spherical agglomerates to improve its solubility and dissolution characteristics by spherical agglomeration method. The crystallization media used was methanol, water and chloroform as bridging liquid and PVP K-30 as a polymer. The process variables such as amount and type of (bridging liquid and polymer), stirring speed and stirring time were optimized and reported. The spherical agglomerates were further subjected for determination of % drug content, particle size analysis, solubility and dissolution rate. The agglomerates were also characterized by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Powder Diffraction (XRD) analysis and affirmed. Among the entire parameters spherical agglomerates obtained with methanol (7ml), water (50ml), chloroform (1.5ml) and PVP K-30 (0.5%) showed improvement in solubility and dissolution rate in comparison with pure drug. The spherical agglomerates showed significant improvement in dissolution from a value of 25.53% for pure simvastatin to 91.31% of spherical agglomerate. The spherical agglomerates of optimized batch were directly compressed and dissolution profile was compared with marketed tablet. Such a technique can successfully be employed to improve solubility and dissolution characteristic of poorly soluble drugs

RAPD-PCR ANALYSIS OF BIXA ORELLANA L. AND SALACIA CHINENS L. TO STUDY GENETIC DIVERSITY

ABSTRACT Bixa orellana L. and Salacia chinensis L. are medicinal plants and native tropical trees of Sri Lanka and Southern region of India which are used in Indian system of medicine to treat various diseases. There is a need to preserve and explore their quantum of genetic variation by analysing the polymorphism between the these plants. Therefore, our aim was to analyse interrelationship and genetic polymorphism between these plants by RAPD Profiling. RAPD is a technique that is based on the amplification of DNA by the use of the polymerase chain reaction (PCR) with short nonspecific primers. RAPD results in amplification of genome regions flanked by the specific priming sites. Our research work suggests that there is much lesser genetic variation between the two species. Both of these plants reproduced four highly monomorphic bands. Thus, study will help in determining genetic variation among Bixa orellana L. and Salacia chinensis L. which are medicinally important and will develop ways to conserve the medicinal aspects of them