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Present pandemic situation due to the appearance of COVID-19 has put the world in a miserable condition More than 2 5 million people have been infected with the causal strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) The first case of COVID-19 infection was reported in China in December 2019 Scientists are searching the effective tool to combat this virus The study has been undertaken by the scientists towards finding effective medicine, vaccine as well as robust techniques to detect this virus Besides development of new treatment, the application of clinical data analytics has also been observed for the off-label use of the already available medications As a part of the real time application of science and technology, several clinical trials has been in process to extract the best answer against COVID-19 In present article, a comprehensive review has been carried out to conscripting the available knowledge about discovery, genomic structure, mechanism of infection and clinical features of SARS-CoV-2 Presently available procedures for detection of this virus have been highlighted Besides these, available treatments which have been explored by the researchers worldwide, includes precisely convalescent plasma therapy, monoclonal antibody therapy as well as antiviral medications along with their regulatory status, have been discussed elaborately which will definitely enrich the global understanding as well as proficient ability to combat this pathogens © 2020 Chemical Publishing Co All rights reserved

Among the secondary metabolites which are widely distributed in plants and foods in plant origin flavonoids is important one. Flavonoids have antioxidant activities as free radical scavenging action. They also have anti-inflammatory, antiulcer and anti-carcinogenic activities. Diosmin and hesperidin, the metabolites of which are diosmetin and hesperitin respectively are considered in the present study. Diosmetin has anticancer, antioxidant and blood lipid lowering activities. It also enhances venous tone and microcirculation and by reducing systemic oxidative stress it protects capillaries. Hesperitin also has antioxidant, anti-inflammatory, blood lipid and cholesterol lowering, anti-carcinogenic activities. In the present study efforts were given to develop and validate a bioanalytical method for simultaneous estimation of diosmetin and hesperitin in human plasma by liquid chromatography electron spray ionization mass spectrometry with an application to the analysis of plasma samples obtained from the comparative pharmacokinetic studies on healthy human volunteers under the framework of bioequivalence study. The developed method for simultaneous determination and quantification of diosmetin and hesperitin in human plasma was validated as per the US-FDA guidelines. The validation parameters found within the specified regulatory limit, hence acceptable. The present method also has a short run time (6.0 min) and easy extraction process. The developed method was found to be simple, specific, highly selective, sensitive and reproducible. This was applied for the analysis of the volunteer plasma samples. On the basis of comparison of the AUC0-t, the relative bioavailability of the test preparation was found 100.94 and 95.09% for diosmetin and hesperitin respectively of that of the reference preparation.

A simple and highly sensitive bioanalytical method was developed and validated for simultaneous quantification of nimesulide (NSD) and its active metabolite 4-hydroxy-nimesulide (M1) in human plasma by liquid chromatography-tandem mass spectrometer (LC-MS/MS) and applied in a bioequivalence study performed on Indian subjects. The bioanalytical method was carried out by LC-MS/MS with celecoxib (CXB) as an internal standard (IS) using liquid–liquid extraction technique. The chromatographic separation was performed on a reversed-phase Agilent eclipse plus C18 (75 mm × 4.6 mm, particle size 3.5 µm) column with a mobile phase of acetronitrile and water containing 5 mM ammonium formate (9:1, v/v). Method validation and clinical sample were analysed as per USFDA and EMA guidelines and results met the acceptance criteria. The lower limit of quantitation of NSD and M1 was found 10 ng/mL with a large linearity range from 10 to 6000 ng/mL for both NSD and M1 using only 100 µL of plasma and reported no matrix effect. The multiple reaction monitoring transitions of m/z 307.20 → 229.20, m/z 323.00 → 245.00 and m/z 380.20 → 316.20 were used to measure NSD, M1 and CXB (IS), respectively. The assay method was successfully applied for the simultaneous quantification of both NSD and M1 in plasma samples after oral administration of nimesulide 100 mg tablet in healthy human subjects.

Plasmodium is the malaria parasite that completes the life cycle between two different hosts, such as human and Anopheles mosquito. These parasites go through several developmental stages like exo-erythrocytic stage that is absent in Plasmodium falciparum, so relapses do not occur. The drugs which contain three P’s like proguanil, primaquine, and pyrimethamine kill schizonts in the liver. Due to prolonged treatment of high dose of chloroquine, there may be serious side effects named as Bull’s eye maculopathy. Atovaquone is rapidly acting blood schizonticide that acts by collapsing the parasite’s membrane. Artemisinins are the fastest acting drugs against malaria. Mepacrine is an anti malarial drug which concentrates in collagen tissue. Infection by P. falciparum is the most lethal form of malaria, in this case agglutination of the infected RBC occurs and these agglutinised RBCs block the capillary vessels of the internal organs. Tafenoquine is a single dose medication for radical cure of P. vivax malaria. People with an enzyme problem G6PD deficiency can cause severe anaemia. At least two genes affecting red cells which are resistant to P. falciparum are autosomal gene for haemoglobin S (HbS) and the gene linked to sex G6PD variant gene. Anaemia is the main result due to malaria by haemolysis of infected and uninfected erythrocytes, dyserythropoiesis, splenomegaly and depletion of folate stores. Cerebral malaria is the most urgent complication that is manifested by confusion or coma by clusters of parasitized red blood cells to form large size cells of the capillary circulation which adhere to the vascular endothelium and block the circulation causing cerebral hypoxia and resulting to neurological symptoms and diagnosed cerebral malaria. Blackwater fever associated with falciparum malaria is mostly common with individuals that have taken antimalarial treatment irregularly or deficient in G6PD deficiency. Tropical splenomegaly is another symptom in falciparum malaria. HbAS was the genetic variant which associated with protection against malaria incidence and other variants such as alpha thalassemia, G6PD deficiency, polymormhism of genes encoding NOS2A and TNF, as well as protection against uncomplicated malaria. Key words: Malaria, pathogenicity of malaria, parasite of malaria.

The aim of this present study was to develop and formulate sustained release coated metoprolol tartrate matrix granules and to design an in-vitro in-vivo correlation (IVIVC) tool based on bioavailability data available from human volunteers. USP apparatus II, paddle type was used for generation of in-vitro drug release data for each formulation. The similarity factor (f2) was determined using dissolution data parameters of the formulations. Twenty-four healthy male volunteers participated in the two-way crossover bioequivalent study where the volunteers were treated in a completely randomized fashion. The percent drug dissolved in the dissolution test and percent absorbed data shows a ‘level A’ IVIVC was achieved with a good linear regression relation. Different release rate formulation including Fast, Moderate and Slow release formulations exhibited an excellent covenant between the three dosage forms. Key words: Sustained-release capsules, metoprolol tartrate, bioavailability, in-vitro in-vivo correlation (IVIVC), humans.

The experimental study mainly focused on evaluation of sub-chronic oral toxicity of sustained formulation of metoprolol succinate. After the formulation development of multiparticulate sustained release capsules, there was an urgent need to analyze their in vivo bioavailability in healthy normal human volunteers. Prior to use in human population, a subchronic oral toxicity study was performed on Swiss Albino rats, of the final formulated product to assess the possible therapeutic outcome and related toxicity. The final objective of the study is to find out the pharmacological interaction between the drugs and the excipients that may lead to toxicity to human volunteers. The sustained release formulation of Metoprolol tartrateat was administered in different dose according to the 28 days of study dosing schedule in 48 albino Wistar rats of either sex (24 males and 24 females); periodical safety and efficacy observation were done followed by blood chemistry, hematology and histopathological examination at the end of the study. All the animals were found alive after the study period. No behavioral abnormalities were found in the study animals. Statistical analysis of the results including various parameters like body weight, blood chemistry, hematology and histopathological evaluation did not produce any major differences between control and treated groups. The reformulated sustained release hydroxy propyl methyl cellulose based granules of metoprolol tartrate did not cause any subchronic toxicity to the study animals under experimental conditions. Key words: Preclinical sub-chronic toxicity study, rats, formulation, metoprolol tartrate.

The current investigation deals with an validated Liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) analytical method for the quantification of micronised domperidone in plasma of human volunteers. The validation of LC-MS/MS method was accomplished by evaluating the inter-day and intra-day precision and accuracy in a linear concentration range of 3.33-100 ng/ml. The entire study was an attempt to evaluate the comparison index of the bioavailability study of micronised domperidone tablet formulation with that of conventional domperidone tablet containing 20 mg of domperidone. Both the formulations were given orally as a single dose cross over design. The washout period was taken as 1 week. A single-dose, two-sequence, two-treatment, two-period crossover Bioequivalence study of two formulation were performed on 12 Indian healthy male volunteer. The estimation of domperidone concentration in human plasma was determined by the validated LC-MS/MS method. The various pharmacokinetics parameters like peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax), area under the plasma concentration-time curve (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC0-∞), of both the formulations were evaluated and compared. The results evaluated by estimated pharmacokinetic parameters did not find any statistically significant difference between the two formulations. The relative bioavailability of micronized test formulation was found to be 104.62% to that of reference conventional formulation. Key words: Bioequivalence, domperidone, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis, pharmacokinetics.

A vast proportion of synthesis based polymers used to develop matrix drug delivery systems are too some extent harmful to patients who are taking those formulations for shorter and longer duration ...

Supplemental Material for LC-MS/MS determination of 4-hydroxynimesulide, an active metabolite of nimesulide and application to bioequivalence study in Indian subjects by Dhiman Halder, Shubhasis Dan, Pradipta Sarkar, Dibya Das, Umesh Chandra Halder and Tapan Kumar Pal in European Journal of Mass Spectrometry

A sensitive, specific and reproducible liquid chromatography coupled to tandem mass spectrometric method was developed and validated for the estimation of ciprofloxacin, an extensively used second-generation quinolone antibiotics, in human plasma. A liquid-liquid extraction of ciprofloxacin and the internal standard, ofloxacin, has been approached from the biological matrix using chloroform. Chromatographic separation was achieved in positive ion modes, isocratically on a 3.5 μm C18 analytical column (75 mm×4.6 mm, i.d.) with 0.2% formic acid solution in water: methanol (10:90, v/v) as mobile phase, at a flow rate of 0.5 mL.min−1. The MS/MS ion transitions were monitored as 332.0→231.3 for ciprofloxacin and 362.2→261.0 for IS. The method showed good linearity in the range of 0.01–5.00 μg.mL−1 (r 2 >0.99) with a good precision (3.37–12.60%) and accuracy (87.25–114%). At the same time, ciprofloxacin was found to be stable during stability studies viz. bench-top, auto-sampler, freeze-thaw cycle and long-term. The developed and validated method was successfully applied to measure plasma ciprofloxacin concentrations in a single dose bioequivalence study.

Rheumatoid arthritis is a chronic inflammatory disease condition in synovial joints causing progressive destruction of synovial fluid resulting moderate to severe pain. Oxidative stress plays a major role in inflammation. Free radicals which are found to have in our body, either as a product of metabolism or incorporated from our environment, plays a major role in formation of oxidative stress, that leads to inflammation. To reduce this oxidative stress anti-oxidant may contribute in management of inflammation. In this study, the antioxidant and anti-inflammatory property of tartaric acid and β- carotene has established and compared with vitamin C and diclofenac sodium as standard drug. The free radical scavenging assay and protein denaturation assay was conducted for this purpose. The % inhibition confirmed the activity of individual molecules. According to the study outcome, Tartaric Acid is more effective antioxidant and anti-inflammatory agent than β-carotene. And so far it can be used as anti-rheumatoid arthritic agent. The IC50 values and graphical representations confirm the result.

Herbal medicines have recently been used for treatment of various diseases. The unwanted reaction and other concern like authenticity of herbal drugs is one of the important issues that have been addressed in this article. Toxicity of various important herbal drugs which are used regularly may also induce fatal reaction in our body. Herbal drug interaction with conventional drug and their serious consequences may be also life threatening for the patients who consume herbal drugs. Drug mutagenicity and contamination of herbal drugs are discussed here with suitable example. Drug authenticity with suitable illustration is also depicted in this review article. The aim of this article is to deliver an insight to the critical points of modern herbal drugs therapy and to find the scope for future scientists to overcome the serious issues regarding the herbal drugs treatment in recent era.

This present experiment deals with a formulation of novel drug delivery system of chitosan implants to modulate the release of ketorolac through the fabrication of subcutaneous implant. The implants were prepared by compression technique. The chemical stability and the characteristic features of surface morphology of the implants were confirmed by using FTIR and SEM. The thermodynamic behavior of the novel implants was investigated by using DSC/TGA. The loading capacity of Ketorolac into chitosan implants was also evaluated. The release kinetic parameters were studied in dissolution media of phosphate buffer solution (PBS). The results find that the final formulation maintains chemical stability of the drug. The morphological features of the implant confirmed uniform inclusion and distribution of ketorolac into the chitosan matrix with an evidence of porous structure. The drug release pattern of the Ketorolac exhibited controlled release behavior from chitosan implants up to 45 d governed mainly by drug diffusion mechanism. The formulated of novel implants have shown a great potential in the long term subcutaneous delivery of ketorolac.

The review article explores the various problems associated with hydrolysis which occurs during formulation and the various solutions of it. The moisture content either the drug or the excipients affect the formulation, by hydrolysis, thus it is important to find out ways to prevent it and thus protect the formulation and provide a greater stability under processing and storage condition. The common moisture interactions which occur are water-solid interactions, water-amorphous solid interactions, drug-excipient interactions and the change in the crystal habit of the solids. The science behind the hydrolysis is due to the moisture sensitive functional group of the ingredient, and the other freely moveable living groups. Amides, lactams, esters, lactones, chloride are the functional groups most susceptible to hydrolysis. The hydrolysis of excipients, including both polymeric and non-polymeric also show great impact on the stability of the drugs. The excipients used in the form of sweeteners, plasticizers, solvents, surfactants, wetting agents, emollients, antioxidants, lubricants, preservatives, and etc. have effects on the drug stability. As a result, several solutions are found to prevent unwanted hydrolysis in different dosage forms. The main parameters which are likely to solve this issue are pH, buffers, surfactants, non-aqueous solutions, suspensions, lyophilization, packaging and an adequate proportion of the desiccant use.

A simple, rapid and sensitive high-performance liquid chromatography–tandem mass spectrometry method has been developed and validated according to the Food and Drug Administration (FDA) guidelines for simultaneous determination of metoprolol and telmisartan in rat plasma using atorvastatin as an internal standard. The analytes were separated on a Gemini C18 column (50 mm × 4.6 mm, 5 µm) with an isocratic mobile phase of methanol–water containing 0.5 % formic acid (9:1, v/v) at a flow rate of 0.5 mL/min. The estimation was carried out by triple quadrupole mass spectrometry using electrospray ionization technique, operating in multiple reaction monitoring and positive ion modes. Simple liquid–liquid extraction was used for sample preparation. Linearity was achieved over the concentration range of 1–500 ng/mL for both the analytes in rat plasma. Results of validation parameters of the method were with the acceptance criteria of the FDA guidelines. The method was found suitable to quantitatively assess the pharmacokinetics of metoprolol and telmisartan in rat following administration of a single oral dose 2.5 and 2 mg/kg body weight, respectively in Wistar albino rat.

Letrozole (CAS Number-112809-51-5) is widely used as an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery. For quantitation of letrozole, negative polarity was used to achieve adequate response because this was highly sensitive for compounds with high electron affinity. It was applied to fragment the analytes and to obtain intense and consistent product ions. The deprotonated precursor ions [M-H]−at m/z 284.1 was observed in Q1(MS) for letrozole. Characteristic product ions found in Q3(MS) was at m/z 242.0, 102.1, 126.7, 140.7, 215.1, 240.3 for letrozole. Most stable and consistent fragment ion selected m/z 242.0 having the triazole ring. For the internal standard (tolbutamide) the fragment at Q1 and Q3 having m/z 269.1 and 170.1 was responsible for possessing the methoxyethyl-phenoxy group. In the present study LC-MS/MS-ESI method was attempted to develop for detection and quantification of letrozole in human plasma. Therefore, it can be concluded from the present study findings that developed method by using LC-MS/MS API 2000 and liquid-liquid extraction technique for letrozole in human plasma was found to be simple, specific, sensitive, reproducible and fully validated in according to EMA guidelines. The present method was found superior enough to be applied to comparative pharmacokinetic studies in future.

Background: Proton Pump Inhibitors (PPI) are observed to be great healer in gastroesophageal reflux disorder (GERD) and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t ), Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵), Peak plasma concentration (C max ), and time to reach peak plasma concentration (t max ). Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence interval for the ratio of the logarithmic transformed AUC 0-t , AUC 0-͵ and C max were 2 within the bioequivalence limit of 80-125% and the relative bioavailability of test formulation was 102.81% to that of reference formulation. The results of this study in healthy human volunteers of 27.92 ± 5.12 yrs (average age), 171.28 ± 6.85 cm (average height) and 66.43 ± 5.21 kg (average weight) support the use of the 10 mg dose tablet newly formulated.

A simple, reproducible, and feasible RP-HPLC method has been developed for simultaneous determination of two commonly used drugs, paracetamol (PCM) and etodolac (EDL), in human plasma. In this specific and accurate method, tinidazole was used as an internal standard. Chromatographic separation was achieved on a Hiber C18 250 × 4.6 mm id, 5 μm particle size, column using the isocratic mobile phase 10 mM potassium phosphate buffer (adjusted to pH 7.5)–acetonitrile (70 : 30, v/v) at a flow rate of 1 mL/min. Detection was at 235 nm. The linear concentration range of the assay was 0.100 to 50.00 μg/mL for both analytes, and the linear regression correlation coefficient was (r2 > 0.99). The recovery of PCM and EDL were 94.03 and 88.27%, respectively. The method was validated for specificity, linearity, precision, accuracy, reproducibility, and stability. The intraday and interday precision and accuracy values for PCM and EDL met the acceptance criteria of U.S. Food and Drug Administration guidelines. PCM and EDL were stable in a battery of stability studies, viz., bench top, dry extract, and freeze-thaw cycles. This developed and validated method was successfully applied to quantitatively assess the PCM and EDL for the first time in human plasma obtained from a pharmacokinetic study performed with 12 healthy human volunteers.

Background: Enalapril (EPL) is an angiotensin-converting enzyme inhibitor for the treatment of hypertension and chronic heart failure. Enalaprilat (EPLT) is an active metabolite that contributes to the overall activity of EPL. Aim: To quantitate EPL along with its metabolite EPLT using LC–MS/MS, a bioanalytical method was developed and validated with tolbutamide in human plasma using a protein precipitation technique. Results: The sensitive and selective method has an LLOQ of 1 ng/ml with a linearity range of 1–500 ng/ml for both EPL and EPLT using 300 µl of plasma without any matrix effect. Conclusion: Linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples after oral administration of 20 mg of EPL maleate in healthy volunteers demonstrate applicability to bioavailability/bioequivalence studies., Lay abstract: The present study describes a sensitive, selective, simple, accurate and reproducible LC–MS/MS method for the simultaneous determination of both enalapril (EPL) and enalaprilat (EPLT) in human plasma. The results obtained indicate the high sensitivity of the described method for analysis of EPL and EPLT, which render this method particularly useful for pharmacokinetic or bioequivalence studies. The proposed method has been applied for the analysis of EPL and EPLT in the plasma of healthy volunteers in a single-dose pharmacokinetic study.

Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure.This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets.Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug.A fast in situ calcium acetate dissolution in pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate fragments and drug dissolution retardation at pH 1.2, which were not found in other pellet types. The preclinical drug absorption rate was lower with calcium acetate loaded than calcium-free alginate pellets. In human subjects, however, the extent and the rate of drug absorption were higher from calcium acetate-loaded pellets than calcium-free alginate pellets. The fine, dispersible and weakly gastric mucoadhesive calcium alginate pellets underwent fast human gastrointestinal transit. They released the drug at a greater rate than calcium-free pellets in the intestine, thereby promoting drug bioavailability.Calcium acetate was required as a disintegrant more than as a crosslinking agent clinically to promote pellet fragmentation, fast gastrointestinal transit and drug release in intestinal medium, and intestinal-specific drug bioavailability.

Supervision provides a foundation for future workers to learn practical skills from a qualified professional, and is essential for the development of a profession. Supervision is also very much essential for developing workforces. Recently CDSCO has proposed to create an IT enabled system for online submission of various information on clinical trialsto streamline the process of approval, maintaining comprehensive database and monitoring The clinical trials for ensuring the protection of rights, safety and well beings of trial subjects and authenticity of the data generated. Looking at the current regulatory environment of clinical trial in India, it is very much important to collate all the information related to four major domains of clinical trial to bioequivalence study captured online in an organized manner. These domains are: Sponsor/ CRO, Investigator, Ethics Committee (EC) and Patient/ volunteer. In order to get access to all the information, all the sponsors/CROs, Investigators and Ethics Committees are required to put the information in a common repository related to a particular CT which will be updated by the stakeholders on day to day basis. The efforts of the Indian Regulators towards ensuring the patient safety and data credibility are discussed in the present study.