bluuebunny/crossref_metadata_2025 huggingface dataset:
Related Impurities High-performance Liquid Chromatography Method Development and Validation for drug combinations: Olmesartan Medoxomil, Chlorthalidone and Cilnidipine
Authors: Shah Pranavkumar , Dhadhuk Bhavin
Published: July 2021

The liquid chromatography mass spectrometry (LC-MS) compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time related impurities reversed phase high-performance liquid chromatography (RP-HPLC) related impurities method has been developed for olmesartan medoxomil (OLM), chlorthalidone (CHLR), and cilnidipine (CIL) drug combinations, and the method has been validated according to ICH and US-FDA guidelines. The chromatographic separation was performed by using Hypersil-BDS Thermo-Scientific, C18 (12.5 cm, 4.6 mm, 5 microns particle size) column. Mobile phase-A was prepared by mixing 3.85 gm ammonium acetate in HPLC water and adjust pH 5.0 by using diluted acetic acid. Acetonitrile was taken as mobile phase-B. Initial mobile phase ratio (55:45 v/v) was adjusted for mobile phase-A: mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for CHLR impurity A, olmesartan (OL), OLM impurity A, were found about 2.7, 3.3, and 7.2 minutes respectively, with a total run time of 18.0 minutes. The linearity calibration plot was performed and found linear relationship over the concentration range of 1.25 limit of quantitation (LoQ)–18.75 μg/mL, 3.6 LoQ–60.0 μg/mL, 3.6 LoQ–60.0 μg/mL respectively for CHLR impurity A, OL and OLM impurity A respectively. The limit of detection (LoD) and LoQ were found 0.4 ppm (μg/mL) and 1.2 ppm (μg/mL), 1.2 ppm (μg/mL) and 3.5 ppm (μg/mL), 1.1 ppm (μg/mL) and 3.3 ppm (μg/mL) for CHLR impurity A, OL and OLM impurity A respectively. The accuracy was determined by recovery studies and was found between 90.0–110.0%. The developed analytical method has been validated for LoD-LoQ, specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to check the quality of OLM, CHLR, and CIL drug combinations.
SYNTHESIS CHARACTERIZATION AND ANTIMICROBIAL ACTIVITIES STUDIES OF N-{2-(4-CHLOROPHENYL) ACETYL} AMINO ALCOHOLS DERIVED FROM α-AMINO ACIDS
Authors: Venkateshappa G. , Shivaraju G. , Raghavendra Kumar P.
Published: July 2021

Amino acids play important roles in organisms to sustain in living state and perform as body constituents, enzymes and antibodies. At insalubrious situations, use of amino acids derivatives as drugs in the maintenance of normal health is better choice than common unnatural synthetic drugs. This is due to the fact that the amino acids derivatives may be more bio-compatible, biodegradable and eliminate easily than others.  In this sense we have made an effort and report herein the synthesis of N-{2-(4-chlorophenyl) acetyl} amino alcohols synthesised by reduction of N-{2-(4-chlorophenyl)acetyl} derivatives of (S)-amino acids such as (S)-phenylalanine, (S)-alanine, (S)-methionine, (S)-leucine, (S)-tryptophan and (S)-proline. These newly synthesized amino acids derivatives were analysed by proton, carbon-13 NMR and FT-IR spectroscopy. The composition of solid derivatives was determined by elemental analysis. Further, antimicrobial activities of these derivatives were assessed on usual bacteria K. aerogenes, E. coli, S. aureus and P. desmolyticum and fungi A. flavus and C. albicans. The compounds were witnessed moderate activity than authorised antibacterial and fungal agents Ciprofloxacin and Fluconazole respectively. The antimicrobial studies also revealed that, these derivatives could be better antifungal agents than antibacterial agents. Finally we compared the experimental results of antimicrobial activities with docking studies.
SYNTHESIS, SPECTRAL CHARACTERIZATION AND BIOPOTENTIAL SIGNIFICANCE OF Co(II) AND Ni(II) COMPLEXES WITH BIOLOGICALLY ACTIVE LIGANDS
Authors: Marlin Risana M. , Balasubramaniyan S. , Govindharaju R. , Mukil Meenakshi V. , Jayalakshmi B. , Ramachandramoorthy T.
Published: July 2021

New Cobalt(II) and Nickel(II) metal complexes of 2-aminothiazole (ATZ) and benzoate ion (BEN) ligands were  synthesized under microwave irradiation. The empirical formulae and the structure of the complexes have been deduced from CHN analysis, electrical conductance, magnetic moment, electronic (DRS method), Infra Red spectra, TGA analysis, cyclic voltammetry and powder-XRD techniques. The low electrical conductance values indicate that the complexes are non-electrolyte (1:0) type. The electronic spectra and the magnetic moment indicate the structures of the complexes are found to be octahedral geometry. Infra Red spectra illustrate that 2-aminothiazole and benzoate ion is bonded to the metal ion in a monodentate approach. The antifungal activities of ligands and their cobalt(II) and nickel(II) metal complexes were studied aligned with the few microorganisms by agar - well diffusion method at 100,200 and 400 conc. µg/ml concentration.  The prepared cobalt(II) and nickel(II) metal complexes show prospective action against the tested fungi as compared to free 2-aminothiazole ligand. The free radical scavenging action of the prepared complexes and the ligand has been resolute by measuring their interface with the stable free radical DPPH. The complexes have larger antioxidant activity as compared to the free ligand. DNA-binding properties have been calculated by fluorescence-emissions method. The obtained results suggest that the complexes powerfully bind to DNA because of metal complexes are well-known to speed up the drug action and the capability of healing agent which can repeatedly be enhanced leading coordination with a metal ion.
DEVELOPMENT OF MICROEMULSION FORMULATION FOR ORAL DELIVERY OF ROSUVASTATIN CALCIUM
Authors: Paliwal Himanshu , Solanki Ram Singh , Chauhan Chetan Singh
Published: July 2021

The purpose of conducting this study was to prepare an oral microemulsion formulation of Rosuvastatin calcium (RC) to improve its water solubility. Oil in water microemulsion was formulated using Oleic acid, Tween 80 and Polyethylene Glycol-400(PEG-400) as oil, surfactant and co-surfactant, respectively. The ideal proportion of surfactant: co-surfactant (Smix) was chosen by constructing pseudoternary diagrams. The microemulsion formulations which proved to be stable after thermodynamic stability testing were further evaluated for physical characteristics. Selected formulations were evaluated for droplet size, zeta potential, polydispersity index, viscosity and % drug content. The results were suggestive that optimized microemulsion formulation (F2) was thermodynamically stable and clear having a droplet size of 74.29 nm and zeta potential of -18.44.  In vitro dissolution study for optimized microemulsion was performed using a dialysis bag method and cumulative % drug release was determined. The result from the release study was indicative of improved solubility of Rosuvastatin calcium which may serve to boost up the oral bioavailability of drug.
In silico Screening of Zinc Database for Discovery of Novel Urease Inhibitors as a Remedy to Gastro-Duodenal Ulcer Caused by Helicobacter pylori
Authors: Chopdar K. S. , Mohapatra P. K. , Nayak B. , Raval M. K.
Published: July 2021

Design and synthesis of novel urease inhibitors taking center stage now days with specific attention as a remedy to Helicobacter pylori infection. A number of inhibitors fail in vivo and in clinical trial owing to the toxicity and hydrolytic profile. In the present study, we are making an attempt to screen a large small molecule database, ZINC, for a potential urease inhibitor. The structure based drug discovery approach has been adopted with acceptable ADMET parameters so that the lead molecules may have fair chances of passing in vitro and in vivo trails. The lead molecule in our study, with ID ZINC90446454 is a urea derivative and predicted to be nontoxic. It comes out to be a promising drug candidate with pKd value 7.83, LE 0.429 and LD50 value 10100 mg/kg body weight. Its sulfanyl derivative, with predicted high LD50 (10100 mg/kg body weight), exhibits the feasibility of a disulfide covalent bond with Cys321 in the active site. The derivative may serve as a novel covalent inhibitor with high specificity, high potency and low toxicity. The derivative, in future, may be a successful drug candidate for H. pylori induced gastro-duodenal ulcer.
SYNTHESIS AND BIOLOGICAL EVALUATION OF THIOSEMICARBAZONE ANALOGUES OF ORNIDAZOLE AS ANTIFUNGAL AGENTS
Authors: Kumar N. , Aggarwal T. , Singh G. , Kumar P. , Kumar R. , Kaur C.
Published: July 2021

To synthesize a series of ornidazole thiosemicarbazone analogues on the basis of literature reviews of 2-Methyl-5-nitroimidazoles and thiosemicarbazones and to evaluate all the analogues in vitro for their activity against Aspergillus niger and fumigatus. Thiosemicarbazone analogues were synthesized from oxidising ornidazole with potassium dichromate and refluxing the oxidised product with substituted thiosemicarbazide using ethanol as solvent in the acidic medium overnight. All the synthesized analogues of ornidazole showed good antifungal action against fumigatus and niger except compound C-4. Unsubstituted amine analogue C-2 has shown highest percentage inhibition (96.6%, 500 μg/ml) against fumigatus while aromatic amine with or without electronegative atom analogues C-3 and C-5 has shown highest activity against Aspergillus niger which is two times than standard drug ornidazole (100%, 1000 μg/ml).
Development of Water Transplant Based Single Core Osmotic Pump for Fluvoxamine Maleate Employing Quality by Design Principles
Authors: Umaretiya G. M. , Chavda J. R. , Patel J. K.
Published: July 2021

The present study draw a bead on preparing single core osmotic pump with improved water transplant by employing Quality by Design (QbD) principles to achieve zero order drug release for prolonged period of time. QbD principles were employed in preparing single core osmotic pump by deriving quality target product profile (QTPP), critical quality attributes (CQA) followed by risk assessment using ishikawa diagram and risk estimation matrix. Box-Behnken Design was employed to study the effect of various independent parameters like concentration of Natrosol 250 HX (X1) and concentration of Xylitab (X2) no. of orifice (X3), on various dependent parameters like lag time (Y1) and time required for release 25%, 50%, 75% and 100% drug (Y2, Y3, Y4 and Y5). A controlled space was designed where each criteria or CQA was satisfied. Optimized formulation was further characterized for its efficiency. The results of design suggest the suitability of design for optimization of single core osmotic pump. In the initial period, drug release was driven by no. of orifice which on later stage depends on concentration of swellable polymer and concentration of osmogen. Optimized design was validated by preparing check point batch having less than 5% predicted error. Model fitting with drug release kinetics showed that optimized single core osmotic pump released drug in zero order. Stability data suggested that prepared formulation was stable for 3 month period without significant changes in the CQA. Single core osmotic pump using water transplant was successfully developed for a poorly soluble drug using QbD principles.
STABILITY INDICATING HPTLC METHOD FOR SOFOSBUVIR AND VELPATASVIR IN COMBINATION
Authors: DAMLE MRINALINI C. , Kalaskar Pooja B.
Published: July 2021

The discovery of new direct-acting antiviral drugs gave rise to a leap forward in the treatment of hepatitis C viral infections. For the first time since 1998, the Food and Drug Administration (FDA) approved interferon-free oral treatment paradigms. Among the new treatment regimens, the combinations of Sofosbuvir and Velpatasvir became ideal treatment regimens for being potent, highly tolerated and used once daily. Hence an accurate, precise, selective and sensitive stability indicating method for simultaneous estimation of Sofosbuvir and Velpatasvir by High-Performance Thin Layer Chromatography has been developed and validated. Chromatographic separation was achieved on TLC plates coated with silica gel 60 F254 as stationary phase. Ethyl acetate: iso-propyl alcohol (9:1 v/v) was used as mobile phase.Densitometric scanning was carried out at 260 and 302 nm for Sofosbuvir and Velpatasvir, respectively. The method was successfully validated as per the ICH Guideline. The linear concentration range was100- 2000 ng/band (r2= 0.991) and 100-500 ng/band (r2 = 0.991) for SOF (Sofosbuvir) and VEL (Velpatasvir) respectively. The LOD were 25.16 ng/band and 9.96 ng/band for SOF and VEL, LOQ were 76.25 ng/band and 30.19 ng/band for SOF and VEL.The method could be applied to the quality control and routine analysis of Sofosbuvir and Velpatasvir in their pure forms and pharmaceutical formulations.
EVALUATION OF ANTIHYPERLIPIDEMIC ACTIVITY OF ETHANOLIC EXTRACT OF CROSSANDRA INFUNDIBULIFORMIS LEAVES AND STEMS ON HIGH FAT DIET INDUCED HYPERLIPIDEMIA
Authors: Vasantha Galanki , Venkatesham Allenki , Dayakar Chitturi H.
Published: July 2021

Hypercholesterolaemia is  the state been depicted by an expanded   greasy  substances  called  lipids,  rise in  plasma TCs and TGs levels  it is additionally called hyper lipoproteinemia. The present study was designed to investigate the hypolipidemic effect of ethanolic extract of Crossandra infundibuliformis leaves and stem (ECILS) in high fat diet (cholesterol 2%, sodium cholate 1%, sucrose 48%, peanut oil, methionine 4%, and 47% normal laboratory feed) . The rats feed with High-fat diet containing (cholesterol 2%, sodium cholate 1%, sucrose 48%, peanut oil, methionine 4%, and 47% normal standard laboratory feed) for 1 month, and then they are checked for the blood parameter levels like TC, TGs, LDL, VLDL, and HDL. Ethanolic extracts at low dose (100 mg/kg), significantly reduced the levels of TC, TGL, LDL, VLDL & increased the levels of HDL and reduced the body weights on 30st day, and at medium, high doses it reduced the levels of TC, TGL, LDL, VLDL & increased the levels of HDL and reduced the body weights.
Venlafaxine Hydrochloride Controlled Release Bilayer Tablets: Optimization of Formulation Variable by Using Dyspnea on Exertion
Authors: Dalvadi Hitesh P. , Patel Pritesh J. , Vashi Nirmal , Paul Arindam
Published: July 2021

The current research work was to develop bilayer tablet of venlafaxine hydrochloride to increase drug efficacy for efficient treatment of depression. The satisfactory result of treatment can be achieved upon the maintenance of drug concentration within an effective level in the body, so a uniform and constant drug supply are desirable. An immediate layer of venlafaxine HCl was formulated using super disintegrants, i.e., croscarmellose sodium (CCS) and sodium starch glycolate (SSG); tablet compact by direct compression. HPMC K100M and ethylcellulose (EC) were utilized as release retarding polymers in sustained release layer by wet granulation technique with the help of PVP K30 in IPA solution (10%) as a granulating agent. Full 32 factorial designs were used to find out the optimum quantity of release retardant polymers. Bilayer tablet was evaluated for various parameters, i.e. hardness, friability, weight variation, % drug content, disintegration time (IR layer), and % drug release study. Statically, an analysis was carried out using factor X1 (HPMC K100M) and X2 (EC) for dependent variable % drug release at 8, 12, and 20 hours. A formulation was optimized and a formulation containing 305.36 mg of HPMC K100M and 54.03 mg of ethyl cellulose. Optimized formulation show 47.12 ± 2.1, 59.89 ± 2.2, and 89.06 ± 2.3 drug release at 8, 12, and 20 hours, respectively, which is almost similar to theoretical dose calculation with similarity factor f2 97, 99, and 98%, respectively. Bilayer tablet formulation was observed to be stable and fulfilled all compendia specifications.
Analytical QbD Approach for Development and Validation of RP-High Performance Liquid Chromatography Method for Determination of Tofisopam in Pure Form and Tablets
Authors: Kokane Megha , Pananchery Jeeja , Jadhav Monika , Jain Ashish
Published: July 2021

A novel, simple, optimized reversed-phase chromatography method for assay of Tofisopam in pure and tablet form is developed. The experimental trial was by Box Behnken design using the Design Expert® software 10 version. The attributes selected were peak symmetry, number of theoretical, and peak purity. The predicted data satisfied with actual experimental data. The optimized chromatographic conditions required a quaternary pump with a mobile phase of Water: Acetonitrile 25:75 v/v at 1 mL/min, oven temperature at 25oC at 310 nm using C18(250 × 4.6 mm Id, 5μm) column and PDA detector with a run time of 5 min. The method was validated for linearity, precision, accuracy, and specificity. The method produced a linear response over a concentration range of 4–24 ppm with an overall average accuracy of 99.98%. The method was robust, reproducible, and specific with respect to the retention time of tofisopam.
Development and Validation of a Stability Indicating RP-HPLC Method for the Determination of Prucalopride succinate in Bulk and Tablet
Authors: Kanthale Sangameshwar B. , Thonte Sanjay S. , Pekamwar Sanjay S. , Mahapatra Debarshi Kar
Published: July 2021

A very simple, precise, economical, accurate, robust, and reproducible reverse phase-high-performance liquid chromatography method along with stability indicating attributes has been developed for estimating of prucalopride succinate (PRU) in both bulk and tablet formulation (PRUVICT 2). The estimation of the solutes was performed on a Grace C18 column of dimension 150 mm × 4.6 mm, 5 μm. PRU was eluted with acetonitrile: 0.02 M potassium dihydrogen phosphate in the ratio of 20:80 v/v in a 10 min isocratic mode at a flow rate of 1 ml/min at 30°C column temperature and monitored at a wavelength of 277 nm. The retention time of PRU was found to be 5.416 minutes. The Q2b validation of the analytical method revealed good linearity over the concentration range 2–12 μg/mL for IVA with r2 of 0.999. The mean recovery % over the three tested ranges of 50%, 100%, and 150% were found to be 100.173%, 99.077%, and 98.575%, respectively. In intra-day variability study, the % RSDs was detected to be 0.754, 1.032, and 0.482 whereas the inter-day variability study demonstrated % RSDs of 0.797, 0.559, and 0.524, respectively. The acid, alkali, boiled water, hydrogen peroxide, dry heat, and UV radiations based stress studies presented the formation of a variety of characteristic degradation products. The developed analytical method may be employed for the routine analysis of PRU in bulk and tablet formulations.
Development and Characterization of Liposomal formulation for ophthalmic delivery of Prednisolone Acetate
Authors: Joshi Hardik , Shelat Pragna , Dave Divyang
Published: July 2021

Liposomal vesicular drug carriers for ocular delivery have earned a wide potential nowadays. Prednisolone Acetate liposome as ocular drug carriers have been demonstrated to be a useful mode to ameliorate bioavailability and patient abidance. Liposome was prepared by lipid extruder method. Liposome were characterized for entrapment efficiency (EE %), vesicle size, surface morphology and in vitro drug release. An ex vivo corneal permeation study was performed to determine the level of drug in the external eye tissue of goat and an ocular irritation assessment was done by Hen’s Egg Test - Chorioallantoic Membrane (HET-CAM) method. The optimized formulation of liposome had shown acceptable viscosity (1.21 ± 0.03 cps), refractive index (1.47±0.001), osmolarity (303 ± 3 mOsm) and pH measurement (7.12 ± 0.09). Liposome as drug delivery carriers were evidenced to be a anticipating impendent to enhance corneal contact and penetration as well as retention time in the eye ensuing in a prolonged action and enhanced bioavailability. The results of stability study exhibited stable profile of developed liposomes.
Mechanistic Investigation on Anti-Nociceptive Potential of Bartogenic Acid Containing Barringtonia racemosa Fraction in Experimental Models of Pain
Authors: Patil Kalpesh R. , Mahajan Umesh B. , Goyal Sameer N. , Surana Sanjay J. , Patil Chandragouda R.
Published: July 2021

Barringtonia racemosa (B. racemosa) is a tropical medicinal plant possessing interesting biological activities. B. racemosa fruits are traditionally used in India for the treatment of pain, inflammation, and rheumatic conditions. Earlier, we have reported anti-inflammatory activity of ethyl acetate fraction (BREAF) obtained from B. racemosa fruits in animal models of inflammation and delayed-type hypersensitivity. The present study aimed to assess the anti-nociceptive activity of BREAF. Acetic acid-induced writhing test, and hot plate and tail immersion tests were employed to study the effect of BREAF on peripheral and central pain mechanisms, respectively. The involvement of opioid system was confirmed through naloxone antagonism. Formalin induced pain test was performed to assess the effect of BREAF on neurogenic and inflammatory pain components. Capsaicin induced pain models were used to investigate the involvement of transient receptor potential vanilloid 1 receptor. The BREAF reduced writhing episodes and delayed the onset of acetic acid-induced writhings. The raised percentage maximum protective effects by BREAF in hot plate and tail immersion tests suggest the efficacy of BREAF in pain alleviation. A reversal of the analgesic effect of BREAF following naloxone treatment indicates the involvement of opioid receptors. The BREAF also inhibited inflammatory and neurogenic components of formalin-induced pain. The inhibition of capasaicin induced pain to some extent by the BREAF indicates the possibility of involvement of TRPV1 receptors. This study reinforces the traditional use of B. racemosa in the treatment of painful conditions. However, further studies are reasonable to explore the detailed mechanism(s) of the anti-nociceptive action of BREAF.
Probiotic potential and safety characterization of Enterococcus hirae G24 isolated from indigenous raw goat milk
Authors: Rajput Kamni , Dubey Ramesh Chandra
Published: July 2021

In this paper, an investigation on lactic acid bacterial isolates from ethnic goat raw milk samples were examined for their probiotic potential and safety parameters. For this purpose, isolated bacterial cultures were screened based on certain parameters viz., sugar fermentation, tolerance to temperature, salt, low pH, bile salts, and phenol resistance. After that, these bacterial cultures were more estimated in vitro for auto-aggregation, cell surface hydrophobicity, response to simulated stomach duodenum channel, antibiotic resistance, and antimicrobial activity. Besides, probiotic traits show the absence of gelatinase and hemolytic activity supports its safety. The isolate G24 showed good viability at different pH, bile concentration, phenol resistance and response to simulated stomach duodenum passage but it did not show gelatinase and hemolytic activities. Isolate G24 was susceptible to amikacin, carbenicillin, kanamycin, ciprofloxacin, co-trimazine, nitrofurantoin, streptomycin, and tetracycline. Isolate G24 also exhibited antimicrobial action against five common pathogenic bacteria, such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogens, and Salmonella typhimurium. It displayed the maximum auto-aggregation, cell surface hydrophobicity to different hydrocarbons. Following molecular characterization the isolate G24 was identified as Enterococcus hirae with 16S rRNA gene sequencing and phylogeny. E. hirae G24 bears the excellent properties of probiotics.
Formulation, optimization and characterization of nanostructured lipid carrier of nitrofurantoin
Authors: Goswami Nilam , Patel Rakesh P.
Published: July 2021

Nitrofurantoin is effective against many urinary tract pathogens. It acts as bacteriostatic and/or bactericidal by inhibiting DNA-RNA protein& cell wall synthesis. Nanostructured Lipid Carriers (NLCs) of NFT was prepared by Hot Homogenization Process. Glyceryl Monostearate and Miglyol 812 were heated at 80ºC temperature on hot plate. In the melted lipid, drug was added with continuous stirring at high speed homogenization. Formulation NLC12B has % Entrapment efficiency 89.1 ± 0.5, PDI 0.11 ± 0.01 and mean particle size 237 ± 7nm represents narrow particle size distribution.  Spherical feature of NLCs with better uniformity without aggregation of Nitrofurantoin loaded NLC was confirmed by TEM. Moreover, efficient miscibility of drug in lipids was confirmed by the absence of intense and characteristic peak of NFT in XRPD. After 6 month storage at 2-8°C there was no significant changes in the PDI as well as mean particle size.
Development of Mebeverine HCl Prolonged release Mini-tablets by thermoplastic granulation technique
Authors: RAMANI KETAN B. , Patel Vipul
Published: July 2021

Mebeverine HCl is a BCS class-I drug and thus it possesses high solubility in aqueous media across the biological pH range. The marketed reference product is a multi-unit particulate system (MUPS) containing prolonged release pellets filled in hard gelatin capsule. In conventional manufacturing process, a huge quantity of solvents (aqueous and/or organic) is used to manufacture such dosage form. Additionally, it demands more processing time and efforts. Therefore, a prolonged release capsules dosage form of Mebeverine HCl was formulated using thermoplastic (melt) granulation technique without usage of any solvent. Prolonged release minitablets sized 2 mm in diameter were developed as per quality by design principles. A 23 full-factorial design of experiment was applied to optimize levels of drug release controlling ingredients which includes a hydrophobic meltable binder (hydrogenated castor oil) cum matrixing agent, a hydrophilic meltable binder (polyethylene glycol) which may act as pore former also, and a release controlling polymer (ethyl cellulose). The optimized formulation was found stable. Dissolution profiles of the optimized formulation were found similar to the marketed reference product in different media across the physiological pH range. In conclusion, the explored solvent less process was capable to manufacture the MUPS dosage form of Mebeverine HCl prolonged-release capsules, which is stable and pharmaceutically equivalent with the reference product. The developed process is more beneficial to small and medium scale industry, as it does not require any special and costly equipment, significantly decreases manufacturing cost and increases productivity compared to conventional process, which is mentioned in literature.
Bioactivity and Apoptotic Efficacy of the Purified Terpenoid Extract from the Moss Brachythecium Buchananii (Hook.) A. Jaeger against MG 63 Cells
Authors: Greeshma Geetha Mohandas , Manoj Gopal Sarayu , Murugan Kumaraswamy
Published: July 2021

Bryophytes are primitive non vascular plants. A little is explored regarding the medicinal effects of bryophytes on carcinoma. This study investigated the biological effects of purified terpenoids from Brachythecium buchananii on selected cell lines such as HeLa, MDAMB-231 and MG63 human osteosarcoma cells and also elucidating the regu­latory signaling pathways underlying the effects of terpenoids towards caspase cascade and the antioxidant enzyme system. The cell lines were treated with various concentrations of purified terpenoid extracts interms of evaluating viability (MTT assay). Interestingly, MG63 cell lines showed poor viability as compared to other ongo cells and was subjected to further molecular evaluations. Migration and invasion assay results using wound-healing and transwell assays, respectively reveal the pro-antimetastatic potential of the purified terpenoids from the moss. The flow cytometry study substantiated terpenoid induced apoptosis in MG63 cells. Cell cycle analysis revealed the significant increase in the number of cells arrested at the S growth phase. Terpenoid extract also displayed DNA fragmentation in the cells. Western blot analysis revealed the down regulation of the anti‑apoptotic proteins Bcl‑2, pro‑caspase 3 and over expression of the pro‑apoptotic protein Bax. In addition, the caspase cascade profile of the terpenoid extract substantiated their efficacy in tumour inhibition. Thus, the overall results confirmed the biological features of terpenoid induced apoptosis in the MG63 cells.
Carboxymethylation of Karaya gum: application in gastroretentive drug delivery for sustained release of model drug
Authors: Verma Amit , Sachan Neetu , Verma Anurag
Published: July 2021

Karaya gum (KG) is one of the least soluble of the gums. It does not dissolve in water to give a clear solution but instead absorbs water rapidly to form viscous colloidal sols. Carboxymethylation of Karaya gum is expected to improve its aqueous solubility and gelling behavior. Another objective of the research is to evaluate the potential of carboxymethylated Karaya gum (CMKG) as drug release modulator (in acidic dissolution medium) when combined with HPMC K15M based polymeric matrices bearing Propranolol HCl. In the present study, KG was carboxymethylated using Williamson Ether synthesis. FTIR spectroscopy confirmed the formation of CMKG. The prepared CMKG was used in conjunction with HPMC K15M as a polymer matrix in the formulation capsule dosage form, using Propranolol HCl as model drug. The filled capsules were then coated with Gelucire 43/01 to convert them into hydrodynamically balanced (HBS) capsule dosage form. Dextrose & fructose were also added to the drug-polymer mix as osmogen to facilitate the drug release. The degree of substitution of CMKG was found to be 0.87. HBS capsule dosage forms remained buoyant on 0.1 HCl for up to 6 hr, the buoyancy was attributed to the Gelucire 43/01 coating around the capsule shell. From the experimentation it was observed that CMKG, when mixed with HPMC K15M at 1:3 ratios, extended the release of model drug from HBS capsule dosage forms in 0.1 HCl. At CMKG: HPMC K15M ratio 2:1, release of Propranolol Hydrochloride from hydrodynamically balanced (HBS) capsules revealed fast drug release in 0.1 HCl. From the observations it is evident that KG is amenable to carboxymethylation to form CMKG. It is also evident that it is advantageous to combine CMKG with HPMC K15M as release modulator to retard the release of Propranolol HCl in acidic dissolution medium.
Antioxidant and Cardiac Enzyme Marker Studies of Thevetia peruviana Seed Hydro-Methanol Extract in Wistar Male Albino Rats
Authors: Nesy EA , Padikkala J , Mathew L
Published: July 2021

Thevetia peruviana seed kernels are used for suicide attempts in many countries centuries back. The aim of the present study was to evaluate the level of toxicity exposure of seed kernels by acute and subacute studies on male wistar rats taking antioxidant enzyme levels in the vital organs like liver, kidney, heart and brain tissues myocardial marker enzyme levels in serum. Results revealed that antioxidant enzyme (SOD, GPX, GSH) levels was normal in the lower groups (25, 50 mg/kg), but drastic hike was observed in CKMB and LDH cardiac biomarker enzyme levels in 100 mg/ kg groups. In the liver tissues of group IV animals a significant dose dependent increase was observed in the activities of SOD (3.15 ± 0.58), GPx (46.55 ± 4.79) and GSH activity (18.20 ± 0.56). In kidney homogenates SOD and GSH level showed a statistically insignificant (p > 0.05) elevation, but the increase in GPx level shown by group IV animals (41.50 ± 7.04) was significant (p < 0.05) The activities of SOD in brain homogenates were increased significantly in group III (2.17 ± 0.24) and group IV (2.51 ± 0.27) animals. The GPx enzyme level also increased dose dependently (p < 0.01), but the level of GSH was found an insignificant hike. The heart, supposed to be the most adversely affected organ on cardiac glycoside administration, showed undisturbed values of enzyme levels. A noticeable elevation was observed in the serum CKMB and LDH enzyme levels in a dose dependent manner, but the extract did affect only the higher dosed animals (100 mg/kg) significantly (p < 0.05), In contrary to that, tissue homogenates of subacute animals under study showed a markedly significant hike in both CKMB and LDH levels. In conclusion, the level of toxicity and safety margin is very narrow, and the seeds really take lives of organisms, whose intake is accidentally or deliberately.
In vitro Antioxidant Potentiality of Purified Anthocyanin from Floral Petals of Wild Balsam Species
Authors: Arathy Rajendranpillai , Murugan Kumaraswamy , Dinesh Babu Kalekkal Vasupillai , Manoj Gopal Sarayu
Published: July 2021

Phenolics are the largest group of phytochemicals ubiquitous in plant species with considerable interest economically. Recently, search of novel polyphenols increasingly becomes an area of intensive pharmacological research due to their multiple bioactive features such as antioxidant, antimicrobial, anti-carcinogenic, anti-viral and anti-inflammatory potentialities.  Anthocyanins are flavonoid group of polyphenols, a group predominant in flowers, fruits and vegetables. The flavonoids, perhaps the unique single group of phenolics in foods, comprise a group of over 4200 C15 aromatic molecules with multiple structural patterns. The functions of anthocyanins as medicinal have been well-accepted in folk medicine throughout the world. In fact, these molecules are connected to an amazingly broad-based range of health benefits. In this juncture, the aim of this work was to evaluate the antioxidant activities of purified anthocyanin from wild balsam species. Initially, anthocyanin was extracted from floral leaves of wild balsam species and purified by chromatographic techniques. Subsequently, it was subjected to NMR and LC MS analysis. The major fractions identified were hesperidin, dimethoxy antirrhinin and trimethoxy antirrhinin. Further, the anthocyanin extracts were subjected to in vitro protocols like 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation, DPPH scavenging assay, ferric reducing antioxidant power (FRAP), beta carotene bleaching assay, metal chelating and H2O2 scavenging power. Interestingly, ABTS, FRAP analyzes yielded significant results as compared to others. The data were comparable with that of synthetic antioxidants like ascorbate and catechin. Meanwhile, beta carotene and H2O2 scavenging assay showed moderate results. DPPH and metal chelating protocols displayed the values 71% and 64% respectively at 25 µg/ml concentration. This study provides model systems for the evaluation of natural antioxidants like anthocyanin. Future in vivo clinical studies are warranted to confirm the obtained data.
Screening of in vitro antiviral activity of purified terpenoid extracts of selected sea weeds against chikungunya virus
Authors: Sumayya Sabira Siraj , Lubaina Abdulhadeef Shereefa , Murugan Kumaraswamy
Published: July 2021

Currently, the search of novel phytochemicals with unique biological potentialities is a pre-requisite for the designing ideal drugs for the human kind. Sea weeds are bioresources with a broad spectrum of medicinal properties with minimal side effects. Kerala, the Southern state of India reported high incidence of Chikungunya virus (CHIKV) infections in the last several tears. No specific virucidal therapy or effective vaccines are available. This emphasizes the need of searching for phytochemicals as drugs with less cost and more effective. Therefore, an attempt was made in screening purified terpenoid extracts of selected sea weeds as anti-CHIKV potential. In this study the terpenoids composition from the red algae Hypnea musciformis, Kappaphycus alvarezii and Gracillaria dura were identified and analyzed by thin layer chromatography and Gas chromatography- Mass spectrum. The methanolic extract of seaweeds was purified by column chromatography and each fraction was eluted by using petroleum ether and ethyl acetate as solvent combination. The analysis of the purified fraction of H. musciformis and K. alvarezii revealed the presence of 8 terpenoid fractions, and G. dura showed only 4 major components respectively. Vero cell lines were employed in the antiviral assays, infected to CHIKV, and treated with varied doses of purified terpenoid extracts. In the antiviral activity, terpenoid extracts of G. dura showed remarkable and promising EC50 inhibitory effect at 1.25 μg/ml. Further, the terpenoid extracts displayed efficient virucidal activity against CHIKV (inhibit around 90%) with 5 μg/ml dosage. As the last phase, terpenoid extracts added at time intervals of 0, 1, 2, 3 post-infection periods still maintained a significant inhibitory potential against CHIKV viral replication. Thus, the overall study suggests that the terpenoid extracts of G. dura may be effectively used in the prevention and treatment of CHIKV infections. Clinical studies may be warranted for designing a promising new anti-CHIKV drug.
PROTECTIVE EFFECT OF HYDRO-ALCOHOLIC EXTRACT OF DRIED FRUITS OF HELICTERES ISORA IN DEXTRAN SULFATE SODIUM (DSS) INDUCED ULCERATIVE COLITIS IN EXPERIMENTAL WISTAR RATS
Authors: Murudkar Prajakta , Kolhe Swati , Tembhurne Sachin
Published: July 2021

Ulcerative colitis is a most common form of inflammatory bowel disease (IBD) which mainly affect colon. The treatment of ulcerative colitis depends upon severity of the diseases. The aim of the present study was to determine the effect of hydroalcoholic extract of dried fruits of Helicteres isora in dextran sulfate sodium induced ulcerative colitis in experimental wistar rats. In this study wistar rats of either sex were divided into five experimental groups, where control group recived only distilled water. Group 2 was negative control group which received 4% dextran sulfate sodium (DSS) from drinking water between 15th to 21st day. Group 3 received low dose of hydroalcholic extract of Helicteres isora (HI) at a dose 100mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. Group 4 received high dose of hydroalcholic extract of Helicteres isora (HI) at a dose 200mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. In group 5 sulfasalazine was used as a standard drug at a dose 100mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. Twenty four hours after treatment animals were sacrificed and further macroscopical, biochemical, histopathological evaluation was done and all the results were compare with control at p<0.05 significant value.
In-silico Study of Molecular Properties, Bioactivity and Toxicity of 2-(Substituted benzylidene)succinic acids and Some Selected Anti-Inflammatory Drugs
Authors: Kuchana Madhavi , Pulavarthi Maneesha , Potthuri Sasikala , Manduri Vyshnavi , Jaggarapu Vijaya Durga
Published: July 2021

Succinic acid and its derivatives have many important uses, especially in pharmaceutical and polymer industry. The 2-(substituted benzylidene)succinic acids also known as substituted phenylitaconic acids are utilized in the synthesis of some lignans, lignanamides and renin inhibitors.  In view of this, the present in-silico study aimed to calculate the molecular properties, bioactivity score and toxicity of several benzylidenesuccinic acids as well as some selected anti-inflammatory drugs by computational methods.  The study revealed that all the compounds obeyed Lipinski’s rule of five, indicating drug likeness properties. The bioactivity data revealed that the 2-(substituted benzylidene)succinic acids were active as Nuclear receptor ligands, Enzyme inhibitors, GPCR ligands and Ion channel modulators. Among all, 2-(3,5-di-tert-butyl-4-hydroxybenzylidene)succinic acid was predicted as non-toxic with better in-silico molecular properties and bioactivity as Nuclear receptor ligand, Enzyme inhibitor, GPCR ligand, Ion channel modulator and Protease inhibitor compared to some of the predicted anti-inflammatory drugs.
Design and Evaluation of Lovastatin Solid Dispersions Incorporated Trilayer Matrix Tablets
Authors: Shanthi Priya Chinthala , Reddy Tummaluru Ramamohan
Published: July 2021

The current work is aimed to design, prepare and evaluate the trilayer matrix tablets incorporated with lovastatin solid dispersion (SD) for extend drug release. The lovastatin SD prepared by using solvent evaporation technique with varying amounts of polymers (GMS II, Soluplus, Kolliphor ELP, PEG 2000 and Urea) for enhancing the drug solubility. All the formulations examined for physicochemical parameters are within the permissible limits. The optimized SD formulation was incorporated into trilayer matrix tablets which were prepared using different polymers (HPMC 15M & K100M, Chitosan, xanthan gum) by direct compression method for sustaining the drug release. The drug dissolution of optimized lovastatin SD formulation SD15 (drug, soluplus and SLN) was 99.88±5.32% within 60 min which is higher than pure drug 47.33±2.25% and other formulations. The FT-IR, XRD and SEM data assure the compatibility of drug and excipients and amorphous nature of lovastatin. The solid dispersions were further incorporated in to trilayer matrix tablets with active layer and barrier layers. Eight formulations of lovastatin trilayer matrix tablets (AF9-HF9) designed and checked for pre compression parameters. Formulation GF9 demonstrated highest drug release of 99.41±5.28% for 24 hours sustainably over an extended period of time and excellent flow properties. The release order kinetics data indicate the zero order release with highest R2 of 0.9957 for GF9, superior than market extended release formulation (R2=0.9934). All the formulations showed best fit to Higuchi model and Korsmeyer-Peppa’s model indicating diffusion and non-Fickian diffusion process of drug release. GF90 was found to be stable for 180 days at accelerated conditions. Hence the solubility, dissolution rate of lovastatin was enhanced by SD technique further incorporated in to trilayer matrix tablets for sustainable extended drug release upto 24 h.
Protective effect of Barringtonia racemosa Ethyl Acetate Fraction against Cisplatin-induced Nephrotoxicity in Rats
Authors: Patel Rachna B. , Mahajan Umesh B. , Goyal Sameer N. , Surana Sanjay J. , Patil Chandragouda R. , Patil Kalpesh R.
Published: July 2021

Cisplatin is a major antineoplastic drug for the treatment of solid tumors. Nephrotoxicity is dose- limiting side effect associated with clinical use of cisplatin. The present study was executed to determine whether bartogenic acid containing fraction of Barringtonia racemosa fruits (BREAF) possesses a nephroprotective effect against cisplatin-induced nephrotoxicity in rats. Furthermore, the study was also aimed to explore the mechanisms underlying this effect of BREAF. The BREAF was orally administered at the doses of (2, 5 and 10 mg/kg) for five consecutive days following single dose administration of cisplatin (5 mg/kg, i.p.). Treatment of animals with cisplatin resulted into the significant body weight changes, oxidative stress, elevated levels of serum biomarkers and histological alterations in the kidney architecture. The BREAF administration reduced relative body weight and organ weight changes in cisplatin-treated rats. The BREAF exhibited nephroprotective effect through the significant reduction of cisplatin-induced rise in the serum creatinine, and blood urea nitrogen levels as well as renal levels of malondialdehyde (MDA) the makers of lipid peroxidation. Additionally, the treatment with BREAF resulted into the increased renal levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activity. Histopathological examination established the nephroprotective effect of BREAF. In conclusion, the anti-oxidant, and anti-inflammatory effects of BREAF has important role underlying its nephroprotective effect.
Formulation Development of Rotigotine Transdermal System Using Dot-Matrix Technology
Authors: Prajapati Shailesh T. , Mandli Vipulbhai A.
Published: July 2021

The purpose of this research was to prepare and evaluate drug-in-adhesive type patches of rotigotine using dot-matrix technology, which is the new generation of drug-in-adhesive transdermal delivery system (TDS) that deliver drug therapy through less patch surface area and without compromising adhesion. Preformulation studies, like solubility in permeation enhancers, compatibility study, transmission study, uptake study, and crystallization study of rotigotine in various pressure-sensitive adhesive (PSA) polymers were performed. Transdermal system was prepared by solvent casting method. Central composite design (CCD) was chosen for optimization of the formulation. Design of experiment (DoE) was used to study the impact of critical formulation parameters, like silicone adhesive concentration, povidone K29/32 concentration, and propylene glycol concentration. Crystallization study of rotigotine in different PSAs suggested that crystal inhibitor is required to load drugs above 5%. Selection of optimum batch was made using a constraint-based graphical optimization technique. The optimum batch exhibited desired in vitro adhesion parameters, like peel, tack, shear, and permeation rate, which is suitable for 3 days’ wear properties and desired permeation rate. The optimum batch was evaluated for appearance, weight of matrix, thickness, % assay of drug content, in vitro adhesion testing, cold flow study, and ex vivo skin permeation studies. Backing film Scotchpak 9730 and release liner Scotchpak-1022 was selected based on transmission and uptake study of rotigotine. Stability study indicates that developed formulation remains stable. The present research confirms the feasibility of developing rotigotine transdermal system using novel technology.
COVID-19: An Update on therapeutics and Clinical trials
Authors: Pathak Kamla , Pathak Devender , Yadav Ramakant , Kumar Raj
Published: July 2021

Corona viruses are a large family of viruses that cause illness ranging from the common cold to more severe diseases. A novel coronavirus (nCoV) is a new strain that has not been previously identified in humans. On 30 January 2020, the WHO Director-General declared the novel corona virus (COVID-19) outbreak a public health emergency of international concern. Many fatalities have occurred and continue to happen. Despite staggering research efforts for therapeutics, complete cure is still a distant dream. The write up updates the treatment approaches utilized in clinical settings across the globe and the clinical trials registered in the Federal register and WHO register for drugs and vaccines to combat the pandemic.