bluuebunny/crossref_metadata_2025 huggingface dataset:
Solubility improvement and Dissolution enhancement of Simvastatin using Fluidized Hot-Melt Granulation Technique
Authors: Modi Deval J. , Shastri Divyesh H. , Shelat Pragna K.
Published: June 2022

A fluidized hot melt granulation (FHMG) technique was used to enhance the solubility and dissolution of simvastatin. Employing meltable hydrophilic binders and then converting the melt dispersion into flowable and compressible dispersion granules to yield a rapidly dissolving tablet formulation. Granules prepared by using hydrophilic polymer polyethylene glycol 4000 or 6000, Gelucire 50/13 or 44/14, and Poloxamer 188 or 407, spray-dried lactose as a fluidized substrate. The binder used for spray granulation in this technique was a mixture of molten Gelucire 50/13 and simvastatin. Phase Solubility studies showed an increase in solubility ratio of 1:4 for Simvastatin: Gelucire 50/13. The prepared granules were characterized using FTIR, and DSC spectra exhibited drug excipients compatibility. XRD data exhibited a partial loss of crystallinity as indicated by significantly less intensity of simvastatin peak in a sample than pure simvastatin. Tablets with the faster dissolution of simvastatin (98.99% of the drug release with 30 minutes). This was achieved with lactose/MCC as filler. A significant enhancement in-vitro dissolution profile of the melted granules was observed compared to the pure drug and marketed product. Therefore, the results confirmed the high potential of the FHMG technique to produce granules with enhanced drug solubility and release rate.
Nephroprotective Activity of Diospyros Malabarica (Desr.) Kostel against Gentamicin induced Nephrotoxicity in Rats
Authors: PURANE LAXMIKANT MARUTI , Vidyadhara Suryadevera
Published: June 2022

Diospyros malabarica (Desr.) Kostel (DMDK) plant is abundantly grown, and various parts are traditionally used for treating diarrhea, wound, cancer, diabetes, ulcer, and renal diseases. However, its medicinal importance is not assessed. Further, it was observed that there is no pharmacological standard established on fruits of DMDK. Therefore, the present study investigates the nephroprotective activity of DMDK fruits against the gentamicin (GEN) induced nephrotoxicity model. Ethanolic extract of fruits of DMDK (EEFDMDK) was screened for its nephroprotective activity against GEN (100 mg/kg i. p.) induced nephrotoxicity in rats by standard method. The protective property of EEFDMDK was assessed by measuring the body weight (BW) of animals before and after experiments and calculating a change in body weight (CIBW) of animals, the weight of kidney (WK), urine output, estimating biochemical parameters, and histopathological observations of a kidney. Our data showed that GEN administration resulted in significantly increased levels of biochemical parameters. Pretreatment with EEFDMDK normalized the GEN-induced increased levels of biochemical parameters. We also observed that EEFDMDK significantly protect the rat kidneys from GEN-induced histopathological changes. Similarly, EEFDMDK restored BW reduction of animals and prevented an increase in WK of animals. The possible mechanism underlying this effect is mediated collectively through the presence of polyphenols like flavonoids, tannins, and the diuretic effect of the DMDK.
Optimization of Colon Specific Drug Delivery System for Ornidazole using modified gum
Authors: Fenin Vikas , Kachawa Vijay Singh , Jain Chandra Prakash
Published: June 2022

The present study aimed to optimize a colon-specific formulation of ornidazole for the treatment of Crohn's disease and intestinal amoebiasis. Firstly carboxymethyl xanthan gum was prepared from xanthan gum reacting with monochloroacetic acid in alkaline conditions using the Williamson synthesis method. Fourier transform infrared spectrophotometer (FTIR) spectroscopy confirmed the formation of carboxymethyl xanthan gum. The differential scanning calorimetry (DSC) revealed the crystalline nature of carboxymethyl xanthan gum. A 32 full factorial design was used for optimization. The independent variables employed were the amount of Carboxymethyl Xanthan gum and the amount of hydroxy propyl methyl cellulose (HPMC), each at three levels. Drug release studies were carried out in various media [pH 1.2, 7.4, and 6.8]. The optimized formulation consisting of Carboxymethyl Xanthan gum (66 %) and HPMC (22%) released a small fraction of drug at pH 1.2 and pH 7.4, whereas significant drug release was observed at pH 6.8. The results of the study established Carboxymethyl Xanthan gum compression coated tablet to be a promising system for the colon-specific delivery of ornidazole to treat active Crohn's disease and intestinal amoebiasis.
Formulation Development, Quality Evaluation and In Vitro Antioxidant Activity of a Polyherboceutical Composition
Authors: Garg Naveen Kumar , Katara Antariksh , Mathur Mukul
Published: June 2022

Polyherbal preparations have been used for health management for decades. Allopathic dosage forms are prominent due to their ease of administration and stability, but polyherbal formulations are also pharmacologically effective and show useful therapeutic activity. As a result, extracts of a six potent herbs with anti-oxidant and anti-hypertensive properties were chosen and formulated in a capsule dosage form. This study aims to investigate the anti-oxidant activity of a polyherboceutical formulation. A polyherboceutical formulation were prepared using six ingredients, and quality control parameters were performed, including organoleptic, physio-chemical, qualitative, and quantitative estimation of secondary metabolites and microbial load. The formulation was possessed a good anti-oxidant activity with 7.87 mg/mL for IC50 and 0.5 of absorbance on 8.6 mg/mL concentration found with DPPH free radical scavenging activity and ferric-ion reducing activity simultaneously.
Screening of synergistic antistress activity of Phyllanthus niruri leaves and Sapindus mukorossi fruits
Authors: Malik Nazia , Jat Rakesh K. , Bhikshapathi Darna
Published: June 2022

Phyllanthus niruri leaves and Sapindus mukorossi fruits have been traditionally used as anti-inflammatory, anti-pyretic and analgesic, anti-fungal, anti-microbial, anti-bacterial and antiparasitic, expectorant, emetic, anti-cancer, mood elevator, and as hepatoprotective. The present study was designed to investigate the anti-stress activity of combined extract of P. niruri leaves and S. mukorossi fruits employing various activities using experimental animals. Rats and Mice were separated into five groups, consisting of six animals each. Methanolic extract of P. niruri leaves (MEPNL), aqueous extract of S. mukorossi fruit (AESMF), and combined extract (MEPNL+AESMF) were prepared and anti-stress activity was investigated by Anoxia induced stress in mice, Immobilization stress in rats, and Swimming endurance test in mice. Combined extract (400 mg/kg, p.o.) exhibited remarkable effect as it delayed onset of convulsion time in anoxia stress model when equated to individual extracts. In swimming endurance test, combined extract (400 mg/kg, p.o.) displayed significant effect as it enhanced swimming time in mice when compared to MEPNL (400 mg/kg, p.o) and AESMF (400 mg/kg, p.o). Combined extract has remarkably reduced the serum levels of glucose, triglycerides, cholesterol, blood urea nitrogen, and cortisol in rats as equated to control. Combination of extracts has produced remarkable and protective effects on organs such as liver, adrenal gland, spleen, and testes. Present study showed that the combined extract of P. niruri leaves and S. mukorossi fruits possessed significant anti-stress action, which was found to be higher than the individual extracts. This indicates the synergistic anti-stress efficacy of the combination of extracts. However, future studies are essential to focus on the cellular mechanism of quantitative phytochemical constituents and ascertain the precise mode of action involved in its anti-stress property.
Development and Characterization of Gastroretentive Drug Delivery System of Olmesartan Medxomil
Authors: Pandiya Harshda , Sharma Chandra S.
Published: June 2022

The objective of the study was to develop an optimized gastro retentive drug delivery system of Olmesartan Medoxomil. The tablets were formulated by direct compression using HPMC K15M, HPMC K4M, Xanthan Gum and PVP K30. Sodium bicarbonate was used as the gas generating agent to reduce the floating lag time. The drug-polymer interaction was evaluated by Fourier Transform Infrared Spectroscopy (FTIR) and DSC study. The FTIR and DSC study indicated the lack of drug-polymer interaction. The formulated tablets were evaluated for hardness, weight variation, thickness, floating capacity, swelling index, drug content, in vitro dissolution study. Formulations were following nonfickian (anamalous) diffusion as the release mechanism from all the floating tablets prepared with various polymers.
Endocrine Disruptors (EDs) regulatory waves: A frictional lens perspective on regulated and emerging markets
Authors: Tripathy Swagat , Murthy Padala N. , Patra Bibhu P. , Sanduria Sumit , DUREJA HARISH
Published: June 2022

Endocrine-disrupting chemicals (EDCs) are significantly costing humanity, which upshots the increase in disease and disability. However, unlike other toxicant classes — EDCs have yet to be cataloged onto regulations in a mature way across the globe. This manuscript intends to serve up as a compendium of information that endows with an overview of existing regulatory frameworks and policies those deal with EDCs. In particular, it spotlights on frameworks that explicitly address EDCs (i.e., frameworks that consider both adverse effects and their endocrine causes in the assessment of chemical(s)). Precisely frameworks from 12 countries have been acknowledged and information crucial to understanding the basic functioning has been summarized. This information encompasses the general procedures/practices, criteria, and data requirements for EDCs. An attempt has been made to scan not only economic, regulatory policies available for regulated (USA, Europe, Australia, and Japan) and emerging markets (China, Brazil, South Africa, India, Bangladesh, Korea, and Malaysia), but also illustrate perspective for improvement.
Solvent Free Synthesis and Characterization of Few Metal Complexes of Schiff Base Derived from 2-Amino-5, 6-dimethyl Benzimidazole and Syringaldehyde
Authors: Undegaonkar Mahesh G , Sinkar Sadashiv N , Bhosale Vijay N , Mirgane Sunil R
Published: June 2022

A solvent-free synthesis of bidentate Schiff base ligand was carried out by treating 2-Amino-5, 6-dimethyl benzimidazole with Syringaldehyde in 1:1 molar proportion in a scientific microwave oven. The excellent yield was obtained after purification. Few metal complexes of Schiff base were synthesized by using Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Ag(I) metal salts in microwave oven under solvent-freecondition.
All metal complexes showed distinct color at the end of the reaction, and the melting point of
each complex preliminary confirmed the formation of the product. A detailed characterization of both Schiff
base and its representative metal complexes was carried out by several analytical and spectral techniques,
including elemental analysis, Infrared (IR) spectroscopy, 1
HNMR spectroscopy, liquid chromatography–
mass spectrometry (LCMS), UV spectroscopy, and TGA. The spectroscopic analysis supports the predicted
structure of the parent Schiff base ligand. Bioactivity of Schiff base and respective metal complexes was
studied against Escherichia coli, Staphylococcus aureus and Salmonella typhi showing significant bioactivity
of the metal complexes and Schiff base ligand.
Evaluation of Anti-inflammatory Activity of Trichosanthes dioica Roxb. Seeds
Authors: Arora Rashmi , Singh Gill Naresh
Published: June 2022

Inflammation a complex disease associated with various symptoms. These symptoms can be managed with non-steroidal and steroidal anti-inflammatory drugs, which on long term use lead to severe side effects.  To overcome this problem, natural products are used as an alternative source of the discovery of new entities to be used as compounds anti-inflammatory compounds. Trichosanthes diocia (T. diocia) belongs to Cucurbitaceae family. T. dioica a dioecious perennial herbaceous vegetable is rich source of vitamin C and minerals. In addition to fruits, leaves and tender shoots have been used in the indigenous system of medicine. The objective of the present study was to evaluate the anti-inflammatory activity of methanolic extract of Trichosanthes dioica seeds for scientific validation of the folklore claim of the plant. The extract was evaluated at three different concentration of 100, 200 and 400 mg/kg, p.o. Significant dose dependent anti-inflammatory activity was observed which was comparable with that of the standard drug indomethacin at dose of 10 mg/kg.
Advanced Derivative Spectroscopic Method for Estimation of Montelukast and Bilastine in Their Tablet Dosage Form
Authors: Detroja Kinjal , Vekaria Hitesh
Published: June 2022

Aim of present work is development and validation of advance derivative spectroscopic method for estimation of Montelukast (MON) and Bilastine (BIL) in their tablet dosage form. This tablet dosage form is used as an anti-asthmatic and allergic rhinitis. The developed method can be applied for simultaneous estimation of Montelukast and Bilastine in their combined dosage form. For this advanced derivative method, the absorbance at 226.8 nm (ZCP of Montelukast) and 326.4 nm (ZCP of Bilastine) was used for the estimation of Montelukast and Bilastine, respectively. The developed method is validated by ICH Q2R1 guidelines with validation parameters like linearity, LOD, LOQ, accuracy, precision, robustness, ruggedness and assay were performed using this guidelines. The method was found to be linear in the concentration range of 2-14 µg/ml for Montelukast (R2=0.999) and 4-28 µg/ml for Bilastine (R2=0.9997). LOD and LOQ found 0.1216 and 0.3686 for MON and 0.3406 and 1.0320 for BIL. Precision study were carried out by comparing on 3 different concentrations and result of their %RSD were <2%. Robustness study carried out by change in scanning speed and change in methanol manufacturer and Ruggedness study carried out by different analyst. Assay study was performed using tablet formulation. The developed method was utilized for simultaneous estimation of Montelukast and Bilastine for its tablet dosage form.
Development and validation of RP-HPLC method for In-Vitro Dissolution Testing of Bilastine and Montelukast Sodium Tablets
Authors: Chandra Umesh , Kumar Manish , Sharma Shrestha , Gupta Pankaj
Published: June 2022

The objective of this experimental work is to develop and validate a reverse phase high performance liquid chromatographic (RP-HPLC) method which is capable for quantitatively estimation of Bilastine (BLS) and Montelukast (MTK) content present in dissolution media with accurately and precisely. A simple, fast, specific, rugged and reproducible analytical method was developed and validated on a Shimadzu HPLC equipped with diode-array detector. A Hypersil BDS C18-Column (100 mm x 4.6mm, 3µm) and 0.1%v/v Triethylamine buffer (pH-3.0):Acetonitrile used as mobile phase with flow rate 1.0 ml/min in gradient mode.The column oven temperature and sample cooler temperature was set to 40°C and 25°C respectively. Injection volume was10µL and chromatograms were recorded at 220nm. The optimized conditions for dissolution testing includes USP type-II apparatus at 75 rpm with 900mL, 0.5% w/v sodium lauryl sulphate media at 37.0 ± 0.5°C. Under above conditions the retention time of Bilastine and Montelukast was 7.23 and 1.84 min respectivelywithout any interference of dissolution media or any other degradant at the RT of both drugs. The calibration curve was found linear with R2 value 0.99987 and 0.99985 for BLS and MTK respectively and sample was found stable in dissolution media up to 12 hours. The analytical method was validated as per ICH guidelines with respect to specificity, precision, linearity, accuracy, stability in aqueous solution and robustness.The proposed method was found useful for the routine analysis of dissolution samples for quality control purposes.
A Stability Indicating RP-HPLC Method Validation for simultaneous estimation of Azelnidipine and Telmisartan in a fixed-dose combination
Authors: Kumar MANISH , Chandra Umesh , Garg Arun , Gupta Pankaj
Published: June 2022

The present investigation deals with the validation of the developed method using RP-HPLC for simultaneous estimation of Azelnidipine as well as Telmisartan in a fixed-dose combination (FDC). The method was developed using RP-HPLC, Inertsil C-18 Column with 150×4.6 mm× 5 µm at column oven temperature 40°C, flow rate 1.5 mL/min, volume 10 µL and run time 12.0 minutes at 254 nm using Acetonitrile and buffer as mobile phase in various ratio. The developed protocol was most accurate, repeatable, and detectable towards Azelnidipine and Telmisartan in combination without any unwanted interference. When evaluated on various parameters like system suitability, precision, accuracy, linearity, robustness, force degradation study it can be concluded that the method is efficient in separating the API from its degradants and can be utilized for analyzing the samples of Azelnidipine and Telmisartan.
Efficient Production of Yeast Cu-Zn Superoxide Dismutase in the Periplasm of Escherichia coli by Co-expression of Skp Molecular Chaperone
Authors: Suryawanshi Yogesh , Gupta Surekha , Mange Hiral , Tripathi Manisha
Published: June 2022

Co-expression is a simultaneous expression of two or more proteins. Molecular chaperons are proteins that naturally produced in the cell and have an important role to restrain aggregation of non-native protein production. Co-expression of target protein along with molecular chaperone is an efficient way to overcome the problems faced during expression of recombinant proteins. The present study aims at co-expressing protein that is highly useful in cosmetics, Superoxide dismutase in periplasm of E. coli with molecular chaperone Skp. To maintain expression levels between Superoxide dismutase (SOD) and Skp, both proteins were placed under the control of different promoter and terminator systems in a single vector. Effect of co-expression of Skp chaperone on cell growth, SOD protein yield and SOD enzyme activity were evaluated. Skp co-expression found effective in all three aspects. The yield of Cu-Zn Superoxide dismutase increased from 30.92mg/L to 52.01mg/L when Skp chaperon is co-expressed. No detectable free SOD subunits were observed on western blot, which established method of Skp co-expression could be applied to tackle problem of unprocessed free protein subunits while expressing recombinant protein in E. coli periplasm.
Development and Evaluation of Manidipine Loaded Self-Nanoemulsifying Drug Delivery System by Box-Behnken Design
Authors: Jayapal Nallapu , Vishnu Yamsani V.
Published: June 2022

The current study aims to formulate an anti-hypertensive drug manidipine self-nanoemulsifying drug delivery system (SNEDDS) employing different novel polymers to enhance solubility and drug release manidipine. The optimal concentration of excipients chosen based on solubility study further confirmed by self-emulsification region of pseudo ternary phase diagram. Manidipine SNEDDS optimized employing Box-Behnken Design (BBD) through the study of factors - the amount of capryol 90(A), cremophor RH40 (B) and triacetin (C) and responses -droplet size (Y1), zeta potential (Y2), and cumulative percentage of drug release after 60 min(Y3). All formulations were evaluated for particle size, zeta potential, polydispersity index, entrapment efficiency, drug content, and in-vitro drug release. The optimized formulation was characterized for FTIR, SEM, and stability studies. The study indicates that manidipine optimized formulation MF11 comprising of capryol 90 (40.0%), cremophor RH40 (10.0%) and triacetin (30.0%) exhibited minimum droplet size (76.5 ± 2.87), best zeta potential (-24.7 ± 1.31mV) and entrapment efficiency (98.23 ± 1.74%) content uniformity (99.12 ± 1.28%) maximum drug release (98.79 ± 1.68%). The FTIR studies of MF11 indicated no significant interaction amid the drug and formulation excipients. The SEM data revealed that particle size is in the nanometer range with a zeta potential value >5 mV indicating higher absorption and stability. Accelerated stability studies indicated the formulation to be stable for 3 months. Hence the results revealed that application of SNEDDS formulation technique for manidipine increased solubility and drug release.
Design And Characterization Of Ceritinib Self- Nanoemulsifying Drug Delivery Systems (SNEDDS)
Authors: Katuri Sujitha , Bhikshapathi Darna
Published: June 2022

The main objective of the current study was to develop ceritinib SNEDDS for the improvement of solubility, permeability and drug release. Solubility of ceritinib was studied in various oils, surfactants and co-surfactants and based on its maximum solubility an oil, surfactant and co-surfactant were chosen (captex355,tergitol and propylene glycol) and mixed in varying ratios , the ratios with no phase separation, maximum transmittance and clear in appearance  were identified and used for plotting  pseudo tertiary phase diagram. Fifteen SNEDDS formulations were selected from miscible regions of pseudo ternary phase diagram subjected to thermodynamic stability testing. Formulations that passed stability testing were evaluated for % transmission, drug content and in vitro drug release analysis. The final optimized formulation was analysed for particle size, Z average and zeta potential followed by FTIR and SEM analysis. Formulation F13 with maximum drug release of 98.9% in 60 minutes that is higher than 48 % of pure drug is considered the optimised formulation. The particle size, Z average and zeta potential of the ceritinib SNEDDS formulation F13 were 144  nm, 132 nm and -7.2 mV respectively. The FTIR and SEM studies do not indicate any drug excipient interaction and confirm uniform drug distribution. The formulation subjected to accelerated stability study is proved to be stable over a period of six months. The results indicate ceritinib SNEDDS formulations can be designed in order to enhance the solubility of ceritinib and thereby increase in its absorption rate and drug release.
FORMULATION AND EVALUATION OF SELF EMULSIFYING DRUG DELIVERY SYSTEM OF POORLY SOLUBLE DRUG USING VARYING CHAIN SURFACTANTS
Authors: CHOUHAN SHAILENDRA , CHAUHAN L. S.
Published: June 2022

In the present study, the aim was to formulate self-emulsifying drug delivery system of mefenamic acid. Two homologous surfactants of Tween series, Tween 20 and Tween 40 were used as surfactants. The two surfactants were used to formulate a self-emulsifying system of mefenamic acid using a common co-surfactant ethanol. The clear microemulsion regions obtained in phase diagram of Tween 40 was larger than Tween 20; which indicates that Tween 40 has good emulsifying ability. Tween 20 has a hydrophobic chain length of 12 carbons, whereas Tween 40 has a hydrophobic chain length of 16 carbons, so increment in carbon chain length provides good self-emulsifying ability due to better shielding of the hydrophobic core. This inference is further consolidated after formulating six different formulations using the two surfactants and subjecting them to various evaluation parameters. The formulations containing Tween 40 were superior in all the evaluation parameters, including particle size, zeta potential, and drug release rate. The optimized formulation’s particle size, zeta potential, and drug release rate (in 60 minutes) were 187.20 nm, -22.2 mV, and 90.42%, respectively.
ANTIOXIDANT AND NEPHROPROTECTIVE ACTIVITY OF FLAVONOID RICH FRACTION OF ALPHONSEA SCLEROCARPA Thw
Authors: DOKUPARTHI SUDHEER KUMAR , REDDY T. RAMA MOHAN
Published: June 2022

The kidney is one of the crucial organs to maintain proper homeostasis in the body, and develop nephroprotective agents to retain kidney health and an absolute requisite. Since plant-based medicine gained importance due to fewer side effects and more safety, a herbal approach to develop nephroprotective agents is still necessary. Our present investigation is aimed to screen the antioxidant and nephroprotective activity of Alphonsea sclerocarpa leaves. Wistar rats were used in the current paracetamol-induced nephrotoxicity model through standard experimental procedures. N-acetyl cysteine (NAC) is taken as standard, the flavonoid-rich fraction of A. sclerocarpa was given to the animals in two doses (200 and 400 mg/kg body weight) for seven days. After the treatment, blood samples were collected from all the animals and sacrificed for histopathological studies. To support this investigation, phytochemical screening, total phenolic, flavonoid, tannin contents were also determined. The antioxidant activity studies by DPPH assay, NO free radical scavenging assay, and total antioxidant assay were also screened using standard protocols. Results unveil that the plant is rich in polyphenolic contents, and the flavonoid-rich fraction has statistically significant (P<0.001) nephroprotective activity in a dose-dependent manner compared to the standard N-acetyl cysteine. The biochemical and histological studies were also conducted in connection with the titled activity and found significant to improve the abnormal blood parameters and enzymatic and non-enzymatic antioxidants in the kidney tissue. To wrap up, all the biochemical, behavioral, and histological data declared that the flavonoid-rich fraction of A. sclerocarpa is more potent among all the extracts to protect against oxidative stress and subsequent improvement of the physiological parameters of the kidney. The antioxidant property of the phytochemicals present in the extract may be responsible for the affirmed activity.
RP-HPLC Method Development and Validation for Simultaneous Estimation of Clobetasol Propionate and Fusidic Acid in Cream
Authors: MOHAPATRA DEEPALI P. , Patel Alisha , Mohapatra Tapas K.
Published: June 2022

A simple, rapid, precise, and accurate high-performance liquid chromatography method was developed for simultaneous estimation of Clobetasol propionate and Fusidic acid in cream. The separation was obtained using a mobile phase consisting of Acetonitrile and Water in the ratio of 90:10 and adjusting pH 5.0 with Glacial acetic acid (10%) using Shim-pack solar C18 (250 × 4.6 mm, 5 μm) column. The flow rate of 1.0 mL/min and UV detection at 240 nm was employed. The retention time for Clobetasol propionate and Fusidic acid was 4.787 min and 6.006 min respectively. Linearity for Clobetasol propionate and Fusidic acid was found to be in the range of 3-7 μg/mL and 120-280 μg/mL, respectively. The method was validated as per the ICH guidelines and the results were within the acceptance criteria for precision, linearity, specificity, and robustness.
Development and Optimization of Nefopam hydrochloride Push-Pull Osmotic Pumps by Design of Experiments
Authors: Gorasiya Prashant , Patel VIPUL
Published: June 2022

Nefopam hydrochloride (NFH) is one of the centrally acting NSAIDs drug used for pain management. The main objective of this research is to study the effect of ratio of Cellulose acetate: Polyethylene glycol (PEG) 3350 and % weight gain in extended release (ER) coating of push-pull osmotic pump (PPOP) tablets, optimized by design of experiment (DoE) using response surface face center (α=1), central composite design having two independent variables at three levels. PPOP tablets of NFH was administer once in a day to reduce dosing frequency and improve patient compliance. PPOP tablets contains drug layer and push layer, compressed in to bilayer tablets which is further coated with cellulose acetate (CA) as semipermeable membrane polymer and PEG 3350 as a plasticizer or pore forming agent. ER coated tablets mechanically drill ~0.50mm on drug layer part for the controlled release of drug up to 24 hrs. Based on the results it can be concluded that the ratio of CA: PEG 3350 and % weight gain in ER coating of PPOP tablets shows significant impact on % drug release. At lower % of PEG, burst release was observed due to cracking of ER coating layer, while at higher % of PEG, slightly rapid release of drug was observed. % Drug release is decrease with increase in the % weight gain of tablets.  PPOP Tablets with 10% of PEG 3350 (Ratio of CA:PEG 3350, 90:10) and 8% weight gain exhibits zero order kinetic drug release up to 24 hrs.
Febuxostat Loaded Microballoons: A Novel Approach for Gastric Retention
Authors: Gupta Mohanlal , Varia Umang , Katariya Hitesh , Detholia Krunal
Published: June 2022

Febuxostat loaded microballoons (FEB-MBs) were formulated using a non-aqueous solvent evaporation method using Eudragit RS 100, HPMC K4 M as a polymer, and span 80 as a surfactant. The ratio of solvents like methanol and dichloromethane, liquid paraffin as a processing medium. The formulation was optimized by the Box-Behnken design. Optimized formulation was evaluated for particle size, entrapment efficiency, % buoyancy, Percentage yield, in-vitro release studies, and stability study. Mean particle size 80.11 ± 0.349, entrapment efficient 83.25 ± 0.526, and % buoyancy 92.41 ± 0.57 were found for optimized formulation. Scanning electron microscopy (SEM) image of formulation shows discrete particle size with smooth surface texture with a hollow space and spherical shape and particle size < 200 μm. The result of in-vitro study shows an improved rate of drug release for a longer period from FEB-MBs compared with pure drugs. This is due to increases in the surface area leads to increases in absorption. The stability study shows no significant change in microballoons of the optimized formulation after 30 days of storage as per ICH guidelines. This multi particulate system provides an excellent approach for sustained release of a medicament for longer, thereby reducing dose frequency.
Assessment of Hepatoprotective Activity of Hyptis capitata Jacq. Against Oxidative Stress Induced by H2O2
Authors: V. Sumitha  , Mini I. , Nair Laija. S.
Published: June 2022

Medicinal plants occupy a key position in maintaining the health of the human population. Hyptis capitata Jacq. is an exotic ethnomedicinal plant of Lamiaceae possessing immense potential. The present study was carried out to assess the in vitro hepatoprotective activity of methanolic leaf extract of H. capitata against H2O2 induced oxidative stress in HepG2 cell lines. Total antioxidant capacity and Superoxide radical scavenging activity of the extract were also performed. The extract displayed considerable free radical scavenging activity (P < 0.01). MTT assay was used to assess the in vitro hepatoprotective activity in HepG2 cell lines. The extract displayed concentration-dependent cell viability with maximum protection (63.97 ± 1.23%) in H2O2 induced HepG2 cell lines at 100 μgml-1. H. capitata is a promising herb with significant antioxidant and hepatoprotective potential.
TOTAL PHENOLIC, FLAVONOID CONTENT, AND ANTIOXIDANT ACTIVITY OF JUSTICIA TRANQUEBARIENSIS L.F. AND CYCAS BEDDOMEI DYER. LEAVES
Authors: Hari Veluru. , Jothieswari Dhamotharan. , Maheswaramma Kalluru. Sesha
Published: June 2022

Polyphenolics such as tannins and flavonoids are proved as powerful antioxidants to resolve cellular stress, sustain homeostasis in the body and prevent stress-associated disorders. Plant-based medicine gained importance due to its safety margin and multiple benefits. Regular intake of antioxidants is an alternative to avoid serious illness. The current investigation is aimed to measure the phenolic, flavonoid content, the antioxidant activity of Justicia tranquebariensis L.f. and Cycas beddomei leaves. The selected plants are used by tribes and traditional medicine to cure various diseases. Total phenolic content was estimated using the Folin–Ciocalteu colorimetric method, taking gallic acid as standard. At the same time, total flavonoid content was determined by aluminum chloride colorimetric assay using Rutin as standard. The absorbance was measured at 760 nm and 510 nm, respectively. Antioxidant activity was measured by two In vitro methods (DPPH and NO free radical scavenging assay) using standard protocols, where Ascorbic acid served as a reference standard. Results disclosed that the total phenolic content for the methanolic extracts of C. beddomei (36.14 ± 1.72) and J. tranquebariensis (28.57 ± 0.91) was found to be higher than petroleum ether extracts. Similarly, C. beddomei (28.13 ± 2.48) is richer in flavonoids than J tranquebariensis (20.32 ± 1.24). In DPPH assay, methanolic extract C. beddomei (78.21%) is more effective to inhibit the free radicals than J. tranquebariensis (73.05%) with IC50 values 41.55μg/ml & 59.52 μg/ml respectively at higher doses that are comparable to standard ascorbic acid (84.34%, IC50 =63.27 μg/ml). Similarly, in NO free radical scavenging assay, methanolic extract of C. beddomei (72.54%) stood best among all to scavenge the free radicals with IC50 values 50.06 μg/ml, whereas ascorbic acid is found to inhibit 83.26% with IC50 values 39.75μg/ml. The presence of various secondary metabolites such as alkaloids, carbohydrates, phenols, steroids, terpenoids, glycosides, saponins, especially tannins and flavonoids, either alone or in combination, may be responsible for the observed scavenging property. The quantity of the phenolic compounds and flavonoids can be directly correlated to the exhibited activity.
Enantioselective RP-UFLC Method for the Simultaneous Estimation of Sitagliptin (STG) enantiomers (R and S) in racemic mixture and their Pharmacokinetic assessment in male Wistar Rats
Authors: Srinivas Chintha , Qureshi Husna Kanwal , Shyam Panga , Veeresham Ciddi
Published: June 2022

The present work aims to develop and validate a simple, rapid, and reproducible reverse phase ultra-fast liquid chromatography method with a UV detector (RP-UFLC-UV) was developed for the separation and determination of sitagliptin (STG) enantiomers (S-(STG) and R-(STG)) simultaneously. Baseline separation was achieved on Lux cellulose-1 column, (cellulose tri-(3,5-dimethyl phenyl carbamate (Chiralcel OD-RH, 250 mm × 4.6 mm, 5 μm) column and mobile phase consisted of 20mM borate buffer solution (pH = 9±0.05) and ACN in the ratio of (60:40, v/v) at a flow rate of 0.8 mL/min was used. Detection of peaks was monitored at 262 nm. For analyzing the STG enantiomers in the rat serum and pure API, a method was developed using the chiral RP-UFLC-UV method was validated. The single oral dose of 2.5 mg/kg of STG racemate was administered to a group of 6 healthy rats for a comparative pharmacokinetic study of both the enantiomers. The linear range of the calibration curve for each enantiomer was 0.5–64 μg/mL. The precision of this method at concentrations between 0.5–48 μg/mL was within 8.65% and the % recovery (accuracy) of both sitagliptin (STG) enantiomers (S-(STG) and R-(STG) were 98.47–101.02% and 98.93-100.52%. The precision at LLOQ (0.5 μg/mL) was between 8.65%-7.09%, which was poor than that at QC levels, and the average extraction recovery was higher than 85% for both sitagliptin (SGT) enantiomers at QC levels, and its pharmacokinetics of enantiomers was found to be stereoselective.
A validated LC-MS/MS method for pharmacokinetic study of edoxaban in healthy rabbits
Authors: Vasanth D. Atul , Rajkamal B.
Published: June 2022

A liquid chromatography-tandem mass spectrophotometric (LC–MS/MS) method was developed to quantify Edoxaban in rabbit plasma employing liquid liquid extraction with ethyl acetate. Developed method was validated for specificity, precision, accuracy, recovery, and stability characteristics. Chromatographic separation was achieved on Chromolith C18column (100 mm x 4.6 mm x 5 μm) with 70:30 ratio of methanol and 0.1% formic acid as an isocratic mobile phase with a flow rate of 0.80 mL/min. The developed LC-MS method was applied to assess pharmacokinetics parameters of edoxaban in healthy rabbits. Six Male albino rabbits weighing 2.0-2.5 Kg were randomly selected for the pharmacokinetic study. Blood samples (1-mL) were withdrawn from the marginal ear vein from 0 to 24 hours after administration (1.2 mg/kg). Plasma was separated by centrifugation and the plasma concentrations of edoxaban at various times were determined by LC-MS/MS. Pharmacokinetic parameters was calculated. Edoxaban showed Tmax of 2.0 and mean Cmax, AUC0®t and AUC0®a for Test formulation is 213.83 ± 10.46, 945.13 ± 24.32 and 986.135 ± 19.31, respectively. A highly specific, rugged, and rapid method with sufficiently low LLOQ was developed to analyze routine samples of single dose or multiple-dose pharmacokinetics with any marketing formulation of edoxaban.
Quality by Design Enabled Development and Optimization of the Nanoparticulate System of Cabazitaxel
Authors: Paithankar Mahesh , Bhalekar Mangesh
Published: June 2022

Cabazitaxel (CTX), a novel taxane derivative, has proven effective in many solid tumors. It is also approved in many countries for multiple uses in solid tumors. The current marketed formulation lacks the tumor-targeting ability, and its uneven distribution in the body causes toxicity to normal tissues. Further, it is a surfactant (polysorbate 80) based micellar formulation composed of ethanol as a co-solvent to improve the solubility of CTX, which causes severe and life-threatening side effects. Hence, to avoid the problem associated with this conventional CTX formulation, the nanoparticulate drug delivery system of CTX was developed by employing the Quality by Design (QbD) approach. The CTX nanoparticulate system was developed by employing a bottom-up followed by a top-down approach. The size reduction was obtained by High-Pressure Homogenizer (HPH). The formulation optimization was done using QbD approach. Design of experiments (DoE) was used to understand the effect of various formulation and process variables on a dependent variable like particle size distribution.The stabilizer concentration, concentration of solubilizer, HPH pressure, and passes were selected as independent factors while particle size distribution was selected as a dependent factor for evaluation. The nanoparticulate system was developed using PEG-400 as solubilizing agents, while Soya Phosphatidylcholine (SPC) was used as a surface stabilizer. Response surface plots revealed a decrease in particle size with increasing concentration of SPC and PEG 400. Similarly, a decrease in particle size with increased HPH passes and pressure was found. The optimum concentrations of SPC and PEG 400 were found to be 20% and 2.5%, respectively. 20 KPSI pressure and 5 HPH passes were derived as optimized processing parameters from DoE. The optimized formulation had a size of 43.5 nm, with PDI < 0.4. Due to its narrow particle size distribution, the formulation did not show any increase in particle size or aggregation up to 24 hours. The present research confirms the feasibility of developing the nanoparticulate system of CTX using the bottom-up followed by the top-down technique. The formulation was systematically optimized using QbD approach. The optimum concentration of PEG 400 as solubilizer and concentration of SPC as stabilizer was obtained from DoE, yielding optimum particle size and stability.
Potency of Phytocompounds as Hydroxychavicol and Plumbagin in Combination to Fight Against Leukemia via Activation of MAPK-Mediated Apoptotic Pathway: An In vitro Approach
Authors: Manna Anirban , Roy Tapasi , Das Tanusree , Bandyopadhyay Santu , Swarnakar Snehasikta
Published: June 2022

Plants provide natural molecules as an effective agent for phytomedicine. Anticancer properties of natural products are well described. Several studies on hydroxychavicol (HCH), and plumbagin (PLB), which are found in Piper betle leaf and Plumbago sp. respectively, are evidenced as anti-carcinogenic effect on chronic myeloid leukemic (CML) cells through increased reactive oxygen species (ROS). An attempt was taken to determine the efficacy of a new combination of HCH and PLB on CML cells (K562) and the mechanism of apoptosis thereon. 3-{4,5-Dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the dose for individual and combination treatments of HCH and PLB against leukemic cells, (K562). Apoptotic activity was assessed through flow cytometric analysis with annexin V-FITC/propidium iodide staining. Immunoblots were also performed on cell extracts before and after the treatments. Levels of ROS and nitric oxide (NO) in K562 cells were measured by DCF-DA and DAF-FM staining, respectively. In addition, P38 and JNK siRNA transfection were performed to assess the roles of mitogen-activated protein kinase (MAPK) pathways on apoptosis. Combination treatments of HCH (16 μM) and PLB (0.5 μM) showed synergistic effects on reducing viability and increased cellular apoptosis of K562 cells. Combined treatments showed elevated reactive oxygen species (ROS) and NO levels than individual treatments of HCH and PLB. Moreover, decreasing the ROS generations by antioxidants/catalase reversed cell deaths and increased viability. Immunoblotting of MAPK pathways components showed reduction of pERK levels, while upregulation pJNK and pP38 levels upon HCH+PLB treatments. Furthermore, silencing of JNK and/or P38 rescued the K562 cells from deaths. The present study indicates combination treatments of HCH and PLB act as a better therapeutic against CML by promoting MAPK-mediated apoptosis via increased oxidative and nitrosative stress. This in vitro approach is the first report describing the mechanism of action of HCH/PLB to fight against Leukemia via interaction with phosphorylated P38.
INFLUENCE OF PARTICLE SIZE AND PARTICLE DEPOSITION OF INHALED MEDICATION IN LUNG DISEASE: A COMREHENSIVE REVIEW
Authors: Dudhat Kiran R. , Patel Harsha V.
Published: June 2022

Drug particles less than 5 μm have the greatest probability of deposition in the lung, whereas those less than 2 μm tend to be concentrated in the alveoli. A large proportion of particles within the 2-5 μm range are present in the dose released from the inhaled drug, providing a relatively even distribution across the lungs. The efficient need for inhaled therapy highly depends on the essence of the method of drug delivery and the patient's ability to correctly use the system. A large range of inhaler products, each with positive and negative aspects, are on the market. It facilitates the administration of a lower dose; there is a quicker onset of action and less severe side effects. The deposition of the inhaled drug in the lung is dependent on particle size, inhalation technique and the type of inhaler device. Importance of particle size distribution and Particle aerodynamic diameter, Influence of environmental humidity on particle size Particle deposition in the airways, Methods to identify drug deposition in lungs, Physiological factors which affect the therapeutic efficacy of pulmonary delivery drugs. The nano and micro size particles is a mainstay of treatment for a variety of pulmonary diseases because they provide a platform to deliver drugs directly reliably and inexpensively to the disease site, thus allowing for a minimum amount of drug to be used and minimize side effects.
A Study on Preclinical Safety and Efficacy of MCP I Conjugated Gold Nanoparticles based oral contraceptive using Biomarkers of Reproductive Tissues and Blood Serum of Male Albino Wistar Rats
Authors: MOHAMMAD IRSHAD
Published: June 2022

Characterized MCP I fraction of Carica papaya seeds is being considered a potential contraceptive agent. Utilization of gold nanoparticles as a carrier molecule enhanced its targeted bioavailability, biocompatibility, in vitro stability against blood serum and pH gradient. In this study, preclinical safety and efficacy were assessed employing concerned biomarkers of blood serum and excised reproductive tissues for further approval of this nanoformulation. Experimental groups A, B & C were consists of vehicle control, orally treated with MCP I (50 mg/kg body wt./day) and MCP I conjugated gold nanoparticle (200µg/kg body wt./day) containing nine male albino Wistar rats in each. Three animals were sacrificed monthly interval during 90 days of investigation period. No significant differences were examined in markers of blood serum i.e., cholesterol, creatinine, lactate dehydrogenase, creatine kinase, bilrubin, urea, triglyceride, HDL and concentrations of testosterone, luteinizing hormone and follicle stimulating hormone except drastic reduction in SGOT (p< 0.001) and SGPT (p< 0.05; p< 0.01; p< 0.001) in group C. The glycogen, cholesterol and lactate dehydrogenase level in testicular tissues, sialic acid and fructose corresponded to epididymal and seminal vesicles, respectively, demonstrated insignificant changes. Significant diminution was recorded in the level of L-carnitine and α-glucosidase at 60 days in group B (p< 0.05) and 30 days in group C (p< 0.01; p< 0.001) of epididymal tissues. Prostatic acid phosphatase was increased (p< 0.05; p< 0.01) in group C. While antioxidant biomarkers in testicular tissues viz., lipid peroxidase, superoxide dismutase, reduced glutathione and catalase were revealed insignificant alteration. Thus, status of biomarkers indicate that synergistic effect of MCP I conjugated gold nanoparticle was found to be targeted, safe and effective for oral contraception in male albino rats at highly reduced dosage compared to pure MCP I treated animals which may open new avenues for clinical development.
Molecular Docking, Binding Energy and Molecular Dynamics Simulation Studies of Piperazin-1-ylpyridazine Derivatives as Deoxycytidine Triphosphate Pyrophosphatase Inhibitors
Authors: Mishra Shashank , Sharma C. S.
Published: June 2022

Cancer is a most serious health problem globally due to increased mortality. Deoxycytidine triphosphate pyrophosphatase (dCTPase) enzyme involved in cancer progression and cancer cell stemness and found over-expressed in breast cancer. This overexpression makes it of attractive target to discover new class of anticancer therapy. In the present work, we have selected piperazin-1-ylpyridazine derivatives as dCTPase inhibitors and performed molecular docking and dynamics simulations analysis to evaluate the binding pattern of selected compounds with target protein. Compound P21 has highest binding affinity towards dCTPase protein with -4.649 as Glide Gscore. In all compounds, only pyridazine and caboxamide nucleus involves in hydrogen bond formation and benzyl or phenyl nucleus involves in π-π stacking interaction. These observations provide the valuable lead for ligand based anticancer drug design.
A Stability indicating Reverse Phase High Performance Liquid Chromatography Method for simultaneous estimation of Allantoin, Hydroquinone and Tretenoin in Cream formulation
Authors: Shilu Raksha , Kapupara Pankaj
Published: June 2022

The present investigation deals with simple, sensitive, rapid, precise and accurate reverse phase high performance liquid chromatography (RP-HPLC) method developed and validated for simultaneous estimation of Hydroquinone, Allantoin and Tretenoin in a cream formulation. The chromatographic separation was achieved on a reversed-phase InertsilC18 (4.6mm I.D. × 250mm, 5μm) column using a mobile phase consisting of Buffer (pH 3.5) 0.05M Potassium dihydrogen ortho phosphate-Methanol (70:30% V/V) at a flow rate of 1-mL/min and UV detection at λmax 223 nm. The method showed linearity with correlation coefficient of Hydroquinone, Allantoin and Tretenoin was 0.999, 0.999 and 0.999 over the range of 100–300 μg/mL, 50 to 150 μg/mL and 0.625 to 1.875 μg/mL, respectively. The mean recoveries were found to be 99.00 to 101.00% for all the components. The method was validated as per the ICH guidelines. The developed protocol was most accurate, repeatable, and detectable towards hydroquinone, allantoin and tretenoin in combination without any unwanted interference. When evaluated on various parameters like system suitability, precision, accuracy, linearity, robustness, stablity study, the method is efficient in separating the API from its degradants and can be utilized for analyzing the samples of hydroquinone, allantoin and tretenoin.