scholarly journals In-vivo studies of metformin modified release formulations

2020 ◽  
Vol 11 (1) ◽  
pp. 115-119
Author(s):  
Nagarajan Janaki Sankarachari Krishnan ◽  
Elango Kannan
Keyword(s):  
High Sensitivity ◽  
Sample Volume ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Metformin Hydrochloride ◽  
Modified Release ◽  
Reverse Mode ◽  
Test Formulation ◽  
Us Fda

The current study was undertaken to conduct In vivo studies and to establish the new validated bioanalysis for the determination of Metformin present in Blood Plasma by using the Reverse Mode-LC Method. The separation of the Metformin was carried out on Reverse mode LC using Shimadzu® LC - 10AT with the following Stationary Phase: Kromasil octadecyl silane column (25 cm x 4.6 mm i.d., 5µm) Eluent: Cyanomethane: 25 mM Pentane Sulfonic acid of pH 3.5. ratio 09:91 % v/v with 1.0 ml/min flow rate has been fixed, and this has been measured at 232 nm, and the sample volume will be 10 ul using Rheodyne 7725i injector. Based on the method established for Metformin, the drug peak is well resolved at 11.11 min and validated as per US FDA guidelines with respect to linearity, accuracy, precision, robustness ruggedness, and stability. The calibration curve was found to be linear over a range of 0.025 –1 μg/mL (r2  = 0.9999). The method has proved high sensitivity and specificity. Established method have been used to quantify the Pharmacokinetic parameters like Cmax, Tmax, AUC0-t & AUC0-∞, Keli, and t1/2 studied and the values for reference formulation (660.05±91.52 ng/ml, 4.46 ±1.10  h, 8280.41 ± 1356.39 ng.h/ml, 9200.31± 1569.26 ng.h/ml, 0.11±0.03 h-1, and 6.96±1.53  h respectively) and the test formulation (   705.06±102.58  ng/ml, 4.13±0.74 h, 8185.21±2101.56 ng.h/ml, 8946.39± 2457.66 ng.h/ml, 0.12±0.03 h-1, and 6.06±1.61  h, respectively) were compared and found to be biologically equivalent. Based on the Pharmacokinetic and statistical analysis Test formulation of Metformin Hydrochloride containing 500 mg Metformin Hydrochloride (modified release formulations) is biologically equivalent to that of the Reference.

scholarly journals Bioanalysis and in-vivo studies of clarithromycin modified release solid dosage formulations by liquid chromatography-mass spectroscopy

2020 ◽  
Vol 11 (1) ◽  
pp. 87-92
Author(s):  
Nagarajan Janaki Sankarachari Krishnan ◽  
Elango Kannan
Keyword(s):  
Biological Fluid ◽  
Internal Standard ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Modified Release ◽  
Reference Formulation ◽  
Release Formulation ◽  
Solid Dosage ◽  
Test Formulation

The current study was undertaken to develop the new bioanalytical method and validation for determining Clarithromycin by LC-MS Method and as well as to conduct in vivo studies. Princeton octadecyl silane column (10 cm x 4.6 mm id, 5µm) used as adsorbent and cyanomethane: 0.5 % Methanoic acid was treated as the eluent for the separation of the analyte from the biological fluid in an isocratic mode having the ratio 60:40 % v/v and 0.5 ml/min as flow rate, and injection volume was set as 20 µl. APCI and the mass detected of Clarithromycin and Azithromycin (act as internal standard) was detected at 748.45 and 749.70, respectively. Developed bioanalytical methods have been used to quantify the Pharmacokinetic parameters like Cmax, Tmax, AUC0-t & AUC0-∞, Keli, and t1/2 studied and the values for reference formulation (3.382µg/ml, 7.333 h, 114.429µg.h/ml, 131.435µg.h/ml, 0.031 h-1, and 23.397h respectively) and the test formulation (3.847 µg/ml, 7.417 h, 132.318 µg.h/ml, 151.388 µg.h/ml, 0.031 h-1, and 23.187 h, respectively) were compared and found to be bioequivalent. Based on our study, the test formulation of Clarithromycin modified-release formulation containing 500 mg of Clarithromycin is Bioequivalent to that of the reference.  Compare to our method (LC-MS) is simple, sensitive, precise as well as comparable with the reference formulation of the modified release product of clarithromycin 500 mg.

Cationic Diclofenac Lipid Nanoemulsion for Improved Oral Bioavailability: Preparation, Characterization and In Vivo Evaluation

2015 ◽  
Vol 8 (2) ◽  
pp. 2874-2880
Author(s):  
Kishan Veerabrahma ◽  
Swapna Madishetty ◽  
Muzammil Afzal Syed ◽  
Prabhakar Kandadi
Keyword(s):  
Oral Bioavailability ◽  
Physical Stability ◽  
Cationic Lipid ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Drug Content ◽  
Lipid Nanoemulsion

Cationic nanoemulsions were reported to have increased bioavailability. The aim of present study was to prepare a cationic lipid nanoemulsion of diclofenac acid (LNEs) for improved oral bioavailability to treat arthritic conditions. The LNEs of diclofenac acid were prepared by using soya bean oil, egg lecithin, cholesterol and stearylamine. Stearylamine was used as positive charge inducer. The LNEs were processed by homogenization and ultrasonication. The formulation composition was selected based on earlier reports. The LNEs were characterized for size and zeta potential. The physical stability of LNEs was studied using autoclaving, centrifugal, desorption (dilution effect) stresses and on storage. The total drug content and entrapment efficiency were determined using HPLC. During in vivo studies in Wistar rats, the pharmacokinetic parameters of LNEs were compared with a prepared diclofenac suspension in sodium CMC mucilage. The selected formulations, F1, F2 and F3, were relatively stable during centrifugal stress, dilution stress and on storage. The drug content was found to be 2.38 ± 1.70 mg/ml for F1, 2.30 ± 0.82 mg/ml for F2, and 2.45 ± 0.66 mg/ml for F3. The entrapment efficiencies were 97.83 ± 0.53%, 97.87 ± 1.22% and 98.25 ± 0.21% for F1, F2 and F3 respectively. The cumulative percentage drug release from F1, F2 and F3 showed more release in pH 6.8 phosphate buffer than in pH 1.2 HCl. During oral bioavailability studies, the LNEs showed higher serum concentrations than a suspension. The relative bioavailability of the LNE formulations F1, F2 and F3 were found to be 2.35, 2.94 and 6.28 times that of F4 suspension and were statistically significant. Of all, the cationic lipid nanoemulsion (F3) was superior in improving bioavailability, when compared with plain emulsion (F1) and cholesterol containing LNE (F2). The study helps in designing the cationic oral nanoemulsions to improve the oral bioavailability of diclofenac.

Preclinical studies conducted on nanozyme antioxidants: shortcomings and challenges based on US FDA regulations

Nanomedicine ◽  
2021 ◽  
Author(s):  
Milad Ghorbani ◽  
Zhila Izadi ◽  
Samira Jafari ◽  
Eudald Casals ◽  
Foroogh Rezaei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Clinical Studies ◽  
In Vivo Studies ◽  
Preclinical Studies ◽  
Future Studies ◽  
Clinical Stages ◽  
Us Fda ◽  
Considerable Body

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.

scholarly journals Comparative in vivo study of pure drug and fast dissolving tablets of Simvastatin

2019 ◽  
Vol 9 (4-A) ◽  
pp. 490-496
Author(s):  
M. Suresh Babu ◽  
T. E. Gopalakrishna Murthy
Keyword(s):  
Rate Constant ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Pure Drug

The objective of this study was to investigate differences in the pharmacokinetic patterns between pure drug and an optimized  formulation of fast dissolving tablets  of Simvastatin. The formulations were administered to 2 groups of white New Zealand rabbits (n=6) following cross over design pattern and the plasma levels were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each formulation. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels.  The highest mean Cmax value was observed for optimized fast dissolving tablets (68.33 ± 0.42ng/ml) compared to  pure drug (27.72 ± 0.31ng/ml). The mean time taken to peak plasma concentration for (Tmax) following administration of pure drug  was  11.53 ± 0.011hours, while it was 6.09 ± 0.072 hour following administration of selected optimized fast dissolving tablets.The elimination rate constant (Kel) for pure drug and optimized fast dissolving tablets were found to be 0.58 ± 0.012h-1and 0.53 ± 0.014 h-1 respectively.  The absorption rate constant (Ka) for pure drug and optimized fast dissolving tablets were found to be 1.68 ± 0.01h-1and 5.53 ± 0.02h-1 respectively. The AUC0-αvalues observed with optimized fast dissolving tablets686.1.±2.07 nghr/ml in compared to pure drug values 191 ± 1.43 nghr/ml. Thus, the results of pharmacokinetic studies indicated rapid and higher oral absorption of Simvastatin when administered as its fast dissolving tablets. Both Ka and AUC were markedly increased by fast dissolving tablets. Keywords: LC-MS/MS, Simvastatin, fast dissolving, In-vivo studies, pharmacokinetic parameters.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

FORMULATION, OPTIMIZATION AND EVALUATION OF MOXIFLOXACIN HYDROCHLORIDE GASTRO RETENTIVE TABLETS

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (01) ◽  
pp. 79-84
Author(s):  
Raghavendra K. Gunda ◽  
◽  
A. Vijayalakshmi ◽  
K. Masilamani ◽  
◽  
...  
Keyword(s):  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Wet Granulation ◽  
Statistical Parameters ◽  
Compression Technique ◽  
Ich Guidelines ◽  
Gastro Retentive

The objective of the current study was to develop gastro retentive formulation of moxifloxacin. HCl using various drug release modifiers and performing in vitro and in in vivo evaluations. Moxifloxacin is a novel synthetic fluoro quinolone antibacterial agent. Floating, muco adhesive tablets of moxifloxacin. HCl were prepared using variable amounts of HPMCK100M, Lannea coromandelica gum by direct compression technique and wet granulation technique, respectively. Formulations were developed, optimized and checked for pharmacopoeial tests. Results show that all the batches lie within the standard limits. Dissolution parameters of all formulations were sy=ubjected to kinetic fitting and various statistical parameters were determined. Formulation (FS5 ) containing 50 mg of HPMCK100M and 50 mg of LCG, is the best formulation showing similarity f2 =71.734, f1 = 4.271 with the marketed product (Avelox). It follows Higuchi's kinetics, non-fickian diffusion first order kinetics(n=0.717). In vivo studies were performed for the FS5 with 6 healthy rabbits and pharmacokinetic parameters were determined, compared with Avelox and it was found that FS5 produced similar results. Stability studies were performed for FS5 as per ICH guidelines. Results were found to be satisfactory. FS5 is expected to improve patient compliance by means of providing good clinical outcome

scholarly journals Computer-Aided Prediction and Identification of Phytochemicals as Potential Drug Candidates against MERS-CoV

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hafiza Salaha Mahrosh ◽  
Muhammad Tanveer ◽  
Rawaba Arif ◽  
Ghulam Mustafa
Keyword(s):  
Respiratory Infections ◽  
Catalytic Triad ◽  
World Health ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Potential Drug ◽  
Drug Candidates ◽  
Starting Point ◽  
Computer Aided

The Middle East respiratory syndrome coronavirus (MERS-CoV) is the major leading cause of respiratory infections listed as blueprint of diseases by the World Health Organization. It needs immediate research in the developing countries including Saudi Arabia, South Korea, and China. Still no vaccine has been developed against MERS-CoV; therefore, an effective strategy is required to overcome the devastating outcomes of MERS. Computer-aided drug design is the effective method to find out potency of natural phytochemicals as inhibitors of MERS-CoV. In the current study, the molecular docking approach was employed to target receptor binding of CoV. A total of 150 phytochemicals were docked as ligands in this study and found that some of the phytochemicals successfully inhibited the catalytic triad of MERS-CoV. The docking results brought novel scaffolds which showed strong ligand interactions with Arg178, Arg339, His311, His230, Lys146, and Arg139 residues of the viral domains. From the top ten ligands found in this study (i.e., rosavin, betaxanthin, quercetin, citromitin, pluviatilol, digitogenin, ichangin, methyl deacetylnomilinate, kobusinol A, and cyclocalamin) based on best S -score values, two phytochemicals (i.e., pluviatilol and kobusinol A) exhibited all drug-likeness properties following the pharmacokinetic parameters which are important for bioavailability of drug-like compounds, and hence, they can serve as potential drug candidates to stop the viral load. The study revealed that these phytochemicals would serve as strong potential inhibitors and a starting point for the development of vaccines and proteases against MERS-CoV. Further, in vivo studies are needed to confirm the efficacy of these potential drug candidates.

scholarly journals Preparation and in vivo Evaluation of Solid Dispersions Using Repaglinide

2018 ◽  
Vol 10 (05) ◽  
Author(s):  
D.V.R.N Bhikshapathi ◽  
I. Srinivas
Keyword(s):  
Solid Dispersion ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Parameters ◽  
Release Mechanism

In the present study, immediate release solid dispersion of Repaglinide was formulated by solvent evaporation technique. Repaglinide solid dispersions were prepared using PEG 8000, Pluronic F 127 and Gelucire 44/14 by solvent evaporation method. A 3-factor, 3-level central composite design employed to study the effect of each independent variable on dependent variables. FTIR studies revealed that no drug excipient interaction takes place. From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of Repaglinide has been converted into an amorphous form from crystalline within the solid dispersion formulation. The correlation coefficient showed that the release profile followed Higuchi model anomalous behavior and hence release mechanism was indicative of diffusion. From in vivo studies, the AUC0→24 h and peak plasma concentration (Cmax) was doubled when compared with pure drug. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The obtained results suggested that developed solid dispersion might be an efficacious approach for enhancing the solubility and bioavailability of Repaglinide.

scholarly journals In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

2012 ◽  
Vol 2012 ◽  
pp. 1-14
Author(s):  
Utpal Kumar Sanki ◽  
Badal Kumar Mandal
Keyword(s):  
Health Care Cost ◽  
Geometric Mean ◽  
Scale Up ◽  
Pharmacokinetic Parameters ◽  
Modified Release ◽  
Reference Formulation ◽  
Healthy Human ◽  
Serious Adverse Events

Alfuzosin, a selective alpha-1a antagonistis is the most recently approved AARAS, with limited cardiac toxicity and exclusively used for lower urinary tract syndromes (LUTS). In order to reduce pill burden and better patient compliance modified release (MR) formulations have been developed. Alfuzosin MR tablet was developed by the use of hot-melt granulation techniques using mono- and diglycerides as rate controlling membranes to minimize health care cost and uses of costly excipients. The other purpose of the study was to evaluate in vitro-in vivo performance of the scale up batch in healthy human subjects for commercialization. The blend uniformity (mean ± RSD%), assay, cumulative percent dissolution at 24 h, hardness, and friability of the biobatch were 100.2 ± 0.05%, 100.43 ± 0.023%, 93.98%, 4.5 kg, 5 min, and 0.08%, respectively. The in vivo pharmacokinetic parameters under fasting conditions between test and reference formulations (Uroxatral 10 mg extended release tablets) were comparable. The 90% CI, geometric mean ratio (%) and power of , AUCT, and AUCI of the fasting study for the test and reference formulation were 99.03% to 122.78%, 109%, 0.998; 92.94% to 116.71%, 104%, 1; 98.17% to 124.01%, 110% 1, respectively. The scale up biobatch showed negligible difference in in vitro properties with respect to the pilot batch. The formulation developed with these agents was safe to use as there were no serious adverse events developed during the conduction of the clinical trial on the healthy subjects. Furthermore, the developed formulation was bioequivalent with respect to rate and extends of absorption to the reference formulation.

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