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.

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 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.

Alternativas farmacéuticas: ¿pueden ser intercambiables?

2020 ◽  
Vol 2 (2) ◽  
pp. 38-42
Author(s):  
Miriam del Carmen Carrasco-Portugal ◽  
Francisco Javier Flores-Murrieta
Keyword(s):  
Generic Substitution ◽  
In Vivo Studies ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Reference Formulation ◽  
Active Moiety ◽  
Significant Difference ◽  
Pharmaceutical Form ◽  
Extent Of Absorption

Pharmaceutical alternatives are products with the same active moiety, but different salt, ester or pharmaceutical form. Regulatory agencies have different criteria for this kind of drug. The European Medicines Agency (EMA) accepts the generic substitution using these alternatives, whereas the Food and Drug Administration (FDA) only authorizes generic substitution of pharmaceutical equivalents. The objective of this paper is to describe some relevant aspects that should be considered before deciding on making a generic substitution with pharmaceutical alternatives. It is important to note that a pharmaceutical alternative must show no significant difference in the rate and extent of absorption (bioequivalence) in a well-conducted in vivo study when compared with the reference formulation. Current Mexican regulations state that generic substitution is possible using pharmaceutical alternatives when bioequivalence is demonstrated in in vivo studies conducted under the NOM-177-SSA1-2013 criteria. In conclusion, generic substitution with pharmaceutical alternatives is possible if these products demonstrate in vivo bioequivalence when compared with the reference product.

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.

scholarly journals Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

In vitro and in vivo Studies of a New Sustained Release Formulation of Morphine

2011 ◽  
Vol 58 (12) ◽  
pp. 647-652
Author(s):  
Amparo Araíco ◽  
Francisca Torres-Molina ◽  
Anas Saadeddin ◽  
Jaime Cárcel-Trullols ◽  
Josefa Alvarez-Fuentes ◽  
...  
Keyword(s):  
Sustained Release ◽  
In Vivo Studies ◽  
Release Formulation ◽  
Sustained Release Formulation

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.

scholarly journals Determination of myrislignan levels in BALB/c mouse plasma by LC-MS/MS and a comparison of its pharmacokinetics after oral and intraperitoneal administration

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jili Zhang ◽  
Hongfei Si ◽  
Jichao Sun ◽  
Kun Lv ◽  
Biqing Yan ◽  
...  
Keyword(s):  
Formic Acid ◽  
Intraperitoneal Administration ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Limit Of Quantification ◽  
Mouse Plasma ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Abstract Background Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. Results In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 μm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. Conclusions A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Pharmacokinetic Parameters ◽  
Reference Formulation ◽  
High Fat ◽  
Fasting Condition ◽  
Test Formulation ◽  
Healthy Chinese ◽  
Chinese Subjects ◽  
Fat Meal

Abstract Background: Levamlodipine, a calcium channel blocker, is used in treatment of hypertension. To compare the pharmacokinetic parameters between levamlodipine test formulation at a single dose of 5 mg and amlodipine reference formulation at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasting and high-fat meal group equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine levamlodipine in the plasma samples.Results: Within equivalence limits between 80 ~ 125%, the test formulation and the reference formulation were bioequivalent, with the 90% confidence intervals (CIs) for the ratio of geometric means of Cmax, AUC0-t, and AUC0-∞. The data were shown as Cmax (89.59% ~ 101.61%), AUC0-t (87.83% ~ 94.87%) and AUC0-∞ (86.28% ~ 93.49%) under fasting condition, Cmax (90.93% ~ 102.37%), AUC0–t (95.75% ~ 104.93%) and AUC0–∞ (95.36% ~ 105.33%) under high-fat meal condition. Serious adverse event was not observed.Conclusions: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasting condition and high-fat meal condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

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.

Sign in / Sign up

Export Citation Format

Share Document