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Reference Formulation (reference + formulation)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	25%

Selected Abstracts

Ticlopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry.

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004
Application to bioequivalence study
Abstract A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid,liquid extraction using diethyl ether,hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C8 4 µm analytical column (150 × 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0,1000 ng ml,1 (r2 > 0.999427). The limit of quantification was 1.0 ng ml,1. This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and area under the curve ratios were all inside the 80,125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Automated determination of venlafaxine in human plasma by on-line SPE-LC-MS/MS.

JOURNAL OF SEPARATION SCIENCE, JSS, Issue 4 2009
Application to a bioequivalence study
Abstract A new automated SPE-LC-ESI-MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction-monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25,200 ng/mL (r >0.997). The between-run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between-run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth-Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off-line liquid,liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6,103.4% for AUC0,48 h and 102.2,112.6% for Cmax. Since both 90% CI for AUC0,48 h and Cmax were included in the 80,125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption. [source]

Relative oral bioavailability of microgranulated amoxicillin in pigs

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002
P. Anfossi
A new microgranulated formulation of amoxicillin trihydrate for in-feed medication was developed using a lipogelled matrix. Its relative bioavailability was compared with powdered drug in pigs and an assessment was made to determine whether therapeutic concentrations were achieved. Microgranules containing 10% (MICR10) and 30% (MICR30) amoxicillin and free amoxicillin trihydrate powder (reference, AMX) were administered at dosages of 50 mg of amoxicillin/kg b.w. using a three-way-crossover design. Amoxicillin analysis in serum was performed by a sensitive high performance liquid chromatography (HPLC) method with fluorometric detection, using an extraction procedure already described for edible tissues of fish and adapted and validated for pig serum. The oral bioavailability of both microgranulated formulations was higher than that of the reference formulation [relative bioavailability (F): 153.9 ± 58.2% for MICR10; 126.2 ± 70.5% for MICR30] and the area under the concentration,time curve (AUC) values of MICR10 and AMX formulations were significantly different (P < 0.05). Differences between the mean maximum concentration (Cmax), time of Cmax (tmax) and mean residence time (MRT) of the drug formulations were not significant. Microgranulated amoxicillin is suitable for in-feed administration to pigs and, because of its higher oral bioavailability compared with the powdered compound, it may be more effective for the treatment of susceptible infections. [source]

Bioequivalence of four preparations of enrofloxacin in poultry

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001
L. H. Sumano
In various parts of the world, many 10% enrofloxacin commercial preparations for water medication of chicken are being employed. To avoid the development of bacterial resistance to this agent, the original trademark and similar preparations must be bioequivalent. To assess whether or not bioequivalence exists among the pioneer vs. three commercial preparations of enrofloxacin, a controlled pharmacokinetic study was conducted. The following variables were compared: maximal plasma concentration (Cpeak), time to Cpeak, bioavailability (expressed as the area under the concentration vs. time curve), elimination half-life, and the shapes of the respective time-serum concentrations of enrofloxacin profiles. Results indicate that all three similar commercial preparations had lower Cpeak values than the reference formulation, being 39.62 to 67.77% of the corresponding Cpeak reference. Additionally, bioavailability of enrofloxacin in the pioneer product was statistically higher (P < 0.05). Based upon these results, we conclude that although all preparations were formulated as water-soluble products, bioequivalence studies are mandatory for the analogue formulations to ensure product comparability. Lack of product bioequivalence could facilitate the development of bacterial resistance and limit the useful life span of the product. [source]

An effective strategy for the multibody simulation of jointed FE models in the framework of the floating frame of reference formulation.

PROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2008
Wolfgang Witteveen
In multibody systems (MBS), where elastic bodies are represented in the frame work of the ,floating frame of reference formulation' (FFRF), structural deformation is usually computed by the superposition of time invariant trial vectors (commonly called ,modes'). However, the mode bases, which are discussed in the literature, do not take joints into special account at the stage of mode generation. In the presented paper we propose a problem,oriented extension of classical mode bases in order to consider the presence of joints. In the novel extension which we call ,Joint Interface Modes' (JIMs), Newton's 3rd law across the joint is taken into account at the stage of mode generation, which leads to a superior convergence at the stage of mode based computation. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometry

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2001
M. Carvalho
Abstract Objective,To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine® 5 mg tablet from Merck S.A. Indústrias Químicas, Brazil as test formulation and Norvasc® 5 mg tablet from Laboratórios Pfizer Ltd., Brazil as reference formulation) in 24 healthy volunteers of both sexes. Methods,The study was conducted using an open, randomized two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 144 h period. Plasma amlodipine concentrations were analyzed by combined liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the amlodipine plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC0,inf and Cmax. The statistical interval proposed was 80,125% according to the US Food and Drug Administration Agency. Results,The limit of quantification was 0.1 ng/ml for plasma amlodipine analysis. The geometric mean and the 90% confidence interval (CI) test/reference ratios were 101.2 (92.9,110.2%) for AUClast, 99.6 (91.5,108.4%) for AUC0,inf and 98.5 (89.0,109.1%) for Cmax. Conclusion,Since the 90% CI for AUClast, AUC0,inf and Cmax ratios were within in the 80,125% interval proposed by the US FDA, it was concluded that Amlodipine® 5 mg tablet (test formulation) was bioequivalent to Norvasc® 5 mg tablet, in terms of both rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2001
Jörn Lötsch
Aims, To assess the pharmacokinetic equivalence of two different formulations of ibuprofen lysinate with special focus on the expected effects. Methods, Sixteen healthy volunteers received cross-over ibuprofen lysinate as either one tablet of 400 mg (,test') or two tablets of 200 mg (,reference'). Ibuprofen plasma concentrations were followed up for 10 h. Bioequivalence was assessed by standard noncompartmental methods. Ibuprofen plasma concentrations were fitted with a model that took bioinversion of R- to S-ibuprofen into account. Results, Peak plasma concentrations of R- and S-ibuprofen were 18.1 and 20 µg ml,1 (test), and 18.2 and 20 µg ml,1 (reference). Areas under the plasma concentration vs time curves were 39.7 and 67.5 µg ml,1 h (test), and 41.1 and 68.2 µg ml,1 h (reference). Clearance of R-ibuprofen was 5.2 (test) and 5 l h,1 (reference). A specific plasma concentration was reached with the test formulation about 5 min later than with the reference. Parameters from compartmental modelling were (given for R-and then for S-ibuprofen): body clearance: 4.9 and 4.64 l h,1, central volume of distribution: 2.8 and 4.1 l, intercompartment clearance: 5.1 and 5.45 l h,1, peripheral volume of distribution: 4.1 and 5.2 l. The absorption rate constant was 1.52 h,1, and the test but not the reference formulation had a lag time of 0.1 h. Simulations showed similarity between formulations of the expected effects except for a calculated delay of 6 min with the test formulation. Conclusions, Ibuprofen formulations were bioequivalent. The pharmacokinetic model may serve as a basis for future pharmacokinetic/pharmacodynamic calculations after administration of racemic ibuprofen. [source]