Simulation of oral absorption from non-bioequivalent dosage forms of the salt of raltegravir, a poorly soluble acidic drug, using a physiologically based biopharmaceutical modeling (PBBM) approach

Magainin Pharmaceuticals Inc. – Biopharmaceutical Research  > Antibodies, Assay Kits, Biology Cells, cDNA, Clia Kits, Culture Cells, Devices, DNA, DNA Templates, DNA Testing, Elisa Kits, Enzymes, Equipments, Exosomes, Gels, Medium & Serums, NATtrol, Particles, Pcr Kits, Peptides, Reagents, Recombinant Proteins, Ria Kits, RNA, Vector & Virus, Western Blot >  Simulation of oral absorption from non-bioequivalent dosage forms of the salt of raltegravir, a poorly soluble acidic drug, using a physiologically based biopharmaceutical modeling (PBBM) approach
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Simulation of oral absorption from non-bioequivalent dosage forms of the salt of raltegravir, a poorly soluble acidic drug, using a physiologically based biopharmaceutical modeling (PBBM) approach

Non-bioequivalent plasma focus profiles amongst totally different dosage types of the salt of raltegravir, a poorly soluble acidic drug, had been investigated utilizing biorelevant in vitro testing mixed with the business in silico software program, Simcyp®. A suspension and a pill dosage types of raltegravir potassium had been chosen because the take a look at formulations. Whereas dissolution from the suspension was fast, dissolution from the tablets was gradual and delayed by pre-exposure to an acidic surroundings.

Moreover, it was assumed that gastric emptying of the tablets could be decided by the gastric motility sample as a result of the formulation is giant and didn’t disintegrate underneath biorelevant dissolution take a look at situations. With the intention to simulate in vivo dissolution and plasma focus profiles of the tablets, in vitro and in silico trials had been carried out contemplating the gastric emptying time as a key physiological issue. The impact of pre-exposure to acid within the abdomen on dissolution conduct within the gut was estimated by two-stage in vitro dissolution testing. Primarily based on these outcomes, theoretical in vivo dissolution profiles had been generated for various gastric emptying occasions.

Plasma focus profiles for every gastric emptying time had been simulated by inputting the theoretical in vivo dissolution profiles into the in silico mannequin constructed with the scientific knowledge of the suspension. Imply plasma focus profiles of the goal topic group had been calculated, taking the distribution of particular person gastric emptying occasions into consideration. Though the pill was anticipated to have complicated in vivo dissolution conduct, plasma focus profiles had been efficiently simulated by two-stage in vitro dissolution testing and the commercially out there in silico software program when gastric emptying was taken into consideration as the important thing physiological issue. The in vitro and in silico methodology introduced on this report could be a sensible method to simulate oral absorption from numerous formulations of poorly soluble weak acids and their salts.

 

Institution of fast-growing serum-free immortalised cells from Chinese language hamster lung tissues for biopharmaceutical manufacturing

Chinese language hamster (Cricetulus griseus) ovary-derived Chinese language hamster ovary (CHO) cells are essentially the most generally used mammalian hosts for the commercial manufacturing of recombinant therapeutics due to their capability to fold, assemble, and carry out post-translational modifications, akin to glycosylation, on proteins.
They’re additionally precious for his or her capability to develop in serum-free suspension cultures. On this research, we established a cell line derived from lung tissue of Chinese language hamsters, named Chinese language hamster lung (CHL)-YN cells. The biosafety of CHL-YN cells was confirmed by in vitro sterility testing, mycoplasma detection, and reverse transcriptase assays. One of many key traits of CHL-YN cells was their doubling time of 8.1 h in chemically outlined tradition medium; thus, they proliferate a lot sooner than standard CHO cells and basic mammalian cells.
Transgenes may very well be launched into CHL-YN cells with excessive effectivity. Lastly, between 50% to > 100% of the quantity of glycosylated immunoglobulin G (IgG)1 produced by CHO-K1 cells was produced by CHL-YN cells over a shorter time frame. In abstract, fast-growing CHL-YN cells are a novel cell line for producing recombinant proteins.
 Simulation of oral absorption from non-bioequivalent dosage forms of the salt of raltegravir, a poorly soluble acidic drug, using a physiologically based biopharmaceutical modeling (PBBM) approach
Simulation of oral absorption from non-bioequivalent dosage forms of the salt of raltegravir, a poorly soluble acidic drug, using a physiologically based biopharmaceutical modeling (PBBM) approach

Mannequin-Knowledgeable Drug Discovery and Improvement in Pulmonary Supply: Biopharmaceutical Pharmacometric Modeling for Formulation Analysis of Pulmonary Suspensions

For respiratory situations, focused drug supply to the lungs may produce increased native concentrations with diminished danger of antagonistic occasions in comparison with systemic administration. Regardless of the rising curiosity in pulmonary supply, the pharmacokinetics (PK) of medication following pulmonary administration stays to be elucidated. On this context, the applying of modeling and simulation methodologies to characterize PK properties of compounds following pulmonary administration stays a shortage.
Pseudomonas aeruginosa (PA) lung infections are proof against most of the present antibiotic therapies. Focused remedies for pulmonary supply may very well be notably useful for these native situations. On this research, we report the applying of biopharmaceutical pharmacometrics (BPMX) for the evaluation of PK knowledge from three investigational antimicrobial brokers following pulmonary administration of a suspension formulation. The noticed drug concentration-time profiles in lungs and plasma of the compound collection had been mixed for simultaneous evaluation and modeling. The developed mannequin describes the PK knowledge, bearing in mind formulation properties, and gives a mechanism to foretell dissolved drug concentrations within the lungs out there for exercise. The mannequin was then used to guage formulation results and the influence of variability on complete and dissolved drug concentrations in lungs and plasma.

96-Well Plate Plasmid DNA Miniprep Kit

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EUR 300.37

96-Well Plate Plasmid DNA Miniprep Kit

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Ultra-Fast 96-Well Plate Plasmid DNA Miniprep Kit

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Ultra-Fast 96-Well Plate Plasmid DNA Miniprep Kit

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96-well Genomic DNA Extraction Kit (1 plates)

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96-well Genomic DNA Extraction Kit (2 plates)

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96-well Genomic DNA Extraction Kit (4 plates)

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96-well Plant Genomic DNA Extraction Kit (1 plates)

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96-well Plant Genomic DNA Extraction Kit (2 plates)

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96-well Plant Genomic DNA Extraction Kit (4 plates)

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96-Well Plate Plasmid DNA Mini-Preps Kit (Vacuum Based)

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96-Well Plate Plasmid DNA Mini-Preps Kit (Vacuum Based)

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96-well Viral RNA/DNA Extraction Kit (1 plates)

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EUR 232.8

96-well Viral RNA/DNA Extraction Kit (2 plates)

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96-well Viral RNA/DNA Extraction Kit (4 plates)

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96-well Plasmid ezFilter Mini Kit

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EUR 444

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Plasmid DNA Extraction Mini Kit (100prep)

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EUR 168

Plasmid DNA Extraction Mini Kit (300prep)

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EUR 241.2

Plasmid DNA Extraction Mini Kit (100prep)

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EUR 154.8

Plasmid DNA Extraction Mini Kit (300prep)

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EUR 206.4

Genorise® Plasmid DNA Extraction Kit 1000

GR101073 1000
EUR 850

Genorise® Plasmid DNA Extraction Kit 100

GR101073-100 100
EUR 144

Genorise® Plasmid DNA Extraction Kit 200

GR101073-200 200
EUR 258

Genorise® Plasmid DNA Extraction Kit 500

GR101073-500 500
EUR 480

Plasmid DNA extraction and purification kit

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EUR 444

Genorise® Plasmid DNA Extraction Kit 50

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EUR 87

Plasmid DNA Extraction Kit (Rnase A included)

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Plasmid DNA Extraction Kit (Rnase A included)

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EUR 156

Plasmid DNA Extraction Kit (Rnase A included)

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EUR 226.8

Plasmid DNA Extraction Kit (Rnase A included)

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EUR 112.8

Plasmid DNA Extraction Mini Kit (300prep)-capless

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EUR 206.4

Plasmid DNA Extraction and Purification

EP10014 100 Tests
EUR 403.2

Plasmid DNA Extraction Midi Kit (25prep), Ion Exchange

FAPDE-002 25 preps
EUR 259.2

Plasmid DNA Extraction Midi Kit (50prep), Ion Exchange

FAPDE-002-1 50 preps
EUR 380.4

Plasmid DNA Extraction Maxi Kit (10prep), Ion Exchange

FAPDE-003 10 preps
EUR 241.2

Plasmid DNA Extraction Maxi Kit (20prep), Ion Exchange

FAPDE-003-1 20 preps
EUR 337.2

Plasmid DNA Extraction Mini Kit (Automatic Machine) Sample

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EUR 168

Miniprep Kit For Plasmid DNA Extraction And Purification

MB1005-100Reactions 100 Reactions
EUR 171.6

Miniprep Kit For Plasmid DNA Extraction And Purification

MB1005-250Reactions 250 Reactions
EUR 310.8

Miniprep Kit For Plasmid DNA Extraction And Purification

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Plasmid DNA ExtractionMaxi Kit (10prep), EndoToxinFree, Ion Exchange

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EUR 259.2

Plasmid DNA Extraction Maxi Kit (4prep), FavorFilter, Ion Exchange

FAFTE-001 4 preps
EUR 180

Plasmid DNA Extraction Maxi Kit (10prep), FavorFilter, Ion Exchange

FAFTE-001-1 10 preps
EUR 249.6

Plasmid DNA Extraction Midi Kit (25prep), FavorFilter, Ion Exchange

FAFTE-002 25 preps
EUR 294

Plasmid DNA Extraction Midi Kit (50prep), FavorFilter, Ion Exchange

FAFTE-002-1 50 preps
EUR 441.6

Plasmid DNA Extraction Midi Kit (25prep), EndoToxinFree, Ion Exchange

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EUR 276

Plasmid DNA Extraction Maxi Kit (4prep), FavorFilter, EndotoxinFree, Ion Exchange

FAFTE-001-EF 4 preps
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Plasmid DNA Extraction Maxi Kit (10prep), FavorFilter, EndotoxinFree, Ion Exchange

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EUR 259.2

96-Well Plate Viral DNA Miniprep Kit

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EUR 495.86

96-Well Plate DNA Cleanup Miniprep Kit

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96-well Viral DNA/RNA Kit

K1417-1 each
EUR 470.4

96-well Viral DNA/RNA Kit

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EUR 1227.6

96-Well Plate Plant Genomic DNA Miniprep Kit

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96 Well Plate Blood Genomic DNA Miniprep Kit

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96 Well Plate Blood Genomic DNA Miniprep Kit

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EUR 234.6

96-Well Plate Animal Genomic DNA Miniprep Kit

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96 well DNA plate with membrane (960ul each well)

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EUR 291.24

96-Well Plate Bacteria Genomic DNA Miniprep Kit

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96-well DNA–binding plates (black)

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Description: This product includes 4 Black 96-well plate for DNA binding and fluorescence detection

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Description: DNA Extraction Kit in Wells by Cygnus Technologies is available in Europe via Gentaur.

EpiMag 96-Well Viral RNA Extraction Kit (High Throughput)

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96-well DNA–binding Plates (Transparent)

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Description: This product includes 4 Transparent 96-well plate for DNA binding and light absorbance detection

96 Well Lung Tumor Genomic DNA Plate

D8235152-1 1 plate
EUR 328

96 Well Colon Tumor Genomic DNA Plate

D8235090-1 1 plate
EUR 328

96 Well Breast Tumor Genomic DNA Plate

D8235086-1 1 plate
EUR 328

96 Well Stomach Tumor Genomic DNA Plate

D8235248-1 1 plate
EUR 328

Genorise® Plasma/Serum DNA Extraction Kit 1000

GR101010 1000
EUR 1045

Genorise® Plasma/Serum DNA Extraction Kit 500

GR101029 500
EUR 480

Genorise® Plasma/Serum DNA Extraction Kit 200

GR101030 200
EUR 258

Genorise® Plasma/Serum DNA Extraction Kit 100

GR101031 100
EUR 144

DNA Extraction Buffer for wells

D105 30 ml
EUR 244.8
Description: DNA Extraction Buffer for wells by Cygnus Technologies is available in Europe via Gentaur.

Genorise® Plasma/Serum DNA Extraction Kit 50

GR101032 50
EUR 87

Genorise® Plasma/Serum Viral DNA Extraction Kit 1000

GR101012 1000
EUR 1045

Genorise® Plasma/Serum Viral DNA Extraction Kit 500

GR101033 500
EUR 480

Genorise® Plasma/Serum Viral DNA Extraction Kit 200

GR101034 200
EUR 258

Genorise® Plasma/Serum Viral DNA Extraction Kit 100

GR101035 100
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96-Well Plate

1996-2 each
EUR 124.8

96 well O' in 1 DNA Polymerase Premix

FYT201-96WL 96 Preps 23 µl x 96 Ask for price

Genorise® Plasma/Serum Viral DNA Extraction Kit 50

GR101036 50
EUR 87

DNA-BIND™ PLATE, 96 WELL, CLEAR, FLAT 1/10

2525 1/pk
EUR 164.4
Description: Genomics; Genomic Plates

Plasmid Extraction Maxi Plus Kit (10prep), Ion Exchange

FAPMX-010 10 preps
EUR 241.2

Plasmid Extraction Maxi Plus Kit (20prep), Ion Exchange

FAPMX-020 20 preps
EUR 337.2

ApexPrep DNA Plasmid Miniprep Kit

A5001-300 300 tests
EUR 338.4

ApexPrep DNA Plasmid Miniprep Kit

A5001-50 50 tests
EUR 115.2

Relaxed plasmid DNA - 0.050 mg

RDNA-050UG 0.050 mg
EUR 181.67
Description: This product includes 0.050 mg of relaxed plasmid DNA at 1 mg/ml in TE buffer

Deep Well Plate 96 Well 2.0 ML

AXYPDW20C PK50
EUR 196.8

96-well E. coli Topo IV DNA Cleavage Assay Kit Plus

T4C96KE 96 assays
EUR 597.7
Description: This product includes all the components in TDC96K plus 26 ul of 100 x E. coli Topo IV.

UNIFILTER PLATE 96 WELL 800 UL/WELL

WHA77002803 PK25
EUR 979.2

96 Deep Well Plate Square Well V

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EUR 322.8

96-well Topoisomerase DNA Cleavage Assay Kit (enzyme not included)

TDC96K 96 assays
EUR 510.52
Description: This product includes 300 ul of 10 x reaction buffer, 30 ul of 10 x DNA, 260 ul of SDS solution, 30 ul of 100 mM ATP, 260 ul of proteinase K solutions, 10 ml of TDC matrix, 6 ml of rinse buffer, 500 ul of 10 x dye, a black receiver plate, a V-bottom reaction plate and a TDC filter plate. Topoisomerase is not included in the kit. A plate filtration device (see Note below) and a vacuum line are needed for the plate filtration process.

Supercoiled plasmid DNA - 0.050 mg

SDNA-050UG 0.050 mg
EUR 160.91
Description: This product includes 0.050 mg of supercoiled plasmid DNA at 1 mg/ml in TE buffer

Solid 96 well plates

MC15F-BIO 10 plates(2X5 plates in a transparent bag)
EUR 215.17
Description: Solid 96 well plates BIOTIN COATED Color:Clear blocking:Standard

Solid 96 well plates

MC15F-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 283.21
Description: Solid 96 well plates BIOTIN COATED Color:Clear blocking:Non proteic

Solid 96 well plates

MCB15F-BIO 10 plates(2X5 plates in a transparent bag)
EUR 221.98
Description: Solid 96 well plates BIOTIN COATED Color:Black blocking:Standard

Solid 96 well plates

MCB15F-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 287.75
Description: Solid 96 well plates BIOTIN COATED Color:Black blocking:Non proteic

Solid 96 well plates

MCW15F-BIO 10 plates(2X5 plates in a transparent bag)
EUR 221.98
Description: Solid 96 well plates BIOTIN COATED Color:White blocking:Standard

Solid 96 well plates

MCW15F-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 287.75
Description: Solid 96 well plates BIOTIN COATED Color:White blocking:Non proteic

T4 DNA Ligase Plasmid

PVT7008 2 ug
EUR 614.4

ExoFectin Plasmid DNA-into-Exosome Kit (DNA transfection kit for exosome)

P402 - Ask for price

96-Well Topoisomerase DNA Decatenation Assay Kit (enzyme not included)

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EUR 526.61
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Plasmid ExtractionMaxi Plus Kit (10prep), EndoToxinFree, Ion Exchange

FAPMX-010-EF 10 preps
EUR 259.2

VAMNE Virus DNA/RNA Extraction Kit 3.0 (96 Prepackaged)

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EZ-10 Spin Column Plasmid DNA Miniprep Kit, Low Copy Plasmid

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EUR 105.67

EZ-10 Spin Column Plasmid DNA Miniprep Kit, Low Copy Plasmid

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Brand 96 Well Deep Well Plate-Stackable

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Genorise® Pure Plasmid DNA Mini Kit 100

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EUR 267

Genorise® Pure Plasmid DNA Mini Kit 200

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EUR 477

Genorise® Pure Plasmid DNA Mini Kit 500

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96 Well Deep Well Storage

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EUR 254.4

96 Well Deep Well Storage

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Relaxed plasmid DNA - 1 mg

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Description: This product includes 1 mg of relaxed plasmid DNA at 1 mg/ml in TE buffer

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EUR 115.85

Genorise® Pure Plasmid DNA Mini Kit 50

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EUR 149

96-well microplate sealer plastic

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EUR 94

Pure Plasmid 96 Miniprep Kit

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DEEP WELL PLATE 96 WELL 2.0 ML STERIL

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EUR 240

Plasmid DNA Maxiprep (10 preps)

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EUR 257.32

Plasmid DNA Maxiprep (30 preps)

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Supercoiled Plasmid DNA -1 mg

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EZ-10 Spin Column Plasmid DNA Min-preps Kit, Low Copy Plasmid

BS6149 250preps
EUR 251.05

EZ-10 Spin Column Plasmid DNA Miniprep Kit

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EUR 91.97

EZ-10 Spin Column Plasmid DNA Miniprep Kit

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EUR 114.82

1.2ML 96 WELL DEEP WELL PLATE HIGH CLARITY

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Description: Deep Well/Assay Plates - Axygen; Deep-well plates - Axygen

96-Well White Plates

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EUR 157.2

96-Well Black Plates

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Black 96 Well Plate, 1EA

X025-1EA 1EA
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96 Well Low DWP Round Well

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EUR 254.4

Adapter for 96 well plate

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EUR 6697.2

illustra GFx 96 Purification Kit 10 x 96 well plates

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EUR 1869.6

EZ-10 Spin Column Plasmid DNA Min-preps Kit

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96-well E. coli Gyrase DNA Cleavage Assay Kit Plus (enzyme included)

T2C96KE 96 assays
EUR 597.7
Description: This product includes 300 ul of 10 x reaction buffer, 30 ul of 10 x DNA, 260 ul of SDS solution, 30 ul of 100 mM ATP, 260 ul of proteinase K solutions, 10 ml of TDC matrix, 6 ml of rinse buffer, 500 ul of 10 x dye, a black receiver plate, a V-bottom reaction plate, 26 ul of 100 x E. coli Gyrase and a TDC filter plate. A plate filtration device and a vacuum line are needed for the plate filtration process.

96 Well Human Adult Normal Genomic DNA Plate - Peripheral Blood Leukocyte

D8234148-1 1 plate
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Benchmark Beadblaster 96 Eva Cap Mat for 96 Well Deep Well Plate

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96-Well Plate PCR Products Purification Kit

BS365 5XPlates, 480prep
EUR 300.37

96-Well Plate PCR Products Purification Kit

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EUR 186.19

EZ-500 Spin Column Plasmid DNA Maxi-preps Kit

BS4654 4preps
EUR 150.92

EZ-500 Spin Column Plasmid DNA Maxi-preps Kit

BS466 20Preps
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96-Well Human Topo II DNA Decatenation Assay Kit Plus (enzyme included)

HDD96KE 96 assays
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Description: This product includes the assay buffer, concatenated DNA, human topo II alpha, ATP, fluorescence dye, rinse buffer and a TDD filter plate for 96 assays of human topo II DNA decatenation reactions.

EZ-10 Spin Column Yeast Plasmid DNA Miniprep Kit

BS467 10Preps
EUR 78.28

EZ-10 Spin Column Yeast Plasmid DNA Miniprep Kit

BS468 50Preps
EUR 133.08

EZ-10 Spin Column Yeast Plasmid DNA Miniprep Kit

BS469 250preps
EUR 364.32

96-Well E. coli gyrase DNA Decatenation Assay Kit Plus (enzyme included)

T2DD-96KE 96 assays
EUR 591.41
Description: This product includes the assay buffer, concatenated DNA, E. coli gyrase, ATP, fluorescence dye, rinse buffer and a TDD filter plate for 96 assays of E. coli gyrase DNA decatenation reactions.

96 well plates - 12x8 Well Strips on 12x8 frame

MT0STF2-SA5-200 10 plates(2X5 plates in a transparent bag)
EUR 262.8
Description: 96 well plates - 12x8 Well Strips on 12x8 frame STREPTAVIDIN COATED Color:Clear blocking:Standard

96 well plates - 12x8 Well Strips on 12x8 frame

MT15F2-BIO 10 plates(2X5 plates in a transparent bag)
EUR 217.44
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:Clear blocking:Standard

96 well plates - 12x8 Well Strips on 12x8 frame

MT15F2-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 285.48
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:Clear blocking:Non proteic

96 well plates - 12x8 Well Strips on 12x8 frame

MTB15F2-BIO 10 plates(2X5 plates in a transparent bag)
EUR 219.71
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:Black blocking:Standard

96 well plates - 12x8 Well Strips on 12x8 frame

MTB15F2-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 287.75
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:Black blocking:Non proteic

96 well plates - 12x8 Well Strips on 12x8 frame

MTW0STF2-SA5-200 10 plates(2X5 plates in a transparent bag)
EUR 265.07
Description: 96 well plates - 12x8 Well Strips on 12x8 frame STREPTAVIDIN COATED Color:White blocking:Standard

96 well plates - 12x8 Well Strips on 12x8 frame

MTW15F2-BIO 10 plates(2X5 plates in a transparent bag)
EUR 219.71
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:White blocking:Standard

96 well plates - 12x8 Well Strips on 12x8 frame

MTW15F2-BIO-W 10 plates(2X5 plates in a transparent bag)
EUR 287.75
Description: 96 well plates - 12x8 Well Strips on 12x8 frame BIOTIN COATED Color:White blocking:Non proteic

Aligned Nanofibers 96 Well Plate

3D00012-96 700 nm-PCLs
EUR 132

96-well Total RNA Kit (1 plates)

FATRE-96001 1 prep
EUR 232.8

96-well Total RNA Kit (2 plates)

FATRE-96002 2 preps
EUR 337.2

96-well Total RNA Kit (4 plates)

FATRE-96004 4 preps
EUR 537.6

Exosomal DNA Extraction Kit

P230-25 - Ask for price

Exosomal DNA Extraction Kit

P230-50 - Ask for price

96-Well CometSlides

4253-096-03 1 Tests
EUR 170.88

96-Well S. aureus gyrase DNA Decatenation Assay Kit Plus (enzyme included)

T2DD-96KS 96 assays
EUR 681.29
Description: This product includes 600 ul of 10 x assay buffer, 500 ul of 10 x concatenated DNA, 120 ul of 10 mM ATP, 100 ul of 50 x S. aureus gyrase, 600 ul of Stop solution (0.4 M EDTA), 500 ul of 10 x fluorescence dye, 2 ml of 10 x rinse buffer, one V-bottom plate, a TDD filter plate and one black 96-well plates for 96 assays of DNA decatenation reactions.

Avidin CovaLinked 96-well Plates

6521-5 each
EUR 306

Greiner polystyrene 96 well plates

M2311-100EA PK100
EUR 192
The predictions recommend that these therapies for lung supply ought to ideally be delivered in a sustained launch formulation with excessive solubility for optimum native publicity in lungs for efficacy, with fast systemic clearance in plasma for diminished danger of undesirable systemic antagonistic results. This work exhibits the potential advantages of BPMX and the position it may play to help drug discovery and growth in pulmonary supply.

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