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SiriusT3

Pion’s SiriusT3 is a fully automated instrument designed for compound screening and preparing detailed PhysChem profiles. The Sirius lets you use Pion’s proprietary CheqSol method to accurately determine the kinetic and intrinsic solubilities of ionizable compounds. It generates detailed information about the extent and duration of supersaturation and a pH-solubility profile from a single, highly automated assay which takes less than 2 hours.

‘SiriusT3 is the Gold Standard.’

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Overview

The SiriusT3 is an essential tool for analyzing pure single-component organic chemicals and their salts. It measures pKa, logP, logD and solubility of ionizable drugs and small molecules, needing only very small amounts of sample. It is widely used in industrial and university labs, CROs and Pharma to support drug discovery research.

Customers describe the SiriusT3 as ‘integral’ for the physicochemical characterization of compounds and ‘a pre-requisite for DMPK studies’. Others praise how it ‘integrates perfectly’ into analytical workflow and how it can ‘aid in the selection of compounds to move forward into further PK testing’.

Applications

The SiriusT3 supports a range of tasks across early stage compound screening, physchem characteriza-tion and pre-formulation. These include:

  • Determining intrinsic solubility
  • Measuring pKa in synthetic chemistry to help select the best structures for development
  • Ensuring good compound selection to reduce the risk of late stage failures
  • Understanding the ionization state of a drug, how it varies with pH and its effect on absorption
  • Learning how the pKa changes due to solvent interactions, partitioning, precipitation or binding
  • Improving ADME predictions and evaluating how changes to the molecule can affect the logP for a desired application
  • Learning about a molecule’s capacity for supersaturation

Features

Accuracy

The Pion pH-metric method provides independent confirmation that ionization has occurred and also helps characterize acidic and basic groups, in addition to logP and solubility. This eliminates the need for time-consuming shake-flask style experiments in multiple pH buffers.

LogP can be potentiometrically determined and logD vs. pH can be accurately derived from measured logP and pKa data. Likewise, equilibrium solubility vs pH can be derived from potentiometrically de-termined intrinsic solubility and pKa data. Partitioning behavior between water and octanol, toluene, dodecane and with other solvents can also be studied, along with the effects of excipients and co-solvents on solubility. The instrument comes with built-in methods for measuring compounds of high, medium and low logP, and for determining solubility of samples with differing precipitation behavior

Speed

With the SiriusT3, you can determine pKa values to the highest accuracy available commercially, with results in 15 minutes by Fast UV for most samples. It uses the UV-metric method for pKas below 2 and above 12; cosolvent methods for poorly soluble samples; pH-metric assays for samples without UV activity. Sample requirement:  UV, 10 μg; pH-metric, 1 mg.

Simplicity

Many assays work with standard templates. Templates are supplied for all supported assays, including a 1-2-3 template for setting up co-solvent pKa assays. You can also save customized templates if re-quired.

Efficiency

The SiriusT3 makes measurements using small amounts of sample. Assays are performed in solution, 1 - 3 mL. Solutions are prepared in vials via automated dispensers and temperature-controlled be-tween 12 - 70°C..A built-in ultra-sonic bath helps to dissolve poorly soluble compounds. In addition, by running clean-up assays, you can ensure that the SiriusT3 is always ‘ready to go’.

Robotics

SiriusT3 has a fully automated X and Y axis on a titrator module probe arm, which is fully equipped for automatic reagent delivery, stirring, spectra collection, pH measurement and temperature control. This allows you to run complicated assays that could be challenging to set up manually.

Automation

The optional autoloader improves convenience and high throughput capabilities as experiments can be run unattended.

Resources

Acidity constants of hydroxyl groups placed in several flavonoids: Two flavanones, two flavones and five flavonols

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Trends in oral small-molecule drug discovery and product development based on product launches before and after the Rule of Five”

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Advanced in vitro methods in generic drug product development

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"Utilizing Pion's SiriusT3 Platform" Webinar

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Applying Computational Predictions of Biorelevant Solubility Ratio Upon Self-Emulsifying Lipid-Based Formulations Dispersion to Predict Dose Number

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SiriusT3 Product Brochure

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Extended Instrument Shut Down for Sirius T3 Storage Guidelines

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Diclofenac Prodrugs for Intra-articular Depot Injectables: In Vitro Hydrolysis and Species Variation

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Comparison of Cinchona Catalysts Containing Ethyl or Vinyl or Ethynyl Group at Their Quinuclidine Ring

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pKa and physchem property measurements for the pharmaceutical industry

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WEBINAR: How pKa Values are used in the Pharmaceutical Industry

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WEBINAR: Understanding and Measuring pKa

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LogP as a tool in intramolecular hydrogen bond considerations

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Effect of vinylpyrrolidone polymers on the solubility and supersaturation of drugs; a study using the Cheqsol method

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Acid‐base titrations of proteins in small volumes

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The impact of cosolvent on measured log P values

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Determination of hydrogen bonding properties using logP

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Surface tension and supersaturation

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Measuring the isoelectric point of peptides by potentiometric titration

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Solubility Measurement

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Measuring Physiochemical Properties

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WEBINAR: Measuring solubility - what’s best for you?

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WEBINAR: Physicochemical Properties and their relation to ADMET

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WEBINAR: How Cheqsol Works

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WEBINAR: Investigating Supersaturation and Solubility Enhancement

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WEBINAR: State of the art UV methods for measuring pKa

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WEBINAR: Accessing hydrogen bond parameters and their application in drug discovery

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WEBINAR: Log P- History, Measurement and Applications in Drug Development

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Early pharmaceutical profiling to predict oral drug absorption: Current status and unmet needs

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Novel N-methylsulfonamide and Retro-N-methylsulfonamide Derivatives as 17b-Hydroxysteroid Dehydrogenase Type 2 (17b-HSD2) Inhibitors with Good ADME-Related Physicochemical Parameters

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Partial Protection Against Multiple RT-SHIV162P3 Vaginal Challenge of Rhesus Macaques by a Silicone Elastomer Vaginal Ring Releasing the NNRTI MC1220

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Physicochemical investigation of the influence of saccharide-based parenteral formulation excipients on l-p-boronphenylalanine solubilisation for boron neutron capture therapy

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Cyclopentane-1,3-dione: A Novel Isostere for the Carboxylic Acid Functional Group. Application to the Design of Potent Thromboxane (A2) Receptor Antagonists

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The ‘‘GI dissolution’’ method: a low volume, in vitro apparatus for assessing the dissolution/precipitation behaviour of an active pharmaceutical ingredient under biorelevant conditions

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Structural and thermodynamic analyses of alpha-L-fucosidase inhibitors

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New ideas about the solubility of drugs

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Assessment of distribution- pH profiles

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Multiwavelength spectrophotometric determination of acid dissociation constants Part VI. Deconvolution of binary mixtures of ionizable compounds

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Physicochemical characterization of sildenafil: Ionization, lipophilicity behaviour, and ionic-partition diagram studied by two-phase titration and electrochemistry

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Ionization Constants and Ionization profiles

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Measuring Physiochemical Properties 2

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4‐case chart to classify supersaturation and precipitation behavior

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Measuring pKa values in 2-propanol to gain process understanding

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Ionization Constants of Isoniazid and Benzimidazole

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pH-metric titration to characterize aci-nitro tautomerism

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Effects of solubility enhancing excipients

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Faster Dissolution Methods

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Low Volume Dissolution Assays

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The effect of dissolution media, torque and flow speed

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Biphasic dissolution studies of Felodipine

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Dissolution & precipitation studies of carbamazepine cocrystals with small scale assays

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Dissolution in presence of lipid to mimic absorption

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Dissolution Experiments in Lipid Layers

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Small scale assays for studying dissolution of cocrystals

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Small volume dissolution of a poorly soluble drug as solid dispersions

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Solubility of drugs in the presence of excipients in lipid based formulations

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Supersaturation & precipitation of ionizable drugs with cellulose polymers

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Physicochemical Studies of Triclosan

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Simulated Lung Fluid media

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Solubility measurement by extrapolation

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Solubilities of morphine analogs

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Characteristics of Felodipine ‐ HPMCAS Solid Dispersions

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Dissolution Performance of Inhaled Products in Simulated Lung Fluid

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In-situ Solubility Measurements of Ionizable Drugs

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Determination of Aqueous Solubility by Extrapolation

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A low volume method for screening Plasdone® polymers

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Assay Expert Flyer

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AN410 Measuring the isoelectric point pf peptides by potentiometric titration

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AN15 Determination of pKa Measurement or Prediction?

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AN14 Using NaOH and NaCL instead of KOM and KCI

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AN13 Measuring Solubility What’s Best for You?

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AN12 Introduction to logP and logD Measurement Using SiriusT3

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AN10 Measuring LogP of Samples that are Hard to Dissolve in Water and Octanol

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AN09 The Determination of Solubility - Pion CheqSol Explained

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AN08 Solubility and Supersaturation - A Brief Introduction

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AN07 the Pion GI Dissolution Assay

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AN06 The use of cosolvent pKa assays for poorly soluble compounds

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AN05 Measurement of extreme pKas

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AN04 Insights into BCS classification using Pion assays

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AN03 Blank Titrations Using the SiriusT3

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AN02 PKa measurements in 15 minutes - the SiriusT3 Fast UV pKa method

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AN01 High quality measurements for small sample amounts

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Pion SDi2 and Raman spectroscopy - study of diclofenac sodium salt

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Behavior of Basic Compounds in the Presence of Plasdone Polymers

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Determination of pKa values and Solubility pH Profiles of Selected ß blockers

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Supersaturation in additives and GI fluids

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Validation of titrimetric measurement of pKa, logP and solubility

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The intrinsic solubility of indomethacin

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Measuring the solubility of salts of basic drugs

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Potentiometric techniques for measuring solubility at 37°C

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Karl Box Sunrise Presentation

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Determination of Polymer Effectiveness

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Utilization of pH-Metric Titration

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Consumables

2.5mL Plunger

T306034

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0.5mL Plunger

T306033

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T3 - Three Capillary Assembly

T306036(3)

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T3 - Five Capillary Assembly

T306036(5)

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T3 - Six Capillary Assembly

T306036(6)

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SiriusT3 - Mini-electrode

T485024

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T3 - Sample Vials - Pack of 1000

T304036

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T3 - Sample Vials - Pack of 100

T304037

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T3 - Sample Vial Caps - Pack of 100

T304038

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Wash Vial - Pack of 2

T304041

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Buffer Vial - Pack of 5

T304042

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T3 - Extended Life Deuterium Lamp

T409004

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48 well vial rack

T210046

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Stainless Steel Vial Rack

T210049

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Ultrasonic Bath Cover

T210050

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PEEK Electrode Block Rev G

T210045

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Electrode Block Skirt

T210051

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Waste Bottle

T305119

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Wash Water Bottle

T305120

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250mL Bottle

T305083

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500mL Bottle

T305084

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250mL Machined Bottle Top

T305086

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250mL Bottle Top Plate (1 hole)

T305089

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T3 - pH7 Buffer

1402002

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T3 - Neutral Linear Buffer

T1404007

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T3 - Electrode Filling Solution - Pack of 2

1402012

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Mini Stirrer Assembly MKII

T1015066

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Mini Bubbler

T210047

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