Gold Standard Assays
Sirius Analytical Gold Standard assays are definitive physchem analyses in which the analysis conditions are optimised to give the best data quality. We perform repeat analyses until the best result is achieved. The assays are typically designed for solids, although solutions can also be accommodated.
Extended investigations are available to study additional sample attributes such as changes in polymorph/crystal form for example.
The Sirius Gold Standard pKa assay is a definitive PhysChem assay that is customised for each compound using either a pH-metric or UV-metric approach. It may therefore be used for compounds which are non UV active. The pH-metric pKa range is 2-12 and the dual vial UV method measures pKas in the range 1.5 to 13.5. Either aqueous or cosolvent approaches are adopted depending upon the compound solubility. A detailed report is provided including:
- pKa results (triplicate determination as standard for aqueous assays)
- Method overview
- Titration or difference curves
- Distribution of species plot
- Ionic strength profile
- Molar absorption profiles (in cases where the pH-UV method is applied)
Samples are typically provided as solids for Gold Standard pKa assays. We normally request 5mg for this assay, but smaller amounts can be accommodated, so please talk to Sirius if you intend to submit less.
Our pH-metric LogP assay is a definitive Physchem assay for compounds which are ionisable. The assay yields the LogP of neutral and ionic forms of an ionisable compound. This assay also delivers an extrapolated pH vs. LogD profile. Ocan-1-ol is used as our standard partition solvent but alternative partition solvents can be accommodated at additional cost. The method will accommodate compounds having a LogP value between -1 and 6.
Samples are typically provided as solids for Gold Standard LogP assays. We normally request 5mg for this assay, but smaller amounts can be accommodated, so please talk to Sirius if you intend to submit less.
Sirius offers several methods for measuring solubility to accommodate a range of customer requirements:
Shake flask Equilibrium Solubility
Classic, customisable solubility investigations at fixed pH values using low volume apparatus with UV or HPLC detection. Standard assays use UV quantitation. HPLC based assays are available for samples which have very low solubility, may decompose or are relatively impure. These assays can be conducted in the presence of biorelevant buffers such as FaSSIF and FeSSIF.
Solubility, supersaturation and precipitation studies
The pH-metric solubility assay is a powerful analytical tool which will yield the kinetic and intrinsic solubility of the neutral species and a calculated pH-solubility profile, together with information on the extent and duration of supersaturation. The assay can be conducted in the presence of biorelevant buffers such as FaSSIF and FeSSIF.
Our dissolution assay is a small volume assay which uses in-situ tools to monitor the release of drug into solution over time. Our capabilities include real-time pH control in the vessel and measurement in the presence of excipients and bio-relevant buffer media including FaSSIF and FeSSIF simulated intestinal fluids. This assay is ideal for formulation development work and gives valuable insight into the impact of pH and the presence of additives on drug dissolution.
Relevant Application Note:
AN07 The Sirius GI Dissolution Assay
Sirius undertakes studies in particle size and shape analysis using laser obscuration time and image analysis techniques. These analyses are ideally suited to studying particles in liquid suspension and offer a way of characterising size without assuming particle shape or the need to know optical properties of the sample. Particle shape is described by a number of different shape parameters which describe your particles in greater detail than particle size alone. Powders can be readily dispersed in a non-dissolving liquid and viscous liquids such as creams and ointments can be characterised using a measurement cell which accommodates a microscope slide. The liquid dispersion technologies are particularly suitable for studying dynamic processes such as dissolution, crystallisation and disintegration.
Relevant Application Note:
AN201Particle size analysis related to dissolution and crystallisation studies
AN202 Number and volume distributions in particle size analysis
AN203 Particle size analysis of non-spherical particles
AN204 Studying dynamic processes using particle size analysis
We partner with a leading UK university who employs cutting edge solid state techniques including X-ray powder diffraction (XRPD), microscopy, Differential Scanning calorimetry (DSC) and thermogravimetric (TGA) analyses directly to samples provided by customers, or to precipitates generated during solubility or dissolution experiments.
FaSSIF and FeSSIF measurements are made using simulated intestinal fluids (SIF) provided by Biorelevant.