Research Capabilities

Chemistry

• Prodrug design and synthesis
• Peptide and small molecule synthesis (mg to multigram scale)
• Reference standard preparation
• Separation and purification with the Companion automated flash chromatography system
• Microwave synthesis technology for improved yield and efficiency

Physicochemical Profiling


• Log P/Log D determinations using traditional ‘shake-flask’ methods
• Measurements of aqueous solubility under physiologically relevant conditions
• Assessment of impurity profiles
• Short and long term stability studies, accelerated stability testing, and pH degradation rate profiling, using rugged stability indicating assays
• Melting point determinations using Differential Scanning Calorimetry
• Plasma protein binding determined using equilibrium dialysis

Dosage Form Development


• Solid, liquid, and multiparticulate dosage form development capabilities
• Direct blend, low shear, high shear, and fluid bed granulation processing
• Single punch tablet press
• Extrusion/spheronization
• Fluid bed coating (ascetic and functional)
• USP 2 dissolution apparatus (flow through set-up)
• Controlled and sustained drug delivery systems
• Unique solutions for water insoluble drugs

Bioavailability and Pharmacokinetics
 
The ADME properties of a selected compound are examined after intravenous, oral or intra-peritoneal (IP) administration to small laboratory animals such as mice, rats or rabbits. Several different vehicle formulations may be used to solubilize compounds depending on the route of administration. LC/MS/MS is used for the quantification of compounds in typically plasma, urine or feces.  Other biological matrices that may be analyzed include red blood cells, brains, liver, lung, kidney or muscle. Drug extraction procedures are developed using liquid phase or solid phase extraction methods. The quantification by LC/MS/MS provides rapid method development and high specificity and sensitivity to the nanogram or even picogram levels.

Metabolite identification can be assessed in parallel with quantitation analysis using the Applied Biosystems 3200 QTRAP triple quadrupole, linear ion trap mass spectrometer.

In Vivo Screening

• Culex automated in vivo sampling system for collecting blood, urine and feces from awake and freely moving animals
• Small animal pharmacokinetics and pharmacodynamics
• Bioavailability studies
• Prodrug conversion studies
• Toxicity studies
• Efficacy evaluations in animal models
• Small animal behavioral evaluations (Forced Plate Actimeter)
• Small animal imaging studies

Other Analytical Tools


• Chromatography (reversed phase, ion exchange, size exclusion) method development using UV, fluorescence, evaporative light scattering or mass detection for the separation and analysis of drug candidates
• UV-Vis spectroscopy
• Separation of ionic species on the basis of charge differences by capillary electrophoresis for compounds with little physical difference
• Enzyme-linked ImmunoSorbent Assay (ELISA) for the determination of serum antibody concentrations.

Bio-Molecule Assays


• SDS-PAGE or Native-PAGE to identify and semi-quantitatively evaluate specific protein levels.
• Gel electrophoresis followed by Western blotting with antibodies targeting specific proteins is used to evaluate the effect of therapeutic compounds on the level of proteins or protein complexes and can be a valuable tool to screen new compounds both in animal models and cell lines.
• Enzyme-linked ImmunoSorbent Assay (ELISA) for the quantitative determination of specific proteins.

Cell Based Assays


• Dedicated lab for tissue culture, cell culture and cell based screening assays.
• The Countess automated cell counter is used for automatic calculation of the number of viable cells available and determining the amount of suspension required for the assay plate.
• IC-50 cytotoxicity determinations using a variety of cell lines can be performed in a high throughput manner in 96 well and 384 well plates with automated compound dilution and delivery using the Tecan®Evo 75 robot.
• The Caco-2 cell monolayer in vitro model is used to assess the permeability of new drug candidates. An apparent permeability coefficient (Papp) is determined by measuring the permeability of compounds across the cell monolayer. The permeability coefficient is used to rank compounds as poorly permeable, moderately permeable or highly permeable relative to drug standards which have been well characterized. This model is also used to indicate whether a compound is potentially a substrate for p-glycoprotein transportation, by determining the apparent permeability with and without the presence of a potent P-gp inhibitor.