Formulation and Development

Gold Standard pK_a

pK_a measured either potentiometrically, or spectroscopically, using our industry standard pH-metric and pH-UV methods. Assays can be run under aqueous or cosolvent conditions. Our standard practice is to attempt an aqueous determination first, and only if the compound fails under aqueous conditions do we proceed to a cosolvent determination. In such cases, only the cosolvent price is charged. Real-time turbidity detection is used to detect whether the compound is dissolved or not. If the compound does precipitate, the exact pH of precipitation is reported.

Requires:

-          5 to 10mg of solid (contact us if you have smaller quanities)

-          Structural information (Full structure, partial structure, or list of ionizable groups)

Delivers:

-          pK_a results (triplicate determination as standard)

-          Method overview

-          Titration curves

-          Distribution of species plot

-          Ionic strength profile

-          Buffer capacity profile

-          Molar absorption profiles (in cases where the pH-UV method is applied).

Gold Standard LogP/D

Measures the logP of the compound, by titrating it in water/octanol mixtures.  Measures neutral logP and ion‐pair logP. LogD vs. pH profile generated for pH 2 to 12. Determination is performed in triplicate.

Requires:

-          5 to 10mg of solid (contact us if you have smaller quanities)

-          Structural information (Full structure, partial structure, or list of ionizable groups)

-          Measured pK_a(s)

Delivers:

-          logP results (triplicate determination as standard)

-          logD results extrapolated at specified pH values

-          Method overview

-          Titration curves

-          Distribution of species plot

-          Lipophilicity (pH vs. logD) plot

-          Ionic strength profile

Gold Standard Solubility

Intrinsic & Kinetic Solubility measurement using pH-metric methods. Degree of supersaturation also determined. Real-time monitoring of pH change can sometimes reveal polymorph formation during precipitation and dissolution cycles.

Requires:

-          5 to 20mg of solid (contact us if you have smaller quanities)

-          Structural information (Full structure, partial structure, or list of ionizable groups)

-          Measured pKa(s)

Delivers:

-          Intrinsic Solubility result

-          pH dependent solubility results extrapolated from pH 2 to pH 12

-          Method overview

-          Titration curves

-          Distribution of species plot

-          Solubility (pH vs. logS) plot

-          Ionic strength profile

Gold Standard GI Dissolution

Dissolution measured by UV absorbance in our unique GI simulator cell, where the pH of the bulk solution can be varied to simulate passage of a drug through the GI tract.

Requires:

-          5 to 20mg of solid (contact us if you have smaller quanities)

-          Structural information (Full structure, partial structure, or list of ionizable groups)

Delivers:

-          Dissolution rates in each pH zone

-          Time vs. Concentration profile

-          Method overview

Gold Standard PhysChem Bundle

pK_a, logP, and solubility measurement by our pH-metric and UV-hybrid methods

Requires:

-          20 to 50mg of solid (contact us if you have smaller quanities)

-          Structural information (Full structure, partial structure, or list of ionizable groups)

Delivers:

-          pK_a, logP & solubility information detailed above.

XRPD (X-Ray Powder Diffraction)

XRPD is used to characterize and identify phases. The advantages of the technique are simplicity of sample preparation, speed of measurement and the ability to analyze mixed phases. Since all possible crystal orientations are measured simultaneously, collection times are short even for small and weakly scattering samples. This is essential for samples which are unstable either inherently or under x-ray bombardment, or for time-resolved studies. Relative to other methods of analysis, powder diffraction allows for rapid, non destructive analysis of multi-component mixtures without the need for extensive sample preparation.

Requires:

-          At least 200mg of solid in dry, crystalline powder form

Delivers:

-          Diffraction pattern, plot of Counts vs. 2Ø/º.

XRPD Structure Comparison

Spectrum collected from XRPD will be compared with spectra from PDF or CSD. The result will comprise a short report. Identification is performed by comparison of the diffraction pattern to a known standard or to a database such as the international Centre for Diffraction Data's Powder Diffraction File (PDF) or the Cambridge Structural Database (CSD). The most widespread use of powder diffraction is in the identification and characterization of crystalline solids, each of which produces a distinctive diffraction pattern. Both the positions (corresponding to lattice spacing's) and the relative intensity of the lines are indicative of a particular phase and material.

Requires:

-          XRPD data

Delivers:

-          Report of findings

DSC (Differential Scanning Calorimetry)

The result will comprise a plot of Heat Flow vs. Temperature. The result of a DSC experiment is a curve of heat flux versus temperature or versus time. Differential scanning calorimetry can be used to measure a number of characteristic properties of a sample. Using this technique it is possible to observe fusion and crystallization events as well as glass transition temperatures. In the pharmaceutical industry it is necessary to have well-characterized drug compounds in order to define processing parameters. For instance, if it is necessary to deliver a drug in the amorphous form, it is desirable to process the drug at temperatures below those at which crystallization can occur. DSC curves may also be used to evaluate drug and polymer purities. This is possible because the temperature range over which a mixture of compounds melts is dependent on their relative amounts. Consequently, less pure compounds will exhibit a broadened melting peak that begins at lower temperature than a pure compound. Samples can be run open to the purge gas or hermetically sealed; for hydrates and solvates the conditions can make a significant difference to the results expected and obtained.

Requires:

-          At least 10mg of solid of sample in dry, crystalline powder form

Delivers:

-          Heat Flux vs. Temperature or Heat Flux vs. Time plot.

TGA (Thermogravimetric Analysis)

TGA is performed on samples to determine changes in weight in relation to change in temperature. These changes can indicate degradation temperatures, adsorbed moisture content and, for hydrates and solvents, some estimate of composition.

Requires:

-          At least 50mg of solid of sample in dry, crystalline powder form

Delivers:

-          Change in mass (mg) vs. Time plot

-          Derivative change in mass plot

Solid State Bundle (XRPD + DSC + TGA)

Discounted bundle of all three solid state measurements

Requires:

-          At least 250mg of dry,crystalline solid

Delivers:

-          All solid state information detailed above.

Polymorph Creation by Potentiometric Cycling (PC)2 Study

Compound run through an extended CheqSol assay with multiple potentiometric cycles, to study for the evidence of polymorph formation during the cycling process. If polymorphism is observed, further work is performed to isolate the individual species precipitating, and have them analysed by the XRPD + DSC + TGA bundle to identify the solid state forms of the precipitates.

Requires:

-          At least 400mg of solid

-          Structural information (Full structure, partial structure, or list of ionizable groups)

Delivers:

-          Gold-Standard solubility data.

-          Discussion of behaviour - i.e. if any polymorphs are observed

-          Solid state bundle information if polymorphism discovered