IDR Imaging

The Intrinsic Dissolution Rate (IDR) is a measure of the rate of dissolution of a pure active pharmaceutical ingredient (API) where the conditions of surface area, temperature, agitation/stirring speed, medium pH and ionic strength are all kept constant. A well-defined surface area is presented to the dissolution medium by preparing a flat tablet disc of specific size. IDR is important during the development of new drug molecules as it is possible to predict potential problems using small quantities of material.

It has applications in evaluating drug solubility in accordance with the biopharmaceutics classification system (BCS), comparison of the dissolution rate during salt selection or polymorph screening to choose the best candidate, and setting specifications for particle size in order to achieve complete dissolution of the required dose within the typical gastrointestinal transfer time. Disc IDR imaging can be applied to promising drug candidates to guide early development efforts to improve a drug’s in vivo characteristics.

20 – 50 mg of dry compound is required for this assay.

The IDR (mass/time/area) for each sample is determined for the chosen buffer system. Images of the dissolution process are recorded. A full study report is provided.

In the disc method, the drug powder is compressed into discs of fixed diameter. Theoretically, this results in an exact and constant surface area that is in contact with the dissolution medium during the full time of the experiment, and this is the major advantage of this method. The miniaturized commercially available device, the SDi2 (Surface Dissolution Imaging) platform, is used to record images of the dissolution process at the surface of the compact and is able to rank-order DIDR (µg/min/cm2) and visualise the dissolution of APIs and salts during early development.

The Surface Dissolution Imaging IDR measurement is based on flow-through dissolution and direct UV imaging of the flow-cell. The technique records the release of material directly from the surface of a 3mm compacted disc of API and from near downstream to calculate IDRs. The instrument comprises a sample flow cell, pump system, light source and ActiPix detector, and control and data analysis software. The ActiPix detector uses a complementary metal oxide semiconductor (CMOS) image sensor containing over 4 million pixels for recording light transmission through the flow cell. Light at pre-selected single wavelengths (selected between 255 – 520 nm) is flashed at pre-set time intervals and is used to illuminate the flow cell.

A pump is used to flow buffer at a pre-set controlled temperature through the flow cell. The transmitted light in the presence of flowing medium is captured by the detector during the sample run and the light intensity at each pixel is converted into an absolute absorbance. The images collected for the duration of the experiment are used to create a movie that provides a detailed view of the dissolution process at the solid–liquid interface and downstream of the compact.  Applying proprietary software tools then allows extraction of standard disc intrinsic dissolution rate values of (mass/time/area) which are easily calculated from the volumetric flow rate and the absorbance values downstream of the compact.