An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution.

Area of Science:

• Pharmaceutical Science
• Drug Development
• Analytical Chemistry

Background:

• Intrinsic dissolution rate (IDR) is crucial for characterizing drug substances and formulations.
• Accurate IDR measurement aids in predicting drug behavior in vivo.
• Standardized methods are needed to ensure reliable IDR data across different laboratories.

Purpose of the Study:

• To evaluate the interlaboratory performance of surface dissolution imaging (SDI) equipment for IDR measurement.
• To assess the robustness of a standardized protocol for IDR determination using SDI.
• To compare SDI performance with existing IDR measurement techniques.

Main Methods:

• An interlaboratory ring study involving six academic and industrial partners was conducted.
• Six drugs with varying solubilities (low, medium, high) were tested using a standardized operating procedure.
• Fasted State Simulated Intestinal Fluid (FaSSIF) at pH 6.5 was used as the dissolution medium.

Main Results:

• The study successfully obtained IDR values for all tested compounds using the standardized SDI protocol.
• The overall rank order of measured IDR values corresponded to the known solubility rank order of the drugs.
• Higher interlaboratory variability was observed for low-solubility compounds (CV >50%), indicating potential challenges in reproducibility.

Conclusions:

• Surface dissolution imaging (SDI) demonstrates robust performance in measuring intrinsic dissolution rate (IDR).
• The standardized protocol provides reliable IDR data, aligning with drug solubility profiles.
• While SDI shows promise, further investigation into variability for low-solubility compounds is warranted.