Solution calorimetry as an alternative approach for dissolution testing of nanosuspensions

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Nanocrystal/nanosuspension formulations are advanced drug delivery systems enhancing oral bioavailability.
• Rapid dissolution rates of these formulations necessitate precise analytical methods for monitoring.
• Current analytical techniques may struggle to capture the extremely fast dissolution kinetics of nanosuspensions.

Purpose of the Study:

• To evaluate solution calorimetry as a novel analytical technique for measuring the dissolution rate of drug nanosuspensions.
• To assess the feasibility of monitoring the rapid dissolution process of nanocrystals using temperature changes.
• To investigate the applicability of solution calorimetry across different model drugs and an investigational API.

Main Methods:

• Utilized solution calorimetry to record temperature changes during the dissolution of nanosuspensions in a dissolution vessel.
• Tested the method on nanosuspensions of three model drugs: naproxen, cinnarizine, and an investigational API (compound A).
• Collected sufficient data points during the rapid dissolution process (completed within 1 minute) for analysis.

Main Results:

• The dissolution of all tested nanosuspensions was completed in under 1 minute.
• Temperature offset data was successfully converted to cumulative heat of solution, indicating the technique's potential.
• Solution calorimetry captured the rapid dissolution kinetics of the drug nanocrystals.

Conclusions:

• Solution calorimetry shows potential for measuring the dissolution rates of rapidly dissolving nanosuspensions.
• Accurate interpretation requires accounting for all thermal events, including the heat of mixing, to avoid erroneous conclusions.
• Further refinement is needed to isolate dissolution heat from other process-related thermal changes.