Mechanism of drug release from temperature-sensitive formulations composed of low-melting-point microcrystalline wax.

It was reported that wax matrix (WM) particles composed of low-melting-point microcrystalline wax showed unique release behaviors; the particles released only a small amount of the entrapped drug (non–diffusion-controlled release) at 37°C, whereas it showed comparatively fast drug release in a diffusion-controlled manner at 25°C. However, the mechanism of the drug release is still unclear. The objective of this study was to determine the mechanism of drug release from the WM particles using X-ray computed tomography. In the WM particles collected during dissolution tests at 25°C, the void space derived from drug release increased with increasing time, and there was no change in the structure, indicating that the WM particles released drug while maintaining the particle shape at 25°C. In the WM particles collected during dissolution tests at 37°C, the void space was confirmed at initial time point; however, at subsequent time points, the void space was disappeared, and the roughness of the surface was evident. This structural change may have blocked the conveyance pathway of the outer medium, which would inhibit the drug release. The difference between the drug-release mechanisms of the WM particles at the 2 temperatures will be valuable for developing cooling-triggered, temperature-sensitive formulations.