Nanocrystal Formation of Hydrochlorothiazide: Effect of a Surfactant on the Solid-State Properties

Background: Modification of solid-state properties is associated with nanocrystallization of drug substances, and crucial to processability of materials during formulation. This work was aimed at assessing the effect of a surfactant on the solid-state properties in nanocrystal formation of hydrochlorothiazide.

Methods: The drug powder was subjected to two forms of nanocrystallization: with and without the inclusion of Tween 80, a surfactant. The two generated nanocrystal forms, in comparison with the unprocessed drug, were subjected to Fourier transform infrared spectroscopy, differential scanning calorimetry and particle size analysis.

Results: All the major peaks in the FTIR spectrum of hydrochlorothiazide powder (HCTZ1) were retained in the spectrum of crystals generated without the addition of Tween 80 (HCTZ2) and in that of the crystals generated with the addition of Tween 80 (HCTZ3). The thermogram of HCTZ1 showed a sharp endothermic transition with a peak at 77 0C followed by a diffuse endotherm with a peak at 235 0C; that of HCTZ2 was characterized by a diffuse endotherm with a peak at 110 0C and a diffuse exotherm with a peak at 250 0C while that of HCTZ3 was characterized by a single endotherm with a peak at 133 0C.

Conclusion: Simple nanocrystallization causes a decrease in the particle size of hydrochlorothiazide but with a disruption in the thermal properties while the inclusion of a surfactant in the nanocrystallization process causes a further decrease in the size and an improvement in the thermal behaviour of the drug.