Particle-Size-Determined Crystallization and Dissolution Behavior of Amorphous Griseofulvin

Amorphous active pharmaceutical ingredients (APIs) are generally considered to have significantly higher bioavailability, compared to their crystalline counterpart, due to the enhanced solubility of the disordered phase. However, an akin functionality can be also adopted by the particle size of the powdered API. In this case study, a detailed investigation of the particle-size-influenced properties of amorphous griseofulvin powders will be introduced.

The crystallization of amorphous griseofulvin powders in the range 20 - 1000 μm (+ 2 - 10 μm only for crystalline form) was studied calorimetrically, spectroscopically, and microscopically. Dissolution profiles of pharmaceutical tablets with incorporated either amorphous or crystalline griseofulvin were obtained under conditions simulating the path through the gastrointestinal tract.

Standard crystal growth regime was accompanied by the rapid diffusionless growth mode, which was detected at low heating rates for the finest griseofulvin powders. The dissolution profiles of the pharmaceutical tablets with incorporated individual griseofulvin powder fractions were described in terms of the Korsmeyer-Peppas model (indicating the release by super case II transport).

Particle size was found to play dominant role in the dissolution kinetics, whereas the difference in the dissolution rates of the crystalline and amorphous particles was rather negligible. This is a beneficial finding, considering the very low stability of finely powdered amorphous griseofulvin, but at the same time, it negates the primary purpose of amorphization. Main benefit is thus that of the coarse amorphous griseofulvin powder, which can be utilized to fine-tune the dissolution profile due to its delayed dissolution.