Cryo-crystallization under a partial anti-solvent environment as a facile technology for dry powder inhalation development

Industrial research in the field of dry powder inhalation (DPI) technology is still confined to the micronization of active pharmaceutical ingredients (APIs). Earlier studies have identified triboelectric charge as the main reason for the reduced efficiency of most of the marketed formulations. The physical instability of the micronized product aggravates the situation. Direct conversion of an API into an inhalable dry crystal, without applying an attritional force, would be a solution for many issues such as loss of crystallinity or metal contamination of the final product. In this work, Isoniazid (INH) (an anti-TB drug) was converted to inhalable particles using cryo-crystallization under a partial anti-solvent environment. The crystals were dried using a lyophilization technique and furthermore, the powder was characterized. PXRD studies showed that a new polymorph was evolved by the proposed technique. Since lyophilization is a closed method, microbial contamination can also be avoided through this method. Accelerated stability studies at 40 °C with 75% relative humidity indicated that the newly formed crystals had similar stability to that of the raw material (the API).