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

Abstract

Industrial research in the field of dry powder inhalation (DPI) technology is still confined to micronization of active pharmaceutical ingredient (API). Earlier studies have identified triboelectric charge as the main reason for the reduced efficiency of most of the marketed formulations. Physical instability of the micronized product aggravates the situation. Direct conversion of API into inhalable dry crystal, without applying attritional force, will be a solution for many issues such as loss of crystallinity and metal contamination of the final product. In this work, Isoniazid (INH) (an anti-TB drug) was converted to inhalable particles through cryo-crystallization under partial anti-solvent environment.Crystals were dried using lyophilization technique and further, 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 o C with 75% relative humidity indicated that the newly formed crystals had similar stability as that of the raw material (API).