How to proceed with easily recrystallizing secnidazole in designing polyelectrolyte complex-based films for periodontitis treatment?

Secnidazole is a second generation 5-nitroimidazole with high potential for application in anaerobic periodontal infections therapy. In this study, the process of developing the drug-loaded films composed of oppositely charged chitosan and pectin for intra-pocket administration is presented. Due to limitations of layer-by-layer technique in receiving systems of this type, which resulted from spontaneous crystallization of secnidazole at the stage of drying, a new preparation method was developed. For this purpose, drug cocrystallization technique as well as two-step drying procedure were implemented in order to minimize secnidazole crystals growth during solvent evaporation. Through visual assessment, mechanical strength measurements and scanning electron microscopy imaging, the most promising secnidazole-chitosan cocrystals-loaded films were selected for further physicochemical (via differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction, optical microscopy) and pharmaceutical (in vitro release, antimicrobial and swelling tests) analyses. The impact of utilized polymeric composition and polyelectrolyte complex structures as well as secnidazole form (crystalline/amorphous) on the films performance was observed. The increased temperature of drying enhanced secnidazole-polymers miscibility, which resulted in desirable drug loading improvement and also significantly prolonged secnidazole release to the artificial saliva.