PREPARATION AND CHARACTERIZATION OF SMARTCRYSTALS FOR DISSOLUTION ENHANCEMENT OF POORLY WATER -SOLUBLE NIFLUMIC ACID

Abstract

Nanonization is commonly applied to overcome the challenge of low solubility and dissolution improving the bioavailability of poorly water-soluble drugs. In this study, nanocrystals of niflumic acid (NIF) were produced by bead pre-milling followed by high-pressure homogenization (HPH) to enhance the dissolution rate of NIF. Different drying procedures were applied to elucidate the effect of drying processes on the re-dispersibility of drug nanocrystals, including drying at room temperature, vacuum drying, and freeze-drying using mannitol or trehalose as a cryoprotectant. NIF nanosuspensions were checked for the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP). The dry nanocrystals were characterized by their MPS, thermal and structural manner, solubility, and dissolution. After 40 min of pre-milling and 30 min of HPH, NIF nanosuspension showed MPS and PDI of 240 nm and 0.29, respectively. The drying procedure showed a significant impact on the MPS after re-dispersion in water. Simple drying and vacuum drying produced nanocrystals of 813.5 and 560.6 nm, respectively. However, mannitol and trehalose-based dried nanocrystals showed MPS of 406.55 and 276.55 nm, respectively. DSC thermograms and XRPD diffractograms confirmed the crystallinity of NIF. The smartcrystals showed a complete NIF release from the freeze-dried particles with trehalose at pH 7.4, whereas, at pH 5.6, a maximum of 20% of drug release was obtained from the freeze-dried particle with mannitol. The raw NIF showed less than 5% release in the both media. The enhancement of the dissolution rate of NIF would increase its onset of action, reduce the required dose, and minimize its gastrointestinal side effects, resulting in an efficient delivery system.