Formation of Paliperidone Cocrystals as Multi-Component Systems for the Functionality Enhancement

[摘要] The aim of the present investigation was to prepare paliperidone-PHBA (PAL-PHBA), paliperidone-saccharin sodium (PAL-SS) cocrystals for improved physico-mechanical properties. The paliperidone cocrystals prepared by solvent evaporation technique were fully characterized by employing melting point, aqueous solubility, dissolution, Fourier Transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry(DSC), Powder X-Ray Diffraction (PXRD) , and Scanning Electron Microscopy (SEM) techniques.Six formulations of orodispersible tablets of selected paliperidone cocrystals were prepared using Croscarmellose Sodium (CCS), Sodium Starch Glycolate (SSG), and Crospovidone (CP) as superdisintegrants. The prepared batches were evaluated for hardness, friability, weight uniformity, content uniformity, in vitro dispersion time,andin vitro drug release.Based on the results, formation of cocrystals was confirmed. Pharmaceutical behaviors in terms of solubility, dissolution, and tabletability suggested superior functionality of cocrystals. The formulations F-III and F-VI (containing CP) were identified as better formulations among the formulations developed by PAL-SS and PAL-PHBA cocrystals, respectively. Further, it could be reasonably expected that the obtained formulationmayresult in an increase in its bioavailability, with the possibility of reducing drug dosage and side effects.The concept of cocrystallizationwas successfulfor preparing paliperidone cocrystals with improved physico-mechanical properties. The aim of the present investigation was to prepare paliperidone-PHBA (PAL-PHBA), paliperidone-saccharin sodium (PAL-SS) cocrystals for improved physico-mechanical properties. The paliperidone cocrystals prepared by solvent evaporation technique were fully characterized by employing melting point, aqueous solubility, dissolution, Fourier Transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry(DSC), Powder X-Ray Diffraction (PXRD) , and Scanning Electron Microscopy (SEM) techniques.Six formulations of orodispersible tablets of selected paliperidone cocrystals were prepared using Croscarmellose Sodium (CCS), Sodium Starch Glycolate (SSG), and Crospovidone (CP) as superdisintegrants. The prepared batches were evaluated for hardness, friability, weight uniformity, content uniformity, in vitro dispersion time,andin vitro drug release.Based on the results, formation of cocrystals was confirmed. Pharmaceutical behaviors in terms of solubility, dissolution, and tabletability suggested superior functionality of cocrystals. The formulations F-III and F-VI (containing CP) were identified as better formulations among the formulations developed by PAL-SS and PAL-PHBA cocrystals, respectively. Further, it could be reasonably expected that the obtained formulationmayresult in an increase in its bioavailability, with the possibility of reducing drug dosage and side effects.The concept of cocrystallizationwas successfulfor preparing paliperidone cocrystals with improved physico-mechanical properties.

[学科分类] 药学、药理学、毒理学（综合）

[关键词] Paliperidone;Cocrystals;Solvent evaporation;Orodispersible tablets;Superdisintegrants;Direct compression.