title: Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.
abstract: This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lin
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: He
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D001578:Benzopyrans / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D006244:Hardness; D047028:Macrocyclic Compounds / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011208:Powders; D011422:Propionates / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013997:Time Factors; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*; D000099246:Cucurbit(n)urils
chemical_list: D001578:Benzopyrans; D047028:Macrocyclic Compounds; D011208:Powders; D011422:Propionates; D013607:Tablets; D047392:beta-Cyclodextrins; D000099246:Cucurbit(n)urils; C043940:pyranoprofen; C031215:betadex