title: Investigations of bisacodyl with modified β-cyclodextrins: Characterization, molecular modeling, and effect of PEG.
abstract: Bisacodyl inclusion into hydroxypropyl-β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.
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: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Peixiao
authors.initials: P
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001726:Bisacodyl / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002400:Cathartics / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D005769:Gastrointestinal Motility / Q000187:drug effects; D054368:Laxatives / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002400:Cathartics; D004337:Drug Carriers; D054368:Laxatives; D047392:beta-Cyclodextrins; D001726:Bisacodyl; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin
keywords: 2,6-di-O-Methyl-β-cyclodextrin (PubChem CID: 10171019); Bisacodyl; Bisacodyl (PubChem CID: 2391); Characterization; D(2)O (PubChem CID: 24602); DMSO-d(6) (PubChem CID: 75151); Diphenoxylate (PubChem CID: 13505); Hydroxypropyl-β-cyclodextrin (PubChem CID: 14049689); Isothermal titration calorimetry; Methanol (PubChem CID: 887); Modified β-cyclodextrins; Molecular modeling; Polyethylene glycol; Polyethylene glycol (PubChem CID: 5327147)