title: Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: improve dissolution rate and bioavailability.
abstract: The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Changshan
authors.initials: C
authors.lastname: Sun
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address: silingwang@syphu.edu.cn.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002244:Carbon / Q000737:chemistry*; D000068579:Celecoxib; D004337:Drug Carriers / Q000737:chemistry*; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D008297:Male; D009584:Nitrogen / Q000737:chemistry; D016062:Porosity; D011720:Pyrazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D011720:Pyrazoles; D013449:Sulfonamides; D002244:Carbon; D000068579:Celecoxib; D009584:Nitrogen
keywords: Dissolution kinetics; Mesoporous carbon; Needle-like crystallinity; Poorly water soluble drug; Spherical pore