title: Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride.
abstract: Conventional ophthalmic formulations often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of the drug in the precorneal area. To solve those problems, a thermosensitive in situ gelling and mucoadhesive ophthalmic drug delivery system was prepared and evaluated, the system was composed of poloxamer analogs and polycarbophil (PCP) and betaxolol hydrochloride (BH) was selected as model drug. The concentrations of poloxamer 407 (P407) (22% (w/v)) and poloxamer 188 (P188) (3.5% (w/v)) were identified through central composite design-response surface methodology (CCD-RSM). The BH in situ hydrogel (BH-HG) was liquid solution at low temperature and turned to semisolid at eye temperature. BH-HG showed good stability and biocompatibility, which fulfilled the requirements of ocular application. In vitro studies indicated that addition of PCP enhanced the viscosity of BH-HG and the release results of BH from BH-HG demonstrated a sustained release behavior of BH because of the gel dissolution. In vivo pharmacokinetics and pharmacodynamics studies indicated that the BH-HG formulation resulted in an improved bioavailability and a significantly lower intraocular pressure (IOP). The results suggested BH-HG could be potentially used as an in situ gelling system for ophthalmic delivery to enhance the bioavailability and efficacy.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Academy of Medical and Pharmaceutical Sciences of Zhengzhou University, Zhengzhou, HeNan 450052, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Tuanbing
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China. Electronic address: zhaoyx@zzu.edu.cn.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015784:Betaxolol / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D065546:Drug Liberation; D005123:Eye / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D007700:Kinetics; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D012212:Rheology / Q000187:drug effects; D013696:Temperature
chemical_list: D009883:Ophthalmic Solutions; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D015784:Betaxolol
keywords: Betaxolol hydrochloride; In situ hydrogel; Ophthalmic delivery system; Poloxamer; Polycarbophil