title: Design of transparent film-forming hydrogels of tolterodine and their effects on stratum corneum.
abstract: A transparent film-forming hydrogel formulation for tolterodine was developed using ternary phase diagram and Box-Behnken design (BBD). Carbopol 980 (neutralized by triethanolamine), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC) and Tween 80 were used as matrices. Solvent was the mixture of water and ethyl alcohol. The measured 24 h cumulative drug release rate (86.02%) was consistent with the predicted value (85.42%) in mice. Steady-state flux (J) of tolterodine in optimized formulation across rat full skin, epidermal, dermis and subcutaneous tissue were 15.83, 18.55, 37.15 and 81.82 μg cm(-2) h(-1), respectively. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) results suggested that the hydrogels could impact lipid status in SC, which was consistent with Ea (8.638 kcal/mol) of tolterodine from optimized formulation in rats. In the pharmacokinetic studies, sustained-release over 24 h and absolute bioavailability of the hydrogels (24.53%) was higher than tolterodine tablets (15.16%) in rats. The hydrogels were suitable for systemic administration of tolterodine for the treatment of overactive bladder.
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Dai
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China.
authors.forename: Lengsheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China. Electronic address: sunfengying@jlu.edu.cn.
authors.forename: Fengying
authors.initials: F
authors.lastname: Sun
authors.affiliation: Room 352, Life Sciences Building, School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin 130012, China. Electronic address: liyouxin@jlu.edu.cn.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003408:Cresols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D015195:Drug Design; D065546:Drug Liberation; D005260:Female; D020100:Hydrogels / Q000737:chemistry*; D008815:Mice, Inbred Strains; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D044367:Phase Transition; D010665:Phenylpropanolamine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014018:Tissue Distribution; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D004337:Drug Carriers; D020100:Hydrogels; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate
keywords: Box-Behnken design; Film-forming; Hydrogels; Pharamcokinetics; Tolterodine