title: A novel pulsatile drug delivery system based on the physiochemical reaction between acrylic copolymer and organic acid: in vitro and in vivo evaluation.
abstract: Multilayer-coating technology is the traditional method to achieve pulsatile drug release with the drawbacks of time consuming, more materials demanding and lack of efficiency. The purpose of this study was to design a novel pulsatile drug delivery system based on the physiochemical interaction between acrylic copolymer and organic acid with relatively simpler formulation and manufacturing process. The Enalapril Maleate (EM) pulsatile release pellets were prepared using extruding granulation, spheronization and fluid-bed coating technology. The ion-exchange experiment, hydration study and determination of glass transition temperature were conducted to explore the related drug release mechanism. Bioavailability experiment was carried out by administering the pulsatile release pellets to rats compared with marketed rapid release tablets Yisu. An obvious 4h lag time period and rapid drug release was observed from in vitro dissolution profiles. The release mechanism was a combination of both disassociated and undisassociated forms of succinic acid physiochemically interacting with Eudragit RS. The AUC0-τ of the EM pulsatile pellets and the market tablets was 702.384 ± 96.89 1 hn g/mL and 810.817 ± 67.712 h ng/mL, while the relative bioavailability was 86.62%. These studies demonstrate this novel pulsatile release concept may be a promising strategy for oral pulsatile delivery system.
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Xing
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Yangtze River Pharmaceutical Group, State Key Laboratory for Advanced Formulation Technologies, Taizhou, PR China. Electronic address: zhenghongwu66@cpu.edu.cn.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004656:Enalapril / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D008297:Male; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013607:Tablets; D013997:Time Factors; D044366:Transition Temperature
chemical_list: D000180:Acrylic Resins; D000806:Angiotensin-Converting Enzyme Inhibitors; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013607:Tablets; C050528:Eudragit RS; D004656:Enalapril
keywords: Acrylic copolymer; Enalapril Maleate; Film coating; Organic acid; Pulsatile pellets