title: A two-step strategy to design high bioavailable controlled-release nimodipine tablets: the push-pull osmotic pump in combination with the micronization/solid dispersion techniques.
abstract: In order to decrease the fluctuation of blood concentration and to increase the oral bioavailability of nimodipine (NMD), a two-step strategy including the push-pull osmotic pump (PPOP) method in combination with micronization and solid dispersion techniques, was used to prepare the controlled-release high-bioavailability solid dosages. The optimization of formulation and process was conducted by comparing effects of different solubilization methods on release behavior of NMD. The in vitro dissolution studies indicated that both the two strategies were able to deliver NMD in the predetermined zero-order manner from 2 to 12h, regardless of effects of release media and agitation rates. Although the Cmax values of two PPOP tablets were lower than that of the reference formulation, both the Tmax values were prolonged, demonstrating the prominent controlled release performance. In comparison with the commercial reference tables, the relative bioavailability of the two formulations was 67.0% and 121.1%, respectively, indicating the solid dispersion technique was more efficient than the micronization technique in terms of solubilization capability and absorption enhancement. In summary, the two-step strategy, combining the push-pull osmotic pump method with the solid dispersion technique, is a very effective method to prepare high bioavailable controlled-release formulations of the poorly soluble drugs, i.e. NMD, taking into account the therapeutical efficiency and safety.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China; Shanxi Provincial People's Hospital, No. 29, Shuangta Street, Taiyuan, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Chai
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Physical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: xulu1974@hotmail.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China; Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China. Electronic address: sunjin66@21cn.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D009553:Nimodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009995:Osmosis; D012995:Solubility; D013607:Tablets; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D013607:Tablets; D009553:Nimodipine
keywords: A two-step strategy; Bioavailability; Micronization; Nimodipine; Push–pull osmotic pump; Solid dispersion