title: Preparation of a push-pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core-shell structure.
abstract: The purpose of this study was to use mesoporous silica nanoparticles to improve drug dissolution after releasing from a push-pull osmotic pump. Felodipine was selected as the model drug and it was first incorporated into mesoporous silica nanoparticles prepared previously by the solvent evaporation method after we had examined a series of drug-silica ratios to load the drug into the mesoporous silica nanoparticles in order to find the optimum ratio for drug loading. Then, the drug-carrier was added to the drug-layer of the push-pull osmotic pump. PEO (Mw 100,000) was used as a suspending agent and PEO (Mw 6,000,000) was used as an expanding agent. The core tablets were coated with cellulose acetate (CA) as a semipermeable membrane containing polyethylene glycol (PEG) 6000 to control the membrane permeability. In vitro dissolution studies showed that the self-made osmotic pump tablets were able to deliver felodipine in an approximately zero-order manner in 12 h. A pharmacokinetic study was carried out to compare the new system with reference sustained-release tablets. It was found that the half-life of felodipine in the push-pull osmotic pump tablets was prolonged 1.8-fold, the bioavailability was increased 18% and the maximum plasma concentration reduced by 25%. In conclusion, using the self-made push-pull osmotic pump in combination with mesoporous silica nanoparticles was able to effectively increase the bioavailability of felodipine and reduce fluctuations in its plasma concentration.
authors.affiliation: Pharmacy School, Liaoning Medical University, Jinzhou, Liaoning 121001, China. Electronic address: chaoyu0118@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Pharmacy School, Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Zongzhe
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Pharmacy School, Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Pharmacy School, Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Pharmacy School, Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry; D015736:Felodipine / Q000737:chemistry*; D006207:Half-Life; D053758:Nanoparticles / Q000737:chemistry*; D009995:Osmosis; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013607:Tablets / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D015736:Felodipine
keywords: Core–shell structure; Felodipine; Mesoporous silica nanoparticles; Poorly water-soluble drug; Push–pull osmotic pump