title: Mechanism of controlled drug release from a salting-out taste-masking system.
abstract: A "salting-out taste-masking system" is a multiparticulate system consisting of a drug core, a salting-out layer containing salts and water-soluble polymers, and a water-penetration control layer containing water-insoluble materials. The system generates a long lag time for numbness masking, with subsequent immediate drug release for high bioavailability. In this study, sodium carbonate (Na2CO3) and hydroxypropylmethylcellulose (HPMC) were used as the salt and water-soluble polymer in the salting-out layer, respectively. The drug release rate from the formulation containing the HPMC layer was affected by the Na2CO3 concentrations in the media used in the drug dissolution tests. The HPMC layer suppressed drug release in a medium with a high Na2CO3 concentration, and subsequently increased the drug release rate in a medium with a low Na2CO3 concentration. Drug release from the system was suppressed while Na2CO3 remained in the formulations. Microscopic changes in HPMC in the salting-out layers correlated well with changes in the drug release rate. These results indicate that, in the salting-out taste-masking system, the drug release suppression and the immediate release are caused by insolubilization and dissolution of the water-soluble polymer respectively. These findings will allow for smarter formulation design.
authors.affiliation: Drug Delivery, Pharmaceutical Research and Development Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan. takayuki.yoshida@jp.astellas.com
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maeda
authors.forename: Masataka
authors.initials: M
authors.lastname: Katsuma
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000082:Acetaminophen / Q000378:metabolism; D001682:Biological Availability; D002254:Carbonates / Q000378:metabolism*; D016503:Drug Delivery Systems; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012492:Salts / Q000378:metabolism; D012995:Solubility; D013649:Taste; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D002254:Carbonates; D004364:Pharmaceutical Preparations; D012492:Salts; D014867:Water; D000082:Acetaminophen; D065347:Hypromellose Derivatives; C005686:sodium carbonate; D008747:Methylcellulose