title: Salting-out taste-masking system generates lag time with subsequent immediate release.
abstract: Salting-out effects were utilized for developing a multiparticulate system balancing numbness masking and high bioavailability. A "salting-out taste-masking system" consisting of a drug core containing acetaminophen as a model drug, a salting-out layer containing sodium carbonate (Na(2)CO(3)) and hydroxypropylmethylcellulose (HPMC), and a water-penetration-control layer consisting of cetanol was designed and prepared. The system successfully generated a long lag time while achieving immediate drug release. In the system, the Na(2)CO(3) release rate was slower and the lag time was longer than when the water-penetration-control layer was not present. During the release of Na(2)CO(3) from the system, the release of HPMC and drug was suppressed. These results indicated that the water-penetration-control layer maintained a high concentration of Na(2)CO(3), prevented HPMC's dissolution, and generated a long lag time of drug release. The system generated longer lag time and released drug more immediately than formulation containing the water-penetration-control layer of same thickness without the salting-out layers. These results indicated the salting-out layers were necessary for obtain a long lag time and subsequent immediate drug release. This novel taste-masking system has the potential to be a useful multiparticulate dosage form for effective, safe, and user-friendly drug therapy.
authors.affiliation: Drug Delivery, Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan. takayuki.yoshida@jp.astellas.com
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Tasaki
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Katsuma
authors.forename: K
authors.initials: K
authors.lastname: Sako
authors.forename: T
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000082:Acetaminophen / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D002254:Carbonates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005233:Fatty Alcohols / Q000737:chemistry; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012492:Salts; D012995:Solubility; D013649:Taste; D013997:Time Factors
chemical_list: D002254:Carbonates; D005233:Fatty Alcohols; D004364:Pharmaceutical Preparations; D012492:Salts; D000082:Acetaminophen; D065347:Hypromellose Derivatives; C005686:sodium carbonate; D008747:Methylcellulose; C005031:cetyl alcohol