title: Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.
abstract: The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms.
authors.affiliation: Formulation Technology Research Laboratories, DAIICHI SANKYO Co, Ltd, 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan. shinichiro.tajiri.kr@daiichisankyo.co.jp
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tajiri
authors.forename: Taro
authors.initials: T
authors.lastname: Kanamaru
authors.forename: Makoto
authors.initials: M
authors.lastname: Kamada
authors.forename: Kamada
authors.initials: K
authors.lastname: Makoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Konno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakagami
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D004304:Dosage Forms; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D011812:Quinuclidines / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004304:Dosage Forms; D011812:Quinuclidines; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013876:Thiophenes; C059240:cevimeline