title: Development of a gastric retentive system as a sustained-release formulation of pranlukast hydrate and its subsequent in vivo verification in human studies.
abstract: Pranlukast hydrate was demonstrated in a human site-of-absorption study to have extremely poor absorption properties in the lower gastrointestinal tract. The ratios of AUC0-24 in the distal small bowel and colon compared to stomach delivery were approximately 1/7 and 1/70, respectively. As a consequence, a gastroretentive double-layered tablet formulation (gastric swelling system; GSS), consisting of a swelling layer and a drug release layer, was developed for once-daily dosing. To study the gastric retention of the optimized GSS, an in vivo gamma scintigraphic study was carried out in nine healthy volunteers. The transit profiles demonstrated that the GSS was retained in the stomach for more than 10h. The plasma profile was prolonged, especially following administration after an evening meal. The human data validated the design concept and suggest that GSS could be a promising approach for the development of sustained-release formulation for drugs with a limited absorption window in the upper small bowel.
authors: ONO Pharmaceutical Co., Ltd., Laboratory of Pharmaceutical Development, 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan; Gifu Pharmaceutical University, Laboratory of Pharmaceutical Engineering, Department of Drug Delivery Technology and Sciences, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors: Hikaru
authors: H
authors: Sugihara
authors: ONO Pharmaceutical Co., Ltd., Laboratory of Pharmaceutical Development, 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors: Yuji
authors: Y
authors: Matsui
authors: Gifu Pharmaceutical University, Laboratory of Pharmaceutical Engineering, Department of Drug Delivery Technology and Sciences, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors: Hirofumi
authors: H
authors: Takeuchi
authors: Quotient Clinical, Mere Way, Ruddington, Nottingham NG11 6JS, UK.
authors: Ian
authors: I
authors: Wilding
authors: Quotient Clinical, Mere Way, Ruddington, Nottingham NG11 6JS, UK.
authors: Alyson
authors: A
authors: Connor
authors: ONO Pharmaceutical Co., Ltd., Laboratory of Pharmaceutical Development, 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors: Kazuya
authors: K
authors: Abe
authors: ONO Pharmaceutical Co., Ltd., Laboratory of Pharmaceutical Development, 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan. Electronic address: nishiura@ono.co.jp.
authors: Akio
authors: A
authors: Nishiura
mesh_terms: D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002867:Chromones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005753:Gastric Mucosa / Q000378:metabolism*; D005772:Gastrointestinal Transit; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D002867:Chromones; D003692:Delayed-Action Preparations; C047681:pranlukast
keywords: Gastric retention; Human gamma scintigraphy; Sustained-release; Swelling