title: Controlled gastric emptying. 1. Effects of physical properties on gastric residence times of nondisintegrating geometric shapes in beagle dogs.
abstract: The importance of three physical parameters (size, shape, and flexibility) on gastric retention in fasting dogs was examined to assess the feasibility of designing a dosage form to achieve a consistent and predictable residence in the stomach. Test shapes were molded from Silastic elastomer or made from extruded polyethylene or polyethylene blends and included 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with test shapes administered in gelatin capsules. Gastric retention was monitored by X ray over a 24-hr period. Six shapes (ring, tetrahedron, cloverleaf, disk, string, and pellet) were screened in vivo for their gastric retention potential. The tetrahedrons (each leg 2 cm in length) exhibited 91-100% retention at 24 hr. The rings (3.6-cm diameter) provided 100% retention at 24 hr. Rings and tetrahedrons of varying flexural moduli were prepared by blending low-density polyethylene and ethylene:vinyl acetate copolymer. A positive correlation existed between flexural modulus and gastric retention. The results indicate that it is feasible to design a platform for a dosage form that can be administered to beagle dogs in capsule form and be retained for 24 hr.
authors.affiliation: INTERx-Merck Sharp & Dohme Research Laboratories, Lawrence, Kansas 60046.
authors.forename: R
authors.initials: R
authors.lastname: Cargill
authors.forename: L J
authors.initials: LJ
authors.lastname: Caldwell
authors.forename: K
authors.initials: K
authors.lastname: Engle
authors.forename: J A
authors.initials: JA
authors.lastname: Fix
authors.forename: P A
authors.initials: PA
authors.lastname: Porter
authors.forename: C R
authors.initials: CR
authors.lastname: Gardner
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004285:Dogs; D005260:Female; D005746:Gastric Emptying; D008297:Male; D010316:Particle Size