title: Development of pressure-sensitive dosage forms with a core liquefying at body temperature.
abstract: Pressure-sensitive dosage forms have been developed that are intended for pulsatile delivery of drugs to the proximal small intestine. The novel dosage forms are composed of insoluble shell and either a hard fat W32 or polyethylene glycol (PEG) 1000 core that are both liquidizing at body temperature. The release is triggered by predominant pressure waves such as contractions of the pylorus causing rupture of the shell and an immediate emptying of the liquefied filling containing the active ingredient. In consequence immediately after the trigger has been effective the total amount of the drug is intended to be available for absorption in the upper small intestine. Both core types were coated with a cellulose acetate film that creates a pressure-sensitive shell in which mechanical resistance is depending on the coating thickness. Results of the texture analysis confirmed a correlation between the polymer load of the coating and the mechanical resistance. The dissolution test performed under conditions of physiological meaningful mechanical stress showed that the drug release is triggered by pressure waves of ⩾300 mbar which are representing the maximal pressure occurring during the gastric emptying.
authors.affiliation: University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wilde
authors.affiliation: University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Bock
authors.affiliation: University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany.
authors.forename: Marieke
authors.initials: M
authors.lastname: Wolf
authors.affiliation: University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Glöckl
authors.affiliation: Physiolution GmbH, Greifswald, Germany.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Garbacz
authors.affiliation: University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany. Electronic address: werner.weitschies@uni-greifswald.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
mesh_terms: D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004304:Dosage Forms; D008863:Microspheres; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry*; D011312:Pressure; D012995:Solubility / Q000187:drug effects; D013314:Stress, Mechanical; D014280:Triglycerides / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D004304:Dosage Forms; D014677:Pharmaceutical Vehicles; D014280:Triglycerides; C009683:witepsol
keywords: Dissolution stress test; Drug-targeting; Gastric emptying; Liquid core formulation; Pressure-sensitive; Pylorus