title: Bio-relevant dissolution testing of hard capsules prepared from different shell materials using the dynamic open flow through test apparatus.
abstract: Current compendial dissolution and disintegrating testing is unable to mimic physiological conditions affecting gastric drug release from immediate release dosage forms. In order to obtain more realistic data, a novel test setup was developed that we term a 'dynamic open flow through test apparatus'. It is based on the previously described dissolution stress test device and attempts to simulate the intra-gastric dissolution conditions pertinent to immediate release dosage forms administered under fasting conditions with respect to flow rates, intra-gastric temperature profiles and gastric motility. The concept of the dynamic open flow through test apparatus has been tested using five different types of hard capsules: conventional hard gelatin capsules (HGC), three hypromellose based capsules (Vcaps, Vcaps Plus and DRcaps) and pullulan based capsules (Plantcaps). These were of different sizes but all contained 100mg caffeine in each formulation, adjusted to avoid buoyancy by addition of excipient. When the capsules were stressed in the apparatus under the dynamic flow conditions applying mild pressure simulating gastric motility, release from release from Vcaps Plus, Vcaps and Plantcaps capsules was very well comparable to HGC. Capsules are usually swallowed with cold water and the temperature dependency of release from gelatin was noted as a significant factor, since heat exchange in the stomach is slow.
authors.affiliation: University of Greifswald, Institute of Pharmacy, Center of Drug Absorption and Transport, Felix-Hausdorff-Strasse 3, 17487 Greifswald, Germany; Physiolution GmbH, Walter-Rathenau-Strasse 49a, 17489 Greifswald, Germany.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Garbacz
authors.affiliation: Capsugel R&D, 10, rue Timken, 68027 Colmar, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Cadé
authors.affiliation: Capsugel R&D, 10, rue Timken, 68027 Colmar, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Benameur
authors.affiliation: University of Greifswald, Institute of Pharmacy, Center of Drug Absorption and Transport, Felix-Hausdorff-Strasse 3, 17487 Greifswald, Germany. Electronic address: werner.weitschies@uni-greifswald.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
mesh_terms: D000284:Administration, Oral; D001702:Biopharmaceutics / Q000295:instrumentation / Q000379:methods*; D002110:Caffeine / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry*; D005215:Fasting; D005746:Gastric Emptying; D005780:Gelatin / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D006244:Hardness; D006245:Hardness Tests; D006801:Humans; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives / Q000737:chemistry; D007700:Kinetics; D011312:Pressure; D012995:Solubility; D013270:Stomach / Q000502:physiology*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013696:Temperature
chemical_list: D002214:Capsules; D005079:Excipients; D005936:Glucans; D002110:Caffeine; D065347:Hypromellose Derivatives; C009109:pullulan; D005780:Gelatin
keywords: Biorelevant dissolution testing; Dynamic flow through apparatus; Gastric hydrodynamics; Hard capsules; Hypromellose; Pullulan