Bio-relevant dissolution testing of hard capsules prepared from different shell materials using the dynamic open flow through test apparatus

Eur J Pharm Sci. 2014 Jun 16:57:264-72. doi: 10.1016/j.ejps.2013.08.039. Epub 2013 Sep 8.

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.

Keywords: Biorelevant dissolution testing; Dynamic flow through apparatus; Gastric hydrodynamics; Hard capsules; Hypromellose; Pullulan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Biopharmaceutics / instrumentation
  • Biopharmaceutics / methods*
  • Caffeine / administration & dosage
  • Caffeine / chemistry
  • Capsules
  • Chemistry, Pharmaceutical
  • Equipment Design
  • Excipients / chemistry*
  • Fasting
  • Gastric Emptying*
  • Gelatin / chemistry
  • Glucans / chemistry
  • Hardness
  • Hardness Tests
  • Humans
  • Hydrogen-Ion Concentration
  • Hypromellose Derivatives / chemistry
  • Kinetics
  • Pressure
  • Solubility
  • Stomach / physiology*
  • Technology, Pharmaceutical / instrumentation
  • Technology, Pharmaceutical / methods*
  • Temperature

Substances

  • Capsules
  • Excipients
  • Glucans
  • Caffeine
  • Hypromellose Derivatives
  • pullulan
  • Gelatin