The researchers note that, although many medications are prepared in extended-release form, the details of exactly how the pills break down and release medicine in the stomach are largely unknown. The new "virtual stomach" has shown that tablet motion and mixing are highly sensitive to the pill's location in the stomach and to the coordination between the stomach's contractions and the opening and closing of the valve leading to the intestines.
Dr. James G. Brasseur, professor of mechanical engineering and leader of the project, says, "We can simulate the tablet breaking down with our new approach, watch the slow release of medication happen in a computer movie and analyze the process. Computer simulation allows us to 'control' the stomach and therefore provides more detail than you could get with human or even animal experiments. In fact, computer simulation may be the only way to observe the stomach's mechanical processes in such fine detail."
The researchers expect the new information provided by the virtual stomach to aid in the design and delivery of new extended-release tablet formulations, to shed light on diseases involving stomach motility and to help explain basic gastric function.
Dr. Anupam Pal will present the team's results at the meeting of the European Society of Neurogastroenterology and Motility in Tubingen, Germany, Oct. 4. Pal is first author of the team's report and a postdoctoral researcher in Brasseur's laboratory. He received the Society's Young Investigator Award for his work on the study. His poster is titled: "Relationship Between Gastric Motility, Mixing and Drug Release, Analyzed Using Computer Simulation."
The other authors, in addition to Brasseur and Pal, are Dr. Bertil Abramhamsson, AstraZeneca Pharmaceuticals, Mölndal, Sweden; Dr. Werner Schwizer, Dept. of Gastroenterology, University Hospital, Zurich, Switzerland; and Dr. Geoffrey S. Hubbard, Dept. of Gastroenterology, The Royal Melbourne Hospital, Australia.
The virtual stomach combines a sophisticated computer program with a realistic stomach geometry model derived from Magnetic Resonance Imaging (MRI) movies of the human stomach. The resulting computer simulations are presented as colorful, cartoon-like movies of the human stomach showing pressures, the motion of gastric fluid, and the path and breakdown of tablets. These computer simulations allow researchers to analyze the specific processes that lead to release and mixing of medicines from pills in the stomach.
For example, Pal measured the shear stresses or the "rubbing" the tablet undergoes from fluids and the walls of the stomach. At the same time, he evaluated the dispersion and mixing of the medication due to the wave-like contractions on the stomach walls. He found that these wave-like motions underlie both the shear stresses that contribute to the breakdown of the tablet and the mixing of the medicine. Pal also found that extended periods of moderate shear stress exist which continuously wear the tablet's surface and lead to gradual dispersal of the medication. At the same time, shorter-acting high stresses can remove large pieces of tablet surface and contribute to uneven wear and uneven dispersal of the medication.
The virtual stomach simulations also revealed that the stomach has three very different zones, one very gentle, one moderately stressful to tablets and conducive to mixing and a third highly active zone where a tablet can break down rapidly and mixing is accelerated. He also found that buoyancy affects longer-time mixing and drug release. AstraZeneca Pharmaceuticals supported the research.