Penn State mechanical engineers, working with medical and pharmaceutical researchers, have developed the first computer-generated ‘virtual stomach’ to follow the path of extended-release tablets that are designed to remain in the stomach for hours while slowly releasing medicine.
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’ is said to have shown that tablet motion and mixing are highly sensitive to the pill’s location in the stomach and to the co-ordination between the stomach’s contractions and the opening and closing of the valve leading to the intestines.
‘We can simulate the tablet breaking down with our new approach, watch the slow release of medication happen in a computer movie and analyse the process,’ said Dr. James G. Brasseur, professor of mechanical engineering and leader of the project. ‘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 virtual stomach is said to combine a 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 colourful, 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 analyse the specific processes that lead to release and mixing of medicines from pills in the stomach.
For example, Dr. Anupam Pal, researcher and first author of the Penn team’s research, 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.
Pal 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.
Dr. Anupam Pal presented the team’s results, which was supported by AstraZeneca Pharmaceuticals, at the meeting of the European Society of Neurogastroenterology and Motility in Tubingen, Germany on October 4th.