Understanding gastric forces calculated from high-resolution pill tracking.
Although other methods exist for monitoring gastrointestinal motility and contractility, this study exclusively provides direct and quantitative measurements of the forces experienced by an orally ingested pill. We report motive forces and torques calculated from real-time, in vivo measurements of the movement of a magnetic pill in the stomachs of fasted and fed humans. Three-dimensional net force and two-dimensional net torque vectors as a function of time data during gastric residence are evaluated using instantaneous translational and rotational position data. Additionally, the net force calculations described can be applied to high-resolution pill tracking acquired by any modality. The fraction of time pills experience ranges of forces and torques are analyzed and correlate with the physiological phases of gastric digestion. We also report the maximum forces and torques experienced in vivo by pills as a quantitative measure of the amount of force pills experience during the muscular contractions leading to gastric emptying. Results calculated from human data are compared with small and large animal models with a translational research focus. The reported magnitude and direction of gastric forces experienced by pills in healthy stomachs serves as a baseline for comparison with pathophysiological states. Of clinical significance, the directionality associated with force vector data may be useful in determining the muscle groups associated with gastrointestinal dysmotility. Additionally, the quantitative comparison between human and animal models improves insight into comparative gastric contractility that will aid rational pill design and provide a quantitative framework for interpreting gastroretentive oral formulation test results.
Laulicht
Bryan
B
Department of Molecular Pharmacology, Division of Engineering and Medical Science, Brown University, Providence, RI 02912, USA.
Tripathi
Anubhav
A
Schlageter
Vincent
V
Kucera
Pavel
P
Mathiowitz
Edith
E
D000818:Animals; D004285:Dogs; D004435:Eating; D004576:Electromyography; D005215:Fasting; D006801:Humans; D021621:Imaging, Three-Dimensional; D051381:Rats; D013270:Stomach / Q000502:physiology*; D019415:Torque
Am J Physiol. 1992 Aug;263(2 Pt 1):G230-9
1514635
Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G876-82
16293656
Drug Dev Ind Pharm. 2004;30(10):1019-28
15595568
Adv Drug Deliv Rev. 2005 Jun 15;57(8):1210-22
15935870
J Control Release. 2006 Jul 20;113(3):208-15
16806558
Int J Pharm. 2001 Oct 9;228(1-2):209-17
11576783
Neurogastroenterol Motil. 2009 Aug;21(8):838-e57
19400925
Lab Chip. 2006 Jan;6(1):39-45
16372067
J Pharm Pharmacol. 1985 Feb;37(2):91-5
2858556
Neurogastroenterol Motil. 2005 Feb;17(1):148-54
15670274
Gastroenterology. 1996 Mar;110(3):740-7
8608883
Dig Dis Sci. 1994 Dec;39(12 Suppl):14S-17S
7995207
Gastroenterology. 2009 May;136(5):1526-43
19293005
J Control Release. 2006 Mar 10;111(1-2):1-18
16403588
Drug Discov Today. 2005 Feb 15;10(4):249-57
15708743
Int J Pharm. 2000 Nov 4;208(1-2):61-70
11064212
J Clin Pharmacol. 1991 Oct;31(10):968-73
1761729
Neurogastroenterol Motil. 2006 Jun;18(6):472-8
16700727
Neurogastroenterol Motil. 1996 Dec;8(4):277-97
8959733
World J Gastroenterol. 2007 Mar 7;13(9):1365-71
17457967
Eur J Pharm Biopharm. 2010 Jan;74(1):84-92
19602377
J Pharm Sci. 1997 Nov;86(11):1218-22
9383729
J Control Release. 2009 Mar 4;134(2):103-10
19087887
Phys Med Biol. 2000 Oct;45(10):3081-93
11049189