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<strong>Gastric</strong> <strong>Digestion</strong> <strong>of</strong><br />

<strong><strong>Food</strong>s—Challenges</strong><br />

<strong>and</strong> <strong>Opportunities</strong> <strong>for</strong><br />

<strong>Food</strong> Engineers<br />

R. Paul Singh<br />

Pr<strong>of</strong>essor <strong>of</strong> <strong>Food</strong> Engineering<br />

University <strong>of</strong> Cali<strong>for</strong>nia, Davis<br />

http://www.healinglightseries.com/tutorialdigestion.html


• Introduction<br />

Outline<br />

– Stomach structure, gastric juice, peristalsis<br />

– <strong>Food</strong> <strong>and</strong> drug disintegration <strong>and</strong> stomach emptying<br />

• <strong>Gastric</strong> digestion—disintegration <strong>of</strong> solid foods<br />

– Development <strong>of</strong> a model stomach system<br />

– In vitro studies on food disintegration<br />

• Computational modeling <strong>of</strong> flow in human<br />

stomach


<strong>Digestion</strong> system<br />

• The overall function<br />

– extract nutrients into<br />

useable <strong>for</strong>m<br />

– absorb nutrients<br />

– eliminate unneeded<br />

materials<br />

• <strong>Food</strong> takes between 24-36<br />

hours to pass through the<br />

gastrointestinal tract


Stomach<br />

• Volume: 50ml to 4 liters <strong>of</strong> liquid<br />

• From an engineering perspective, the human<br />

stomach is a receptacle, a grinder, a mixer <strong>and</strong> a<br />

pump that controls the digestion process<br />

– Chemical digestion by enzyme activity<br />

– Mechanical digestion by the mixing in the stomach<br />

• <strong>Gastric</strong> juice: Colorless fluid<br />

– 1.5 L secreted/d<br />

• Hydrochloric acid<br />

– breaks the food apart <strong>and</strong> kills most <strong>of</strong> the bacteria<br />

that you swallow<br />

• Mucus (~1.5 g/L)<br />

– <strong>for</strong>ms a gelatinous coating over the mucosal surface.<br />

• Pepsin (~ 1 g/L)<br />

– proteins broken down into smaller polypeptide chains<br />

• Salt, <strong>Gastric</strong> Lipase<br />

– fat digestion begins here


Antrum<br />

• Pylorus: contracts to empty<br />

materials from the stomach<br />

into the small intestine.<br />

• Pyloric sphincter: a<br />

specialized valve that<br />

selectively empties the small<br />

particles <strong>and</strong> retains the large<br />

• Fundus: begins digestion<br />

<strong>of</strong> proteins <strong>and</strong> mixes<br />

together stomach<br />

contents.<br />

• Body: digests proteins<br />

<strong>and</strong> blends materials in<br />

stomach <strong>and</strong> reduced to<br />

a paste<br />

• Antrum: Breaks down<br />

large food material in to<br />

small particles


Dynamic MRI image series showing propagating antral contraction waves (small<br />

arrows) displayed in time intervals <strong>of</strong> 10 s. (Schwizer <strong>and</strong> others 2006)


Antral contraction <strong>of</strong> stomach<br />

Propulsion, grinding, <strong>and</strong><br />

retropulsion <strong>of</strong> solids by peristaltic<br />

contractions <strong>of</strong> distal stomach<br />

(Kelly 1980)


Dilution <strong>of</strong> food bolus by elution<br />

Color-coded dilution maps acquired at different times after a volunteer ingested<br />

500 ml <strong>of</strong> viscous locust bean gum meal. A transverse EPI image is also shown<br />

as an anatomic road map (L, left; R, right) (Marciani <strong>and</strong> others 2001a)


Measurement <strong>of</strong> stomach <strong>for</strong>ce<br />

Author Force value Methods<br />

Vassallo et<br />

al. 1992<br />

Kamba et<br />

al. 2000<br />

Marciani et<br />

al. 2001b<br />

The <strong>for</strong>ce per<br />

contraction averaged<br />

0.2 N<br />

1.50 N <strong>for</strong> fasting<br />

conditions <strong>and</strong> 1.89 N<br />

<strong>for</strong> fed conditions<br />

0.65 N exerted by the<br />

antral walls<br />

Vassallo MJ, et al. 1992.<br />

a 1.8 cm balloon mounted on a tube <strong>and</strong> fixed a few<br />

centimeters from the antrum <strong>of</strong> a human stomach<br />

a press-coated tablet contained a marker drug with<br />

brittle Teflon outer layer featured by a range <strong>of</strong><br />

fracture strengths.<br />

agar gel beads (diameter 1.27 cm). MRI to directly<br />

image the breakdown <strong>of</strong> the agar gel beads in the<br />

antrum<br />

Marciani et al.<br />

2001b


Manometric tube <strong>and</strong> axial <strong>for</strong>ce catheter used by Marciani et al (2000)


In vivo methods to assess gastric<br />

disintegration <strong>and</strong> emptying rate<br />

• Feeding study<br />

– acquiring the digesta samples using naso-gastric<br />

• Intubation techniques: gastric barostat <strong>and</strong> intraluminal<br />

manometry<br />

– “gold st<strong>and</strong>ards” <strong>for</strong> assessing motility <strong>of</strong> the stomach<br />

• Scintigraphic imaging: liquid barium sulphate, radioopaque<br />

spheres<br />

– st<strong>and</strong>ard method to measure gastric emptying<br />

• Ultrasonography measures gastric volume or antral crosssection.<br />

The in<strong>for</strong>mation is used to estimate the rate <strong>of</strong> emptying<br />

<strong>and</strong> evaluate antral motility.<br />

• Magnetic resonance imaging (MRI)<br />

• Indirect methods such as blood test <strong>and</strong> breath test


Scintigraphic<br />

images show<br />

capsule<br />

disintegration <strong>and</strong><br />

gastric emptying <strong>of</strong><br />

its contents<br />

www.bio-images.co.uk/AAPS2002.pdf


MRI images showing disintegration <strong>and</strong><br />

gastric emptying <strong>of</strong> drug tablet<br />

MRI<br />

www.pharmpr<strong>of</strong>iles.co.uk/UserFiles/File/pdf/DepomedPresentation.pdf


Factors affecting stomach emptying<br />

rate<br />

• food caloric content, macronutrients <strong>and</strong> volume<br />

– 2 – 4 kcal/min (8.4–16.8 kJ/min)<br />

• Increasing the viscosity <strong>of</strong> liquid meals delays<br />

gastric emptying <strong>and</strong> increases satiety<br />

• size, density, texture <strong>and</strong> microstructure <strong>of</strong> the<br />

food<br />

• Biological factors<br />

– body posture, physical activity, age, health, gender


TNO intestinal model (TIM)<br />

Stomach<br />

pH electrode<br />

Hollow fiber membranes<br />

simulating the absorption<br />

Intestine<br />

TNO Nutrition <strong>and</strong> <strong>Food</strong><br />

Research (Zeist, The<br />

Netherl<strong>and</strong>s)


Schematic diagram <strong>of</strong> the dynamic in vitro model <strong>of</strong> the stomach <strong>and</strong><br />

small intestine (TIM): (A) gastric compartment, (B) duodenal<br />

compartment (C) jejunal compartment, (D) ileal compartment, (E) glass<br />

jacket, (F) flexible wall, (G) rotary pump, (H) pyloric valve, (I) pH<br />

electrode, (J) secretion pump, (K) pre-filter, (L) hollow fiber membrane,<br />

(M) dialysis system, (N) ileal delivery valve.


The model gut<br />

• The model gut is used<br />

to investigate effect<br />

<strong>of</strong> food structure on<br />

the release <strong>of</strong><br />

allergens<br />

Institute <strong>of</strong> <strong>Food</strong> Research,<br />

Norwich Research Park, Colney,<br />

Norwich NR4 7UA, UK


In Vitro Dissolution Testing <strong>of</strong> Oral<br />

Dosage Forms: USP apparatus<br />

• Apparatus 1 - Basket (37º)<br />

• Apparatus 2 - Paddle (37º)<br />

• Apparatus 3 - Reciprocating Cylinder (37º)<br />

• Apparatus 4 - Flow-Through Cell (37º)<br />

• 500 ml –1000 ml (900 ml)<br />

• Agitation speed: 50-100 rpm <strong>for</strong> basket method, <strong>and</strong> 25-75 rpm <strong>for</strong><br />

paddle method.<br />

• Aqueous dissolution medium composed <strong>of</strong> 0.1 N HCl (or pH 1.2)


Research Needs<br />

• Influence <strong>of</strong> hydrodynamic <strong>and</strong> mechanical <strong>for</strong>ces<br />

present in stomach on food disintegration<br />

• Changes in rheological properties <strong>of</strong> gastric juice<br />

<strong>and</strong> the hydrodynamics <strong>of</strong> the fluid with ingested<br />

meal <strong>and</strong> their implications on food digestion.<br />

• In vitro digestion models developed <strong>for</strong> detailed<br />

investigations to determine rate <strong>of</strong> food<br />

disintegration<br />

• Role <strong>of</strong> food material properties such as texture<br />

<strong>and</strong> microstructure on kinetics <strong>of</strong> food<br />

disintegration in gastric environment


Objectives<br />

• Gain an underst<strong>and</strong>ing <strong>of</strong> the link between food<br />

material properties obtained at the manufacturing<br />

stage <strong>and</strong> the disintegration kinetics <strong>of</strong> the food<br />

in the human stomach.<br />

– Develop an in vitro stomach model <strong>for</strong> detailed<br />

investigations <strong>of</strong> food disintegration kinetics<br />

– Explore the relationships between food material<br />

properties including texture <strong>and</strong> microstructure <strong>and</strong> the<br />

disintegration kinetics <strong>of</strong> food products<br />

• Develop a computational model <strong>of</strong> fluid flow <strong>and</strong><br />

solid disintegration in a human stomach


Model stomach system<br />

• Custom-built turntable<br />

• Jacketed glass chamber<br />

• On-line Force measuring apparatus<br />

Sample holder


Force (N)<br />

0.25<br />

0.2<br />

0.15<br />

0.1<br />

0.05<br />

0<br />

Pr<strong>of</strong>ile <strong>of</strong> continuous <strong>for</strong>ce <strong>and</strong><br />

0 1 2 3 4 5<br />

Time (min)<br />

periodic <strong>for</strong>ce<br />

Force (N)<br />

0.35<br />

0.28<br />

0.21<br />

0.14<br />

0.07<br />

Vassallo MJ, et al. 1992.<br />

0<br />

0 5 10<br />

Time (min)


Hardness (N)<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

0 3 6 9 12<br />

Cooking Soaking time time (min)<br />

Hardness <strong>of</strong> raw <strong>and</strong> cooked<br />

carrot samples during soaking<br />

in gastric juice<br />

Hardness (N)<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

Carrot hardness during<br />

cooking in boiling water<br />

0 10 20 30 40 50<br />

Soaking time (min)<br />

Raw carrots<br />

2-min-cooked<br />

carrots<br />

6-min-cooked<br />

carrots


Wt/W0<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0 50 100<br />

Time (min)<br />

Raw carrot,<br />

0.015 N<br />

2-min-cooked<br />

carrot, 0.017N<br />

6-min-cooked<br />

carrot, 0.017N<br />

Mass retention curve<br />

<strong>for</strong> raw <strong>and</strong> cooked<br />

carrots<br />

Emptying data with fitting <strong>of</strong> curves<br />

by power exponential model<br />

y(<br />

t)<br />

= 1−<br />

( 1<br />

−<br />

e<br />

−kt<br />

β<br />

)<br />

y(t): the fractional meal retention, β >1.0<br />

indicates an initial delay in emptying, β<br />


Mass retention data <strong>of</strong> carrots fitted<br />

with modified power exponential model<br />

Wt/W0<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0.1<br />

0 20 40 60 80<br />

Time (min)<br />

0.012 N<br />

0.070 N<br />

0.18 N<br />

0.24 N<br />

Raw carrots<br />

• Factors influencing mass<br />

retention curve<br />

– hardness <strong>of</strong> the foods during<br />

digestion<br />

– <strong>and</strong> the extent <strong>of</strong> physical<br />

<strong>for</strong>ce acting on the foods<br />

Wt/W0<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

Wt/W0<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0 20 40 60<br />

Time (min)<br />

2 min-cooked carrots<br />

0 10 20 30 40<br />

Time (min)<br />

6 min-cooked carrots<br />

0.017 N<br />

0.02 N<br />

0.103 N<br />

0.146 N<br />

0.006 N<br />

0.017 N<br />

0.03 N<br />

0.041 N


Exponential relationship between half<br />

time (t 1/2 ) <strong>and</strong> mechanical <strong>for</strong>ce (F)<br />

t1/2<br />

70<br />

60<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

Raw carrots 2-min-cooked carrots 6-min-cooked carrots<br />

Raw carrots:<br />

y = 60.821e -5.3434x R 2 = 0.9646<br />

2-min-cooked carrots:<br />

y = 40.501e -9.6003x R 2 = 0.8424<br />

6-min-cooked carrots:<br />

y = 25.326e -30.34x R 2 = 0.817<br />

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35<br />

Force (N)


Competition between surface erosion <strong>and</strong><br />

tenderization during food disintegration<br />

<strong>Food</strong><br />

particulate<br />

during<br />

digestion<br />

a)<br />

b)<br />

Tenderization front S<strong>of</strong>t layer<br />

Wt/W0<br />

Wt/W0<br />

1<br />

0.2<br />

1<br />

0.2<br />

0 5 10 15<br />

Time (min)<br />

0 20 40 60<br />

Time (min)


Wt/W0<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0 10 20 30 40 50<br />

Time (min)<br />

Hardness <strong>of</strong> ham sample during<br />

soaking in gastric juice<br />

0.013 N<br />

0.023 N<br />

0.075 N<br />

0.14 N<br />

Hardness (N)<br />

6<br />

5<br />

4<br />

3<br />

2<br />

Mass retention data <strong>of</strong><br />

ham fitted with model<br />

0 20 40 60 80<br />

Soaking time (min)


Penetration front<br />

Carrot (Methylene blue)


Penetration front: microscopy images<br />

<strong>of</strong> carrot during digestion


Influence <strong>of</strong> sample size <strong>of</strong> carrots on half-time <strong>for</strong> disintegration<br />

Half time (t1/2)<br />

70<br />

60<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

y = 58.202e -5.7505x<br />

R 2 = 0.8854<br />

y = 40.948e -10.876x<br />

R 2 = 0.8227<br />

0 0.1 0.2 0.3<br />

Force (N)<br />

Small size (d 3mm<br />

× L 4.5mm)<br />

Big size (d 6mm × L<br />

6mm)


Wt/W0<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0 20 40 60 80 100<br />

Disintegration time (min)<br />

37˚C optimal<br />

temperature <strong>for</strong><br />

digestion<br />

Half time t1/2 (min)<br />

21 C<br />

29 C<br />

37 C<br />

45 C<br />

200<br />

160<br />

120<br />

80<br />

40<br />

0<br />

Disintegration rate <strong>of</strong><br />

carrots with<br />

temperature <strong>of</strong> gastric<br />

juice (0.14 N)<br />

20 30 40 50<br />

Temperature <strong>of</strong> gastric juice (°C)


Wt/W0<br />

Disintegration rate <strong>of</strong> carrots<br />

decreases with increase in<br />

the viscosity <strong>of</strong> gastric juice<br />

1<br />

0.8<br />

0.6<br />

0.4<br />

0 20 40 60 80<br />

Disintegration time (min)<br />

1% gum<br />

0.5% gum<br />

0.25%gum<br />

no gum<br />

<strong>Gastric</strong> emptying curves<br />

<strong>for</strong> the 4 locust bean<br />

gum meals: lowviscosity<br />

nonnutrient<br />

control (LVC), highviscosity<br />

nonnutrient<br />

control (HVC), lowviscosity<br />

nutrient (LVN),<br />

<strong>and</strong> high-viscosity<br />

nutrient (HVN).<br />

(Marciani et al. 2001a)


Wt/W0<br />

1.2<br />

1.1<br />

1<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0 50 100 150 200 250<br />

Disintegration time (min)<br />

Almond<br />

Wt/W0<br />

1.2<br />

1<br />

0.8<br />

0.6<br />

0.4<br />

raw<br />

fried<br />

roasted<br />

Peanut<br />

0 50 100 150 200 250<br />

Time (min)<br />

Roasting <strong>and</strong> frying increase disintegration<br />

rates <strong>of</strong> peanut <strong>and</strong> almond (0.1 N)<br />

raw<br />

fried<br />

roasted


1 mm<br />

Changes in structure <strong>of</strong><br />

almond during digestion (30<br />

min) static<br />

100 um


Needs in Pharmaceutical research<br />

• “... mechanical functions <strong>of</strong> stomach <strong>and</strong><br />

duodenum are well defined in terms <strong>of</strong><br />

viscoelastic properties, movement patterns <strong>of</strong><br />

their walls….flow phenomenon to digestion<br />

remains to be established…contribution <strong>of</strong><br />

pressure <strong>for</strong>ces, shear stresses, flow reversals<br />

<strong>and</strong> vortical flow remains to be quantified.”<br />

Schulze (2006)


Computational Model <strong>of</strong> a Human<br />

Stomach<br />

(a) Stomach geometry constructed with circular rings, (b) Tetrahedral grids<br />

used to mesh half <strong>of</strong> the stomach geometry


Grids <strong>of</strong> Stomach geometry modified in FLUENT using user defined functions


Conclusions<br />

• The custom-built model stomach system is useful <strong>for</strong><br />

studying the kinetics <strong>of</strong> food disintegration in the<br />

stomach<br />

• Kinetics <strong>of</strong> food disintegration is mainly affected by<br />

surface erosion <strong>and</strong> texture s<strong>of</strong>tening during digestion<br />

• Half-time (t 1/2 ) is an important parameter describing the<br />

ability <strong>of</strong> foods to resist disintegration during digestion<br />

– Higher mechanical <strong>for</strong>ce, smaller size, <strong>and</strong> longer cooking time<br />

are all related with shorter half-time<br />

• Stomach emptying pr<strong>of</strong>ile might be largely affected by<br />

the food disintegration process<br />

– related to the changes in food texture <strong>and</strong> the <strong>for</strong>ces acting on<br />

the foods during the digestion process.<br />

• <strong>Food</strong> processing steps such as boiling, roasting <strong>and</strong><br />

frying appear to improve solid disintegration rates

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