Table 6.
Examples of variants of physiologically based in vitro procedures (not calibrated) applied to Pb particles (2 pages)
| GENERAL | ORAL | GASTRIC | INTESTINAL | ||||||
|---|---|---|---|---|---|---|---|---|---|
|
References |
Mixing |
Extraction |
Time, pH |
Fluid |
S/L (g.mL-1) |
Time, pH |
Fluid |
Time, pH |
Fluid |
|
Sheppard et al. 1995[116] |
|
Centrifugation, filtration 0.2 μm |
|
|
|
4 h, pH 2.0 |
NaCl; pepsin; HCl |
18 h, pH 7.5 |
NaHCO3; NaCl; bile; pancreatin; α-amylase |
|
Berti and Cunningham 1997[125] |
Stir bar |
|
|
|
1/100 |
1 h, pH 2.5 |
Pepsin; organic acids; HCl |
2 h, pH 7.0 |
NaHCO3; pancreatin; bile |
|
Davis et al. 1997[126] |
Wrist action shaker |
Centrifugation (2,100 g; 25 min) |
|
|
1/10 |
2 h, pH 1.3 |
Pepsin; organic acids; HCl |
2 h, pH 7.0 |
NaHCO3; pancreatin; bile |
|
Hamel et al. 1998[92] |
Shaking water bath |
Centrifugation (1,380 g; 10 min) |
|
|
1/100 to 1/5000 |
2 h |
NaCl; pepsin; HCl |
|
|
|
Hamel et al. 1999[102] |
Water bath, 90 cyc/min |
Centrifugation (906 g; 10 min), filtration 0.45 μm |
5 s, pH 5.5 |
Mucin; urea; KCl; NaCl; Na2HPO4; CaCl2.4H2O |
1/2160 |
2 h |
NaCl; pepsin; HCl |
2 h |
NaHCO3 |
|
Oliver et al. 1999[89] |
Wrist action shaker |
Filtration 0.45 μm |
|
|
1/10 |
2 h, pH 1.3 to 3.0 |
Organic acids; HCl; with(out) pepsin |
16 h, pH 7.0 |
NaHCO3 with(out) bile & pancreatin |
|
Ellickson et al. 2001[57] |
Bath set, 90 cyc/min |
Centrifugation (200 g; 20 min) & (906 g; 15 min); HNO3, 48 h; filtration 0.45 μm |
|
Mucin; urea; CaCl2.H2O; NaCl; KCl; Na2HPO4 |
1/2160 |
2 h, pH 1.4 |
Pepsin; NaCl; HCl |
4 h, pH 6.5 |
NaHCO3 |
|
Oomen et al. 2002, Van De Wiele et al. 2007[82,87]; DIN test |
Agitator, 200 rpm |
Centrifugation (7,000 g; 10 min) |
|
|
1/50 |
2 h, pH 2.0 |
HCl; [pepsin; mucin]* |
6 h, pH 7.5 |
Phosphate buffer; [bile; trypsin; pancreatin]* |
|
Oomen et al. 2002, Van De Wiele et al. 2007[82,87]; SHIME test |
Stirring, 150 rpm |
Centrifugation (7,000 g; 10 min) |
|
|
1/2.5 to 1/40 |
3 h, pH 2.0 (fast) or 4.0 (fed) |
Nutrilon plus; pectin; mucin; cellobiose; proteose peptone; starch; glucose |
5 h, pH 6.5 |
NaHCO3; pancreatin; bile |
|
Oomen et al. 2002, Van De Wiele et al. 2007[82,87]; TIM test |
Peristaltic |
Ultrafiltration |
5 min, pH 5.0 |
|
|
Fast: 40 min, pH 4.5 to 1.8 |
HCl; lipase; pepsin* 0.5 mL/min |
Fast: 5.3 h, pH 6.5 to 7.2 |
NaHCO3; pancreatin; bile* 1 mL/min |
| Fed: 4.5 h, pH 6.5 to 7.2 | |||||||||
| Fed: 1.5 h, pH 5.0 to 2.0 | |||||||||
|
Yu et al. 2006[113] |
Water bath, 90 rpm |
Filtration 0.45 μm |
|
Mucin; urea; KH2PO4; CaCl2.H2O; NaCl, KCl |
1/400 |
2 h, pH 1.4 |
NaCl; pepsin; HCl |
2 h, pH 6.5 |
NaHCO3 |
|
Bruce et al. 2007[94] |
Ar |
Centrifugation (10,000 g; 15 min), filtration 0.22 μm |
|
|
1/100 |
1 h pH 1.3 (fast) to 4 (fed) |
Pepsin; HCl; organic acids |
3 h pH 7.0 |
NaHCO3; bile; pancreatin |
|
Saikat et al. 2007[104] |
|
Centrifugation (2,100 g; 25 min) |
|
|
1/38-1/100 |
1 h pH 1.1 or 2.5 |
Pepsin; organic acids; HCl |
4 h, pH 5.5 or 7.0 |
NaHCO3; pancreatin; bile |
|
Triantafyllidou et al. 2007[26] |
Gentle mixing |
No separation |
|
|
1/16,667 |
3 h, pH 1.2 |
NaCl; pepsin; HCl |
|
|
|
Turner and Ip 2007[127] |
End-over-end |
Centrifugation (2,100 g;10 min) |
|
|
1/200 |
2 h, pH 2.5 |
Pepsin; HCl; Na malate & citrate; lactic & acetic acids |
4 h, pH 7.0 |
NaHCO3; bile; pancreatin |
|
Van De Wiele et al. 2007[87] |
Water rotator set |
Filtration 0.45 μm |
|
|
1/100 |
1 h pH 2.5 |
Pepsin; HCl; Na citrate & malate; lactate, acetate |
4 h, pH 7.0 |
NaHCO3; bile; pancreatin |
|
Bosso and Enzweiler 2008; Bosso et al. 2008[107,114] |
Slow orbital + Ar flux |
Centrifugation (5,000 rpm; 20 min) |
|
|
1/100 |
1 h, pH 1.7 |
Pepsin; HCl; citric, malic, acetic, & lactic acids |
2 h, pH 7.0 |
NaHCO3; bile; pancreatin |
|
Turner et al. 2009[128] |
Constant, lateral |
Centrifugation (2,000 g; 10 min) |
|
|
1/100-1/143 |
1 h, pH 2.5 |
Pepsin; HCl; Na malate, citrate; lactic & acetic acids |
4 h, pH 7.0 |
NaHCO3; bile; pancreatin |
| Sialelli et al. 2010[115] | Orbital, 150 rpm | 1/100 | 1 h, pH 1.5 | Pepsin; HCl; Na citrate; malic & lactic acids | 3.5 h, pH 7.0 | Pancreatin, NaHCO3 | |||