Chemistry Reference
In-Depth Information
TABLE 6.1. Recommended Biorelevant Media Compositions [11,25,26,28
30]
-
FeSSGF
a
Media Component
Units
FaSSGF-V2
FaSSIF-V2
FeSSIF-V2
Sodium taurocholate
mmol/l
0.08
3
10
Lecithin
mmol/l
0.02
0.2
2
Pepsin
mg/ml
0.1
Glyceryl monooleate
mmol/l
5
Sodium oleate
mmol/l
0.8
Pancreatin
U/l
100
Acetic acid
mmol/l
17.2
Maleic acid
mmol/l
19.2
55.02
Sodium hydroxide
mmol/l
34.8
81.65
Sodium acetate
mmol/l
29.75
Sodium chloride
mmol/l
68
237.02
68.62
125.5
pH
1.6
5
6.5
5.8
Surface tension
mN/m
42.6
Buffer capacity
mmol/
Δ
pH
25
10
25
Osmolality
mOsmol/kg
400
180
390
FaSSGF: fasted-state simulated gastric fluid; FeSSGF: fed-state simulated gastric fluid; FaSSIF: fasted-state
simulated intestinal fluid; FeSSIF: fed-state simulated intestinal fluid.
a
Mixed 1:1 with temperature-treated milk.
human bioperformance as the end target for drug development, but as highlighted in a
recent review by Reppas et al. [26], animal GI physiology can be signi
cantly different
and species-appropriate models should be considered for toxicology formulations or
when developing formulations for animal health purposes.
Another important consideration when conducting biorelevant solubility and disso-
lution studies is to mimic the
fluid dynamics of the GI tract. Biopharmaceutical
Classi
cation System (BCS) class I and III drugs (see Table 6.2 for an overview of
the BCS [31,32]) are soluble drugs at their projected doses, and hence dissolution
experiments are not as sensitive to physiologically relevant sink or hydrodynamics.
For BCS class II drugs, where solubility and dissolution are rate limiting for absorption
and also where high permeability may create an
in vivo
sink, special attention to the
volumes and hydrodynamics of the dissolution test is required. The fasted and fed
volumes in the human small intestine have been determined by magnetic resonance
imaging to be 45
-
319 and 20
-
156 ml, respectively [25]. To create sink for a BCS class II
TABLE 6.2. The Biopharmaceutical Classi
cation System [31,32]
Class I
Class II
Class III
Class IV
High solubility
Low solubility
High solubility
Low solubility
High permeability
High permeability
Low permeability
Low permeability
Generally well
absorbed
Generally poorly
absorbed
High-solubility drugs have dose/solubility ratio
>
250 across pH 1-8; high-permeability drugs have perme-
ability
>
20
×
10
6
cm/s in Caco-2 cell model.
Solubility/dissolution-
limited absorption
Permeability limited
absorption
