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SUMMARY The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201
studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units
(matrix tablets and osmotic pumps) were administered with different amounts of food in the
stomach, ranging from fasted state to heavy breakfast. Gastric emptying was hiffected by the
nature of the dosage form and the presence of food in the stomach. Solutions and pellets were
emptied even when the stomach was in the digestive mode, while single units were retained for
long periods of time, depending on the size of the meal. In contrast, measured intestinal transit
times were independent of the dosage form and fed state. The small intestinal transit time of
about three hours (mean 1 h SEM) has implications for the design of dosage forms for the
sustained release of drugs in specific positions in the gastrointestinal tract.
ence in the gastrointestinal transit patterns in
digestive and interdigestive states. Based on recent
physiological studies it could be predicted that a
non-disintegrating single unit dosage form would
remain in the stomach until the end of the fed phase
and then be cleared from the stomach and through
to the terminal ileum by the migrating myoelectric
complex."7 Consequently, small intestinal transit
would be expected to be of the order of 15-2 hours,
provided the interdigestive, or non-fed state was
maintained.6 Solutions of drugs, or pellet formulations of a size less than about 2 mm would be
expected to empty from the stomach during the
digestive phase and have similar small intestinal
transit times to those Yeported for meals - about
two to four hours.6 7
Various reports have considered the gastric
emptying of markers foodstuffs and a variety of
dosage forms.7-10 Factors such as particle size,
calorific values of meals, specific effects of fats,
posture, stress etc, have been well described.
Detailed studies on the transit from stomach to
ileocaecal junction are fewer in number, however.6
Read7 has commented recently that for the most
part gastric emptying and small bowel transit are
independent variables, each being controlled by its
own regulatory mechanisms.
Address for correspondence: Professor S S Davis, Department of Pharmacy,
Several methods are available to measure small
University of Nottingham, University Park, Nottingham.
intestine transit times.6 These include radiography,
Received for publication 4 November 1985.
intubation techniques, metabolisable markers (hyd886
887
888
Table Details of pharmaceutical formulations, subjects, and fed states
Study
Formulation
Si
S2
S3
S4
Solution-DTPA
Solution-DTPA
Solution-DPTA
Solution-DPTA
P1
P2
P3
P4
PS
P6
P7
P8
P9
P1O
P11
P12
P13
P14
Pellets
Pellets-resin
Pellets-resin
Pellets-resin
Pellets
Pellets-coated
Pellets-coated
Pellets
Pellets
Pellets
Pellets
Pellets
Pellets-coated
Pellets
Ti
T2
T3
T4
TS
T6
T7
T8
T9
T10
Tll
T12
T13
T14
T15
T16
T17
Size
(mm)
Subjects
Label
M-5
M-6
M-6
M-6
99mTc
0-31-2
0-S1-8
0-51-8
0-51-8
0-81-2
0-7-1-0
0-7-1-0
0-7-1-0
0-6-08
0-81-2
0-6-08
0-81-2
0-7-1-0
0-7-1-0
M-4
M-6
F-5D
F-SC
M-6
M-8
M-4
M-6
M-8
M-6
M-8
M-6
M-4
M-6
99mTc
17x4
25x9
25x9
17x4
24x7
25x9
2-5 diam.
12-0 diam.
24x7
17x4
17x4
10-5
8-0 diam.
8-0 diam.
12-0 diam.
17x4
24x7
M-6
M-6
F-SD
F-6
M-4
F-SC
M-4
M-8
M-6
F-6
M-6
M-6
M-6
M-4
M-8
M-4
M-6
6
6
99WTC
99mTc
99mTc
"'In
"'In
"'In
99mTc
99mTc
99mTc
99mTc
99mTc
99mTc
99mTc
"'In
99mIn
99mTc
"'In
99mTc
99mTc
"'In
"'In
99mTc
"'In
"'In
"'In
"'In
99MT
"'lIn
"'1In
"'lIn
"'lIn
"'In
99MTc
131
Drug
present
Fed
state
No
No
Yes
Yes
LB
LB
LB
LB
No
No
No
No
No
No
No
No
No
Yes
No
Yes
No
No
FA
FA
FA
FA
VA
LB
LB
LB
LB
LB
HB
HB
HB
HB
Yes
No
No
Yes
No
No
Yes
No
No
Yes
Yes
Yes
No
No
No
No
No
FA
FA
FA
FA
FA
FA
LB
LB
LB
LB
LB
LB
VA
HB
HB
HB
HB
No
No
SM
SM
M-male, F-female, D-diarrhoea, C-constipation, FA-fasted, LB-light breakfast (-1500 kJ), HB-heavy breakfast (-3600 U),
VA-variable meal, SM-standard meal (800 kJ).
previously. 7
18 20
889
GASTRIC EMPTYING
Solution
11I
Gastric empty ng
Pellets
*I
*I
I>12
I
~~ ~~~0
1~~~~~~
1~~~~~
Fil
0
0
.3
00
I
I
I
I
I
00
I
I
I
i
~~~~0
I
I
I
I00
1
I
I
I
I
0 1~~~
I
I
I
_
21
I*
G6
31
I
_
*7
! ! ! i0
I
I~~~~~~
Mecils
101
91
Single unit
I
I
I
CM
I=
00
I
00
0
Ti
T7
T17
P7
P11
P1
Fl
P3
P5
P13
T3
S3
P9
T5
T9
T13
Tll
T15
S1
P2 P4 P6 P8 P10 P12 P14
T2 T4 T6 T8 T10 T12 T14 T16
52 54
fF2
Fig. 1 Gastric emptying ofpharmaceutical dosage forms. Individual data points as filled circles. MeanSEM.
I.000
890
Small intestine transit
Meals
Single unit
Pellets
Solution
9
8
0
Itj
GP
*Lw
.0
a10.1
0~~~~~~
21
I*
\
i~~~~~
**
S1
4.
Fl
F2
0L
-4
Solution
I
hmlmld.
Pellets
Single unit
891
892
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doi: 10.1136/gut.27.8.886
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Notes