Apparatus for simulating the effect of the living organism on the change in shape, the disintegration and dissolution behaviour and the active-ingredient release of a pharmaceutical dosage form

An apparatus for simulating the effect of a living organism on the change in shape, the disintegration and dissolution behaviour and the active-ingredient release of a pharmaceutical dosage form, including a beaker-shaped container for accommodating a test medium and the pharmaceutical dosage form and an agitating device for agitating the test medium, which agitating device can be moved periodically in a reciprocating movement into and back out of the container, wherein the agitating device includes a piston-shaped head portion arranged on a piston rod, which head portion is provided with through-openings for the test medium and the distance of the piston-shaped head portion from the container floor can be altered periodically in accordance with the periodic reciprocating movement of the agitating device, wherein, the piston rod is suspended from a gallows-shaped boom or the piston rod passes through a bore in the gallows-shaped boom in such a manner that downward movement of the piston-shaped head portion arranged on the piston rod is caused by gravity alone and wherein there is arranged in the container an intermediate base supported on the container floor, the base being provided with through-openings for the test medium and serving as a support for the dosage form, wherein the distance between the intermediate base and the container floor is adjustable by a device for adjusting the distance between the base and the floor.

CROSS-REFERENCE TO RELATED APPLICATIONS 
This is a 371 of PCT/EP 94/02485, filed Jul. 28, 1994. 
BACKGROUND OF THE INVENTION 
The invention relates to an apparatus for simulating the effect of the 
living organism on the change in shape, the disintegration and dissolution 
behaviour and the active-ingredient release of a pharmaceutical dosage 
form according to the preamble of patent claim 1. 
Pharmaceutical dosage forms must be adapted to the physiological conditions 
prevailing on or in the living organism, for example on the skin or in the 
gastrointestinal tract, in order to be as well suited as possible to the 
living organism, for example as regards their rate of dissolution and the 
release of active ingredients. For that purpose, recommended analysis 
procedures that reproduce as closely as possible the real physiological 
conditions of the living organism and are intended to allow comparison of 
the different dosage forms have often been laid down by government bodies. 
Various analysis apparatuses that take those procedures into account and 
that are intended to simulate and reproduce the physiological, i.e. 
including the physico-chemical, conditions of, for example, the 
gastrointestinal tract are known. For the determination of the 
disintegration and dissolution behaviour of solid oral dosage forms, for 
example tablets, dragees and capsules, in the gastrointestinal tract, 
analysis apparatuses have been developed that, especially, permit analyses 
in accordance with the "United States Pharmacopoeia XXII, 1990" (USP). 
One such analysis apparatus that conforms to the USP (USP XXII, 1990, pages 
1577-1583) is based on the wire-basket method proposed in the USP. The 
test arrangement comprises a cylindrical vessel of transparent material, 
for example glass or plexiglass, having a hemispherical base. Arranged 
inside the vessel is a wire basket secured to a shaft rotatable by a 
motor. The shaft and the wire basket secured thereto are vertically 
displaceable, so that the distance between the base of the wire basket and 
the floor of the vessel is adjustable. In order to analyse the 
disintegration and dissolution behaviour of an oral dosage form, the 
latter is arranged inside the cage and is lowered together with the cage 
into the vessel which contains, for example, synthetic gastric or 
intestinal fluid. The shaft and with it the cage is then rotated by the 
motor at the speed specified in the test procedure. The rotation of the 
cage together with the dosage form contained therein is intended to 
simulate the shearing forces of the fluid acting on the dosage form in the 
gastrointestinal tract. The gastric or intestinal fluid in the vessel can 
be pumped round continuously in order to allow the active-ingredient 
concentration to be determined continuously using an associated analysis 
unit, for example a spectroscopic analysis unit. In that manner the 
release of active ingredient by the dosage form in the gastric or 
intestinal fluid over time can be determined. Because the vessel is 
transparent, the disintegration of the solid dosage form can be determined 
visually in accordance with certain predetermined criteria. In particular, 
the condition of the dosage form is visually assessed periodically over 
relatively long periods of time. 
A further known analysis apparatus is based on the paddle method proposed 
in the USP (USP XXII, 1990, pages 1577-1583). As in the case of the 
apparatus described hereinbefore, that analysis apparatus comprises a 
cylindrical vessel of preferably transparent material and having a 
hemispherical base. A motor-driven shaft is provided at one end with 
paddles that are immersed into the gastric or intestinal fluid in the 
vessel. The shaft is again vertically displaceable to enable the distance 
between the paddles and the floor of the vessel to be adjusted in 
accordance with the specifications. In order to be tested, the dosage form 
is introduced into the fluid. If necessary, the solid dosage form can be 
weighted with a piece of inert material to prevent it from floating up. 
The rotation of the paddles agitates the fluid and is intended to simulate 
the shearing forces of the fluid acting on the dosage form in the 
gastrointestinal tract. As in the analysis apparatus mentioned 
hereinbefore, the gastric or intestinal fluid in the vessel can be pumped 
round continuously in order to allow the active-ingredient concentration 
to be determined continuously using an associated analysis unit, for 
example a spectroscopic analysis unit, and thus to establish the 
active-ingredient-release curve of the dosage form over time or, as 
already mentioned above, the disintegration of the dosage form can be 
observed visually. 
In an article in the International Journal of Pharmaceutics, 95 (1993), 
67-75, 1993, Elsevier Science Publishers B.V., it is proposed that, for 
improved simulation of the physiological conditions in the 
gastrointestinal tract, an analysis apparatus based on the paddle method 
be adapted by adding a number of small polystyrene beads to the gastric or 
intestinal fluid in the vessel. The polystyrene beads have a diameter of 
6.35 mm. In the tests described, up to 4000 beads were added. It is 
claimed that in the experiments relatively good agreement was found 
between the results measured and results obtained in animal experiments. 
A brochure from SOTAX AG, 4008 Basle, Switzerland, describes a SOTAX 
tablet-disintegration testing apparatus which allows the disintegration 
ability of tablets, capsules or dragee cores to be determined in a manner 
that conforms to the USP. The testing apparatus comprises a number of test 
tubes of transparent material (glass, plexiglass) which are open at the 
top and closed off at the bottom by a wire mesh. A number of test tubes 
are gathered together in a basket frame that is suspended by its central 
shaft from a gallows-shaped lifting device. The basket frame containing 
the test tubes is immersed into a cylindrical vessel containing, for 
example, gastric or intestinal fluid that can be arranged in a 
temperature-controlled heating bath. The lifting device is connected by a 
rod to a motor-driven eccentric device arranged inside a housing. By way 
of the rod the rotation of the eccentric device is converted into a 
vertical reciprocating movement of the basket frame. In that known 
apparatus the physiological behaviour of the gastrointestinal tract is 
simulated by the controlled reciprocating movement of the basket frame 
containing the test tubes. The immersion of the solid dosage forms lying 
on the wire mesh closing off the bottom ends of the tubes can be 
controlled at the same time. It is also possible to vary the immersion 
frequency, which is customarily fixed. That allows the more or less 
periodic emergence and floating to the surface of the dosage form that 
take place in the gastrointestinal tract to be approximated. The test to 
determine the disintegration behaviour is again carried out, for example, 
visually in accordance with specific prescribed disintegration criteria 
that vary according to the dosage form. The dissolution behaviour and the 
active-ingredient release can again be determined, for example by means of 
spectroscopy, using a further analysis unit attached to the apparatus. 
Although the action of the shearing forces of the test fluid on the dosage 
form to be tested can be approximated relatively well using those known 
analysis apparatuses and the results measured also correlate relatively 
well with, for example, results obtained by means of animal experiments, 
the known apparatuses nevertheless exhibit a number of disadvantages 
worthy of improvement. As is known, more or less frequent contractions 
take place in the gastrointestinal tract. In the stomach, and to a lesser 
extent also in the intestine, dosage forms are subjected not only to the 
shearing forces of the fluid but also to pressure and kneading processes 
by the walls of the stomach and/or of the intestine and/or to pressure 
waves in the gastric and/or intestinal fluid. Those pressure and kneading 
processes have a not inconsiderable effect on the rate of dissolution of a 
dosage form. It is those very pressure and kneading processes, for example 
in the gastrointestinal tract, that cannot be simulated by the known 
analysis apparatuses. The attempt to simulate such processes by the 
addition of a plurality of small beads seems after all rather far removed 
from the real conditions. The behaviour of novel dosage forms, such as 
active-ingredient releasing sachets that expand in the body, can be 
characterised only with difficulty, and even then not completely, using 
known analysis apparatuses. In particular, it is desirable also to 
investigate the change in their shape and volume in the gastrointestinal 
tract. Furthermore, there is a general desire for a test apparatus capable 
of simulating the effects of pressure and kneading on a pharmaceutical 
dosage form outside the body, for example on transdermal systems, 
intrauterine implants or suppositories, ophthalmological implants and 
inlays, or in veterinary medicine. 
The problem underlying the present invention is therefore to mitigate those 
disadvantages of the analysis apparatuses of the prior art. An analysis 
apparatus is to be provided which allows both the shearing forces of the 
fluid and the pressure and kneading effects of the living organism, not 
solely, but especially, in the gastrointestinal tract, to be simulated. In 
addition, the analysis apparatus is to provide the preconditions for 
characterising dosage forms automatically on the basis of their changes in 
shape and volume. 
SUMMARY OF THE INVENTION 
All those and other, associated problems are solved by an apparatus for 
simulating the effect of the living organism on the change in shape, the 
disintegration and dissolution behaviour and the active-ingredient release 
of a pharmaceutical dosage form, having the characterising features of 
patent claim 1. The invention provides especially an apparatus for 
simulating the effect of the living organism, for example of the 
gastrointestinal tract, on the change in shape, the disintegration and 
dissolution behaviour and the active-ingredient release of a 
pharmaceutical dosage form, which comprises a beaker-shaped container for 
accommodating a test medium, for example a synthetic gastric or intestinal 
fluid, and a pharmaceutical dosage form, and an agitating device, 
suspended from a gallows-shaped boom, for the test medium. The agitating 
device can be moved periodically into and back out of the beaker, 
preferably vertically. The vertically reciprocating agitating device 
comprises a piston-shaped head portion arranged on a piston rod, which 
head portion is provided with through-openings for the test medium and the 
distance of which from the container floor can be altered periodically in 
accordance with the periodic reciprocating movement of the agitating 
device. Thus by moving the agitating device up and down, on the one hand 
the flow conditions of the test medium in the gastrointestinal tract can 
be obtained and, on the other, at the same time the contractions thereof 
caused by peristalsis and the resulting pressure and kneading effects on 
the pharmaceutical dosage form can be simulated. 
The gallows-shaped boom is preferably connected by way of a rod to a 
motorised eccentric device, a crank shaft or the like, in such a manner 
that the rotary movement of the eccentric device can be converted into a 
periodic vertical reciprocating movement of the gallows-shaped boom. The 
periodicity of the lifting movement is thus ensured and very easily 
regulated. 
Because the frequency of the vertical reciprocating movement can be 
regulated and can be adjusted, for example, from zero strokes per minute 
to as many as 60 strokes per minute, different regions of the 
gastrointestinal tract can be simulated very well. It is also possible in 
that manner to reproduce the different activity of the gastrointestinal 
region at different times of the day, for example during sleeping and 
waking phases. 
In an especially preferred variant of the test apparatus, the test 
apparatus is equipped with a preferably pneumatic lifting device which 
allows the gallows-shaped boom to be raised so that, regardless of the 
particular position of the eccentric device, the agitating device is 
raised and exerts no pressure on the dosage form. Thus periods of complete 
rest, for example of the gastrointestinal tract, can be reproduced. It is, 
of course, also possible to ensure that the agitating device permanently 
exerts an adjustable pressure on the dosage form in order thus to simulate 
the permanent pressure of the living organism on the dosage form. The mass 
of the piston rod and of the head portion is preferably adjustable so that 
the pressure that the head portion exerts if it comes to rest on the 
dosage form is from approximately 5 mN/cm.sup.2 to approximately 500 
N/cm.sup.2. The activity of different areas of the gastrointestinal region 
can thus be simulated even more accurately. 
Because an intermediate base provided with through-openings for the test 
medium is arranged in the container and acts as a support for the dosage 
form, and because the distance between the intermediate base and the floor 
of the container is adjustable, the requisite length of stroke, and hence 
the speed of movement of the agitating device, can be altered. 
An especially wide range of potential uses for the apparatus that are 
especially applicable to the problem of the invention is created by 
suspending the piston rod connected to the head portion from the 
gallows-shaped boom in such a manner that it is vertically displaceable 
relative thereto. In that arrangement, the piston rod preferably passes 
freely through a bore in the gallows-shaped boom in such a manner that its 
downward movement is caused by gravity alone and is braked by the 
gallows-shaped boom. The fact that the piston rod passes freely through 
the bore allows further downward movement of the gallows-shaped boom if 
the head portion comes to rest on the dosage form or the beaker floor or 
the intermediate base. In addition, the piston rod is provided at its end 
remote from the head portion with an abutment in such a manner that it is 
carried along during the upward movement of the gallows-shaped boom. If 
the piston rod is also connected to a length meter that consists, for 
example, of a thread attached to the back end of the piston rod and 
connected to a sliding potentiometer, the vertical displacement of the 
piston rod relative to the gallows-shaped boom can be measured very 
easily. 
In order to characterise the change in shape of a dosage form, it is 
advantageous if at least the piston-shaped head portion is shaped in such 
a manner that when it comes to rest on the dosage form it touches the 
peripheral edges thereof. If the length meter, for example the 
potentiometer, is connected to a computer unit, the measured lengths of 
displacement of the piston rod relative to the gallows-shaped boom can be 
converted into changes in volume, width or thickness of a dosage form 
disintegrating and/or being dissolved in the test medium. For example, in 
that manner the increase in volume of an expanding dosage form can be 
determined very accurately. 
Because the piston-shaped head portion can be rotated about the piston rod, 
which acts as an axle, during its reciprocating movement, the agitation of 
the fluid can be improved further. It is especially advantageous if the 
piston rod is provided on its periphery with a thread and the 
gallows-shaped boom has a threaded bore through which the piston rod 
passes in such a manner that during the reciprocating movement of the 
gallows-shaped boom the piston rod rotates until the abutment arranged at 
the end of the piston rod remote from the head portion rests against the 
boom. 
In order to have the option of keeping the test medium at a desired or 
prescribed temperature, which as far as possible corresponds to the 
temperature in the particular part of the body to be simulated, the 
beaker-shaped container is preferably arranged in a temperature-controlled 
heating bath. 
In order to prevent possible evaporation of the test medium at elevated 
temperatures, for example at temperatures of from approximately 32.degree. 
C. to approximately 38.degree. C., the beaker-shaped container is 
preferably equipped with a removable lid having a through-opening for the 
piston rod. 
For carrying out series tests it is advantageous for several, preferably at 
least two, agitating devices to be suspended from a gallows-shaped boom, 
which agitating devices can be moved up and down in a corresponding number 
of beaker-shaped containers containing the test medium and dosage forms 
arranged on the intermediate bases. The capacity of the apparatus can be 
increased further by providing a plurality of gallows-shaped booms having 
agitating devices suspended from them and a number of beaker-shaped 
containers corresponding to the number of agitating devices. Such series 
tests are not limited merely to the disintegration and dissolution 
behaviour of different dosage forms. It is also possible for chemical and 
biological processes that play a role therein to be tested at the same 
time, for example by adding enzymes, salts, acids and the like to the 
various containers. 
The apparatus according to the invention for simulating the physiological 
conditions is used preferably in an analysis system for determining the 
disintegration behaviour and/or the dissolution behaviour and the 
active-ingredient release of pharmaceutical dosage forms. In that system, 
an analysis unit, for example a spectroscopic analysis unit, is connected 
to the simulation apparatus for preferably continuous determination of the 
active-ingredient concentration in a test medium. In that manner it is 
possible for the change in volume or width and/or thickness of a dosage 
form to be determined continuously and for the release of 
active-ingredient, the energy absorption and the progress of chemical or 
biological processes to be detected in parallel therewith. The analysis 
system according to the invention can be used to test and to characterise 
tablets, dragees, capsules, transdermal systems, intrauterine inlays, 
suppositories, ophthalmological inlays or implants, or devices for use in 
veterinary medicine.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
FIG. 1 is a block diagram of an analysis system for testing the 
disintegration and dissolution behaviour and/or the active-ingredient 
release of a preferably solid pharmaceutical dosage form. It has been used 
in the past above all to test dosage forms, such as tablets or dragees. 
Owing to the design of the test apparatuses, those tests had to be limited 
essentially to the effect of the shearing forces of a body fluid in which 
the dosage form was arranged. The analysis apparatus as a whole has the 
reference numeral 1 in FIG. 1. It comprises a test apparatus 2 for the 
pharmaceutical dosage form and an analysis device 4, for example a 
spectrometer, connected thereto. A pump device 3 pumps a test medium, for 
example a body fluid such as gastric or intestinal fluid, from the test 
device 2 via a line 7 to the analysis unit 4. From there, the test medium 
returns via a line 8 to the test apparatus 2. The test apparatus 2 and the 
analysis device 4 are connected via digital 9 and analog 10 data and/or 
control lines to a computer unit 6. An analog amplifier 5 is used to 
amplify the analog signals. Using the computer unit 6, control commands 
can be passed on to the attached devices and the measured data can be 
evaluated. 
The substantial innovation of an analysis system of that type that also 
allows other types of dosage form, for example expanding dosage forms, 
transdermal systems, intrauterine inlays or suppositories, 
ophthalmological implants and inlays, or devices for use in veterinary 
medicine to be characterised, or the effect of the living organism on 
those dosage forms to be tested, consists in the development according to 
the invention of the test apparatus 2. 
FIG. 2 shows a first embodiment of a test apparatus 2 according to the 
invention. It has a beaker-shaped container 21 for accommodating a test 
medium P, for example a synthetic gastric or intestinal fluid, and a 
pharmaceutical dosage form D, and an agitating device 23, suspended from a 
gallows-shaped boom 22, for the test medium P. The agitating device 23 can 
be moved into and back out of the beaker 21 periodically, preferably 
vertically, as indicated by the double arrow V. The vertically 
reciprocating agitating device 23 comprises a piston-shaped head portion 
24 arranged on a piston rod 25 and provided with through-openings 241 
(FIG. 3) for the test medium P; the distance of the head portion from the 
container floor 211 (FIG. 3) can be altered periodically in accordance 
with the periodic reciprocating movement of the agitating device 23. In 
that manner, by reciprocating the agitating device 23, it is possible on 
the one hand to influence the flow conditions of the test medium P and, 
for example, reproduce those of the gastrointestinal tract and on the 
other hand to simulate pressure and kneading influences on the dosage form 
D at the same time. In that manner, for example, the contractions of the 
gastrointestinal tract caused by peristalsis can be reproduced. 
The simulation possibilities are not, however, limited to the 
gastrointestinal tract alone. The fact that the dosage form D can be 
subjected to pressure and kneading action by the agitating device 23 means 
that the effect of other parts of the body, for example on suppositories, 
intrauterine inlays or on ophthalmological implants or inlays can also be 
tested. It is also possible, for example, to track the release of active 
ingredient by a transdermal system under pressure and kneading influences. 
As shown in the drawing, the gallows-shaped boom 22 is connected via a rod 
27 to an eccentric device 28, a crank shaft or the like which is driven by 
an electric motor 29. In that manner the rotary movement of the eccentric 
device 28 is converted into a periodic vertical reciprocating movement V 
of the gallows-shaped boom 22, and hence of the agitating device 23. In 
that manner the periodicity of the lifting movement is ensured, and the 
stroke frequency and the speed of the lifting movement can be very well 
controlled. Part of the boom 22, the rod 27, the eccentric device 28 and 
the drive motor 29, as well as other control and regulating devices that 
may be necessary, are preferably accommodated in a housing 20. 
The frequency of the vertical reciprocating movement V can preferably be 
regulated and is preferably adjustable, for example, from zero strokes per 
minute to as many as 60 strokes per minute. In that manner, for example, 
different regions of the gastrointestinal tract or other regions of the 
living organism can be simulated individually. This also allows the 
different activity of the living organism at different times of the day, 
for example during sleeping and waking phases, to be taken into account. 
It is especially advantageous for the test apparatus 2, as shown in FIG. 2, 
to be equipped with a preferably pneumatic lifting device 41 that allows 
the gallows-shaped boom 22 to be raised. The agitating device 23 can thus 
be raised regardless of the particular position of the eccentric device 
28, with the result that the head portion 24 does not exert any pressure 
on the dosage form D. That enables periods of complete rest, for example 
of the gastrointestinal tract, to be reproduced. Of course the pneumatic 
lifting device 41 can also be constructed in such a manner that the 
agitating device 23 can be pushed down in order thus to exert a permanent, 
preferably adjustable, pressure on the dosage form D. It is thus possible 
to simulate the exertion of permanent pressure of a specific magnitude by 
the living organism on the dosage form D. 
In order to have the option of keeping the test medium P at a desired or 
prescribed temperature that corresponds as far as possible to the 
temperature in the particular part of the body to be simulated, the 
beaker-shaped container 21 is arranged in an outer container 42 (FIG. 3) 
having a temperature-controlled heating bath T (FIG. 3). For that purpose 
that part of the housing 20 that serves as the surface on which the 
temperature-controlled container 42 stands can have a heating plate 
connected to a temperature-control device that monitors the temperature of 
the heating bath T and controls the heat output of the heating plate as 
required. 
FIGS. 3 and 4 show two variants of the test apparatus 2 according to the 
invention that allow an especially wide range of possible uses. In those 
variants the piston rod 25 connected to the head portion 24 is suspended 
from the gallows-shaped boom 22 in such a manner that it is vertically 
displaceable relative thereto, as shown by the double arrow X. In that 
arrangement, the piston rod 25 preferably passes freely through a bore 40 
in the gallows-shaped boom 22 in such a manner that its downward movement 
is caused by gravity alone and is braked by the gallows-shaped boom 22. 
The fact that the piston rod 25 passes freely through the bore 40 allows 
further downward movement of the gallows-shaped boom 22 if the head 
portion 24 comes to rest on the dosage form D, which in the case 
illustrated is an expanding, active-ingredient releasing sachet, or on the 
beaker floor 211. At its end remote from the head portion 24, the piston 
rod 25 is provided with an abutment 30 in such a manner that it is carried 
along during the upward movement of the gallows-shaped boom 22. 
According to the drawings, the piston rod 25 is connected to a length meter 
which consists, for example, of a cord 33 attached to the back end of the 
piston rod 25 and connected via deflecting rollers 34, 35 to a rotary or 
sliding potentiometer 38 having a cord drum 36. A counter-weight 37 serves 
to tension the cord 33. In that manner the vertical displacement X of the 
piston rod 25 relative to the gallows-shaped boom 22 can be measured by 
way of the potentiometer 38. The change in shape of the dosage form D in 
question can be deduced from the vertical displacement of the piston rod 
25. 
As shown in FIGS. 3 and 4, the beaker 21 is preferably equipped with an 
intermediate base 26 which is provided with through-openings 261 for the 
test medium P. The intermediate base is, for example, a type of sieve 
plate made from glass or plexiglass. The height of the intermediate base 
26 from the beaker floor 211 is preferably adjustable. For that purpose, 
for example, it is supported on telescopically extensible feet 262. The 
dosage form D in that case lies on the intermediate base 26 and/or can be 
clamped between that base and the head portion 24. In that manner the 
requisite length of stroke, and hence the speed of the agitating device 
23, can be altered very easily. 
The mass of the piston rod 25 and of the head portion 24 are preferably 
adjustable in such a manner that the pressure that the head portion 24 
exerts if it comes to rest on the dosage form D is from approximately 5 
mN/cm.sup.2 to approximately 500 N/cm.sup.2. For example, for that purpose 
small plates 31 of different weights can simply be arranged on the piston 
rod 25 in the region of the abutment 30. That enables the activity of 
different regions of the living organism, for example in the 
gastrointestinal region, to be simulated even more accurately. 
In order to characterise the change in shape of a dosage form D, it is 
advantageous for at least the piston-shaped head portion 24 to be shaped 
in such a manner that when it comes to rest on the dosage form D it 
touches the peripheral edges thereof. The head portion 24 is, for example, 
approximately hemispherical or conical in shape. The shape of the 
intermediate base can also be made approximately to complement the shape 
of the head portion when its shape is other than a plane plate. When the 
head portion 24 comes to rest on the dosage form D, the piston rod 25 is 
displaced relative to the gallows-shaped boom 22. The length of 
displacement is detected by the length meter. The measured lengths of 
displacement of the piston rod 25 relative to the gallows-shaped boom 22 
are converted by the computer unit 6 into changes in the volume, width or 
thickness of the dosage form changing shape, expanding, disintegrating 
and/or being dissolved in the test medium. In that manner, for example, 
the increase in volume of an expanding dosage form can be determined very 
accurately. 
In the variant of the test apparatus shown in FIG. 4, the piston rod 25 is 
provided, at least at its end remote from the head portion 24, with an 
external thread 39. The bore 40 in the gallows-shaped boom 22 is likewise 
provided with a corresponding thread. As a result, the piston rod 25, 
which passes through the bore 40, is rotated (arrow R) during the 
reciprocating movement of the gallows-shaped boom 22 until the abutment 30 
arranged at the end of the piston rod 25 remote from the head portion 24 
is resting on the boom 22. Because the piston-shaped head portion 24 can 
be rotated about the piston rod 25, which acts as an axle, during its 
reciprocating movement, the agitation of the test medium P can be improved 
further. 
In order to prevent possible evaporation of the test medium P at elevated 
temperatures, for example at temperatures from approximately 32.degree. C. 
to 38.degree. C., the beaker-shaped container 21 is preferably equipped 
with a removable lid 32 which has a through-opening for the piston rod 25. 
For carrying out series tests it is advantageous for several, preferably at 
least two, agitating devices 23 to be suspended from a gallows-shaped boom 
22, the agitating devices being movable in a reciprocating manner in a 
corresponding number of beaker-shaped containers 21 containing the test 
medium P and dosage forms D arranged on the beaker floors 211 or on the 
intermediate bases 26. The capacity of the apparatus 2 can be increased 
further by providing a plurality of gallows-shaped booms 22 having 
agitating devices 23 suspended from them and a number of beaker-shaped 
containers 21 corresponding to the number of agitating devices 23. Such 
series tests are not limited merely to the changes in shape or the 
disintegration and dissolution behaviour of different dosage forms D. It 
is also possible for chemical and biological processes that play a role 
therein to be tested, for example by adding enzymes, salts, acids and the 
like to the various containers. 
The apparatus 2 according to the invention for simulating the physiological 
conditions is used preferably in an analysis system for determining the 
change in shape, the disintegration behaviour and/or the dissolution 
behaviour and the active-ingredient release of pharmaceutical dosage 
forms. In that system, an analysis unit 4, for example a spectroscopic 
analysis unit, is connected to the simulation apparatus 2 for preferably 
continuous determination of the active-ingredient concentration in a test 
medium. In that manner it is possible for the change in volume or width 
and/or thickness of a dosage form to be determined continuously, and for 
the release of active-ingredient, the energy absorption and the progress 
of chemical or biological processes to be detected in parallel therewith. 
The analysis system according to the invention can be used to test and to 
characterise tablets, dragees, capsules, transdermal systems, intrauterine 
inlays, suppositories, ophthalmological inlays or implants, or devices for 
use in veterinary medicine.