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Intraoral Drug Delivery Microsystem

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 SPECIAL ISSUE PAPER 1609

Intelligent intraoral drug delivery microsystem

T Velten1
, H Schuck1, T Knoll1, O Scholz1, A Schumacher 2, T Gottsche2, A Wolff 3, B Z Beiski3, and IntelliDrug Consortium4
1
Fraunhofer-Institute for Biomedical Engineering, St Ingbert, Germany
2
HSG-IMIT, Villingen-Schwenningen, Germany
3
Assuta Medical Centers, Tel-Aviv 62748 and Saliwell Ltd, Harutzim, Israel
4
MT Promedt Consulting and Charite Universitatsmedizin (Germany), Valtronic SA (Switzerland), Warsaw University
of Technology and ASM Centrum Badan i Analiz Rynku (Poland), Universita di Palermo and Universita Federico II di
Napoli (Italy), Hospital Clnico San Carlos (Spain), and Relsoft Systems, Bio Dar Ltd, and Anti Drug Authority (Israel)

The manuscript was received on 16 November 2005 and was accepted after revision for publication on 10 April 2006.

DOI: 10.1243/09544062JMES237

Abstract: The authors report on the concept and development of an intelligent intraoral drug
delivery microsystem, that provides an alternative approach for the treatment of addiction
and chronic diseases. The drug delivery system (DDS) comprises a medication replacement
reservoir, a medication release mechanism, a built-in intelligence, a remote control, micro-
sensors, and microactuators. It is thus able to release the medication in a controlled manner
according to the patient needs.
The emphasis of this article is on the application of sensors and microfluidic components in a
real microsystem and also showing some details of two system components, namely, the osmo-
tic pump and the flow sensor. The motivation for the microfluidic approach, the concept of the
DDS, the requirements for this specific application, and the arising problems will be presented
and discussed. Regarding the sensors and actuators, the problems mainly concern size and
power consumption. A major challenging aspect of microfluidic component development is
to avoid clogging of small channels because of particles and recrystallization of saturated fluids.

Keywords: microfluidics, microflow sensor, osmotic pump, drug delivery, intraoral

1 INTRODUCTION reach the circulation. Other major disadvantages of

There are several methods for medication delivery
such as intravenous, rectal, and oral delivery. The
oral route is by far the most convenient one. How-
ever, taking medicine as pills has many disadvan-
tages such as poor compliance, i.e. the patient does
not take the pills as prescribed. Another disadvantage
is the poor bioavailability of drugs, which use the
gastro-intestinal (GI) route for absorption into the
organism. This is due to the harsh chemical environ-
ment of the GI tract (pH in stomach is 0.9 4.5 and
pH in intestine is 8.1 9.3), the adverse chemical enti-
ties such as salts and enzymes, and the hepatic first
pass metabolism. The consequence is that only a
fraction of the orally taken medicine will finally


Corresponding author: Fraunhofer-Institute for Biomedical
Engineering, St Ingbert, D-66386, Germany. email:
thomas.velten@ibmt.fhg.de
taking pills are that it leads to a fluctuating drug
level, that the dose administration is not controlled
in real time, and that the dose is usually not
personalized.
Modern drug delivery systems (DDSs) are attempts
to overcome some of these deficiencies. DDSs for
contraception are well known and may be implanted
[1] or transdermal [2]. Additionally, there are
implanted insulin pumps [3], which represent
highly sophisticated DDS. However, to the best of
our knowledge, there are no available DDS driven
by electronics and software. Most of them are con-
trolled by pharmaco chemical means.
The authors report on an intelligent intraoral drug
delivery microsystem, that provides an alternative
approach for the treatment of addiction and chronic
diseases (patents pending). This system is in con-
trast to invasively implanted DDS positioned in
the most accessible human body opening, the
mouth, and thus is inserted in a non-invasive way.

JMES237 # IMechE 2006 Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
1610
2 REQUIREMENTS AND CONCEPT OF THE DDS
2.1 Requirements of the DDS
The intraoral DDS should have the maximum size of
two molar teeth. Thus, miniaturization is a major
challenge that the development of the DDS is
facing. The DDS does not only comprise the earlier
described components, but also includes a battery
as power source. There exist commercially available
tiny batteries (such as SR421SW from Maxell having
a volume of 40 mm3 and a nominal capacity of
12 mAh at 1.55 V), which meet the size constraints
of the DDS. As the capacity of such tiny batteries is
very restricted, the power consumption of the DDS
subunits has to be kept as low as possible, which is
another big challenge.
One application of the described DDS is the treat-
ment of addiction and chronic diseases. An example
of medicine that can be delivered by the DDS is nal-
trexone, an opioid antagonist approved for the treat-
ment of heroin addicts. The DDS should be able to at
least contain the amount of naltrexone that is
necessary for a two-week treatment. Replacing bat-
teries should not be necessary within the two-week
treatment. An effective treatment necessitates a con-
stant blood plasma level of naltrexone. Thus, a
defined dose of naltrexone must be administered
quasi continuously (i.e. 24 times per day) during
the whole duration of the treatment.
2.2 Concept of the DDS
The intraoral DDS is a dental appliance-supported
device having the size of about two molar teeth,
before further miniaturization will be performed. It
can be easily inserted and removed from the
mouth. It shall be able to deliver a defined amount
of medication at defined time intervals or at defined
points in time for a period of few weeks. The current
medication level in the drug reservoir of the DDS as
well as the release rate will be constantly monitored.
All medication delivery parameters can be adjusted
by means of a personal remote control, which wire-
lessly communicates with the oral device. A system
overview is shown in Fig. 1. The overall system is
divided into the intraoral drug delivery device and
the external remote control unit. The remote control
unit is not further described in this article. The
intraoral system includes a drug reservoir, a drug
level sensor for monitoring the remaining amount
of drug, a pump as driving mechanism, a controllable
valve, a flow sensor for sensing the amount of drug
administered, and an iontophoresis subsystem. All
the mentioned subcomponents together with the
electronics and power supply unit will be integrated
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
T Velten et al.
Fig. 1 Schematic overview of the intraoral DDS
into a housing, having the maximum size of two
molar teeth (Fig. 2).
Released drugs will be delivered through the sub-
lingual and/or buccal tissue, but may alternatively
be directed to the GI route. Both sublingual and
buccal tissues are well known to show a high per-
meability for drugs [4] yielding high bioavailability
as they avoid the obstacles found in GI drug admin-
istration. The iontophoresis subunit will enhance
bioavailability as it drives electrically charged drug
ions away from an electrode and into the tissue
by means of a low-level direct current (DC).
Iontophoresis is an effective and rapid method of
delivering water-soluble, ionized medication [5].
Where the drug molecule itself is not water-soluble,
it may be coated with a layer of water-soluble
radicals.
The DDS is designed to be well suited for water-
soluble drugs. In principle, the medication can be
placed into the drug reservoir in solid or liquid
state. From the technical point of view a liquid
drug (drug solution) is preferred because, in prin-
ciple, many technical solutions such as, microchan-
nels, micropumps, and micromass flow sensors for
handling and metering of tiny amounts of liquid
are well known and already available. In contrast,
the capacity of the drug reservoir is not only limited
by its geometrical dimensions but also by the maxi-
mum achievable concentration of the dissolved
medication. Thus, it is clear that a solid drug formu-
lation will lead to a much higher drug load and thus
to much higher time intervals between refills than a
liquid one. To be able to take advantage of both,
the high drug load and the available microfluidics
technology, it is desired to initially put a solid drug
into the reservoir and to dissolve the drug to end
JMES237 # IMechE 2006
 Intelligent intraoral drug delivery microsystem
Fig. 2 Intraoral DDS and its position in the lower jaw
up with a drug solution. This makes only sense if the
water for dissolving the drug comes from a source
external to the DDS housing. Otherwise, the joint
volume of solid drug and water would be identical
to the volume of an initial liquid drug formulation.
As the DDS will be located in the oral cavity,
enough water is available from saliva. To avoid salts
and biological substances such as bacteria to enter
the DDS, a filter membrane with appropriate pore
size has to be used. If the used membrane is
semi-permeable and is in direct contact with the
drug reservoir, water will be forced to enter the
drug reservoir and to dissolve the drug. This mechan-
ism leads to a saturated state where the drug
reservoir contains the partially dissolved drug
surrounded by a saturated drug solution. In addition,
an osmotic pressure will build up inside the drug
reservoir. This pressure can be used as a kind of
pump (osmotic pump), which is the driving mechan-
ism for the dissolved drug to be pushed out of the
reservoir across a control valve. The big advantage
of this kind of pump is that it requires no additional
space and that it does not drain the power source of
the DDS. In case the osmotic pressure build up by
the drug is not sufficient, release enhancers (e.g.
salts) that lead to higher osmotic pressures may be
added.
To enable the control of drug administration in
real time, a valve is needed, which is controlled by
the systems electronics and software algorithm.
The valve is built by a fluidic device having a flow
resistance that can be varied by applying a suitable
voltage. In principle, monostable or bistable valves
[6, 7] can be applied. The critical parameters are
JMES237 # IMechE 2006
1611
power consumption and performance. The valve in
its closed stage has to withstand the osmotic
pressure that is arising inside the drug reservoir.
The design of the valve has to take into account
that the maximum flowrate (leakage) in the closed
state, as well as the maximum flowrate in the open
state, meets the system requirements. Both values
strongly depend on the pharmaceutical parameters
of the medicine to be administered. Typical values
for the maximum flowrate are in the order of several
tens of ml/h. Medication is delivered by opening the
valve for a certain time, thus producing medication
pulses. The dosage of the medication delivery is
accomplished by modulation of the actuation fre-
quency or the width of the opening pulses. The
choice of these timing parameters depends on medi-
cal aspects characteristic for the specific drug and
also on technical aspects such as power consump-
tion per valve actuation and flow sensor resolution
(discussed subsequently).
To obtain reliable information about the amount
of drug inside the reservoir, the DDS will be equipped
with a drug level sensor. As the drug will be stored in
solid form, the sensor must detect the time-
dependent amount of the non-dissolved drug
remaining in the reservoir. The major requirements
for the drug level sensor are extremely small size
and low power consumption. The concept of the
conceived drug level sensors and the results of first
experiments will be described elsewhere.
Additionally, the DDS is equipped with a flow
sensor, which will carry out flowrate measurements
in order to control the drug delivery rate. This
sensor is described in section 4.
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
1612
3 OSMOTIC PUMP
As actuation mechanism for the drug solution, an
osmotic pump has been developed. Provided that
the osmotic pressure inside the drug reservoir
exceeds the osmotic pressure of saliva, water from
the saliva permeates through the semi-permeable
membrane, dilutes part of the solid drug, and the
resulting solution is pushed out of the drug reservoir
(Fig. 3).
To investigate the flowrate and the pressure that
can be achieved by the osmotic pump, an exper-
iment was set up as shown in Fig. 4. The osmotic
chamber contains the solid osmotic agent, which is
placed inside a container filled with artificial saliva.
Owing to osmosis, water from the saliva permeates
through the semi-permeable membrane into the
osmotic chamber. This leads to a flowrate J, which
depends on the composition of the osmotic agent
and the solvent, as well as on the water permeability
K, the area A of the membrane, and the external
pressure pe. If the valve is open, the flowrate J of
the osmotic pump can be directly measured. With
closed valve, the pressure p increases until, after a
certain time, it reaches a final value, which is equal
to the osmotic pressure po.
For the experiments, the conditions listed in
Table 1 have been used.
Under these conditions, the normalized flowrate
J/A has been measured to be 0.3 ml/h m2. The osmo-
tic pressure po has been measured to be 38 kPa. As
the membrane area A of the final device will be
20 mm2, a flowrate of J 6 ml/h can be expected.
Fig. 3 Osmotic pump as actuation mechanism
Fig. 4 Schematic of the experimental setup
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
T Velten et al.
Table 1 Conditions for the osmotic pump experiment
Item Description/value
Osmotic agent Saturated solution of naltrexone HCl
Solvent Artificial saliva
Temperature T 310 K
Semi-permeable Cross-linked polyamide composite
membrane membrane
Membrane area A 70 mm2
4 FLOW SENSOR
For the miniaturized DDS, a micromachined mass
flow sensor seems to be well suited because of its
small dimensions. Ashauer et al. [8], for example,
report on such a sensor, that is based on a thermo-
transfer measuring principle.
The fluid is led through a microchannel across the
sensor area and is heated by a heater structure on the
sensor. The velocity-dependent change of the temp-
erature distribution inside the fluid is detected by
temperature sensors. Thus, the flowrate of the fluid
can be determined.
The authors report on a similar flow sensor, which
is also based on the thermotransfer principle. In con-
trast to the sensor reported by Ashauer et al., our
sensor contains no fragile membrane. This adds to
the robustness and reliability of the sensor. The
developed micromachined flow sensor consists of
two parts, which are microfabricated on 400 glass
wafers (Pyrex 4470) (Fig. 5). The bottom part carries
resistor structures made from platinum and con-
ducting paths made from gold. Both metal layers
are structured using lift-off processes, followed by
the deposition of an 800 nm thin passivation layer
of silicon nitride and silicon dioxide. The resistor
structures extend to 95 mm (heater) and 67.5 mm
(per PTC resistor) along the channel. The channel
walls are realized by the lithographic structuring of
a negative photoresist (X-AR 4400-25, AllResist)
with a thickness of 15 mm. The width of the flow
channel is 50 mm. The top part of the chip contains
the holes for the fluid inlet and outlet, which are
made by micropowderblasting. Both parts of
the chip are bonded to each other using a
Fig. 5 Flow sensor (thermotransfer principle)
JMES237 # IMechE 2006
 Intelligent intraoral drug delivery microsystem
Fig. 6 Picture of the flow sensor (on a E1 coin)
low-temperature adhesive bonding process. The
fabricated flow sensor is depicted in Fig. 6.
The sensor resolution has to be adapted to the low
mass flow of the drug solution. To increase the flow
velocity and thus the sensor resolution, the height
of the microchannel across the sensor area may be
designed very small. In contrast, a small distance
between the heater structure and the ceiling of
the microchannel may impair the sensor perform-
ance because of increased heat dissipation.
Additionally, a small distance will increase the risk
of clogging because of particles or air bubbles. Opti-
mum dimensions for the microchannel can be
obtained by performing computer simulations.
Figure 7 shows the simulated heat distribution in
the immediate vicinity of the heater surface in the
Fig. 7 Temperature distribution (a) and difference (b) at the floor by flow variation
JMES237 # IMechE 2006
1613
channel (15 mm height and 50 mm width) for flow
values of 0 and 50 ml/h. For this simulation, the
effect of the passivation layer has not been taken
into account. The simulation was performed for a
heater power fixed to 1.7 mW. This rather low but
realistic value has been chosen with regard to the
limited capacity of the battery, which will be used
for powering the DDS. The flow of 50 ml/h
(Fig. 7(a)) deforms the temperature distribution
(solid curve). To determine the best position of the
up- and downstream sensors, the temperature differ-
ence between the dotted and the solid curves was
calculated. The result is shown in Fig. 7(b).
The highest absolute amount of temperature
difference indicates the best position for the temp-
erature sensors in order to achieve the optimal
sensor sensitivity. A flow of 50 ml/h generates a 1 K
difference of temperature between the heater
centre and a point 30 mm upstream or downstream.
Because in the actual design the extensions of
heater and temperature sensors along the channel
are 67.5 and 95 mm, respectively, it is not possible
to realize the optimal distance of 30 mm between
the centre of the heater and the centre of the temp-
erature sensor without an overlap of these two com-
ponents. Therefore, the temperature sensors have
been placed as close to the heater as practicably
possible.
Figure 8 shows the temperature distribution at
different heights in the channel. Again, the influence
of the passivation layer on the temperature distri-
bution has been neglected for the simulation. The
thickness of this layer is only 800 nm, and the
simulation of such a small layer requires a fine-
meshed simulation grid and consequently excessive
computational efforts. As can be seen in Fig. 8, the
temperature above the heater decreases by 1 K
3 mm. If it is considered that the passivation layer
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
1614 T Velten et al.

extension of the resistor along this fluidic channel.

Having a very long temperature resistor would
mean that only a minor part of the resistor would
experience a significant temperature change by
the heat transferred from the heater to the tempera-
ture resistor (Fig. 7(b)). This would have a negative
effect on the sensor sensitivity. The earlier men-
tioned dimensions (width 50 mm and height
15 mm) are regarded as a reasonable compromise
among sensitivity, power consumption, and
response time. The response time has been simu-
lated (software FEMLAB) for the earlier mentioned
dimensions for the fluid channel and the resistors.
The simulation results predict a response time of
200 ms (Fig. 9(a)). This is in good agreement
Fig. 8 Temperature distribution along the channel at with the measured response time (Fig. 9(b)).
different heights, simulated for a flow of 50 ml/h On the basis of on the simulation results, the flow
sensor was designed as depicted in Fig. 10. The
temperature sensors were placed as close as poss-
of silicon nitride and silicon oxide has a thermal ible to the heater to get a good sensitivity and a
resistance of 0 K/W and compared this with the short response time. To achieve a high power effi-
thermal resistance of water (33 K/W), it can be ciency, the resistance of the heater should be
roughly estimated that the temperature maximum much higher than the internal resistance of the
in the passivation layer will decrease 1 K/mm. battery (the resistance of two Maxell SR421SW
Thus, the effect of the 800 nm thick passivation batteries in series amounts to 200 V, as has been
layer on the temperature maximum is .0.1 K and experimentally determined). However, the maxi-
can be neglected. mum power can be drawn, when source and load
The mass flow sensor, especially the heater of the resistances equal. Therefore, it is necessary to
mass flow sensor, is the most power consuming
component of the whole DDS. A continuous oper-
ation of the flow sensor would drain the battery
within minutes. To achieve the envisaged operation
time of about two weeks, it is indispensable to keep
the overall measurement time as short as possible.
This means that the heater of the flow sensor will
only be switched on if a measurement is done.
Additionally, the time per measurement should be
kept as short as possible. This can be achieved by
designing the sensor for a short response time.
This is the time it takes to reach a thermal steady
state, and thus well defined and reproducible con-
ditions, after switching on the heater of the flow
sensor. The response time strongly depends on
the fluid velocity for a certain flow. According to
the equation of continuity, the fluid velocity for a
certain flow depends on the cross-section of the
fluid channel. However, a small cross-section does
not only have the positive effect of decreasing the
response time, but also has some drawbacks:
the risk of clogging is increased. Additionally, the
space for positioning the resistors for the heater
and for the temperature sensors is limited. To mini-
mize the power consumption, these resistors should
have a rather high value. As a consequence, the
conducting path of the resistors should be rather
long. To realize a long meandric resistor inside a Fig. 9 Simulated (a) and measured (b) sensor
narrow fluidic channel necessitates a large responses after switching on the heater

Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science JMES237 # IMechE 2006
 Intelligent intraoral drug delivery microsystem 1615

Fig. 10 Layout of heater and temperature sensors

adapt the resistance of the heater to the internal

resistance of the battery accordingly. Values in the
range of 100 V are obtained by using a Pt-layer
of 80 nm thickness. This layer was structured in
a lift-off process to realize the heater and the
temperature sensors.
To avoid significant heating by the temperature
sensors, their resistance values are designed three
times higher than the that of the heater. All circuit
paths leading from the bond pads to the resistors Fig. 11 Measured signals of IBMT (a) and commercial
consist of 80 nm platinum and an additional layer Sensirion (b) flow sensor. The measurements
of 300 nm gold to prevent unnecessary energy con- were performed at 313 K
sumption and heating of the whole system.
The complete flow sensor consists of two chips:
the lower chip carries the heater and resistor struc- Figure 11 shows the sensor signals for a flow that
tures described earlier and the upper closes the alternates between values of 0 and 10, 20, 30, 40,
fluid channel. Both chips are bonded to each other and 50 ml/h. The measurements were performed
using a low-temperature adhesive bonding process at a temperature of 313 K. There is a very good cor-
at 373 K. At this temperature, the top part was manu- relation between the signals of the sensor under test
ally aligned to the bottom part by means of an optical and the Sensirion reference sensor. The sensor res-
microscope. The fluidic connection of the sensor is olution is clearly below 5 ml/h. A linear temperature
established by tubings (PEEK), which are glued to dependence of the sensor offset has been observed.
the powder-blasted holes of the top chip. The The sensor sensitivity is not affected by temperature
assembled flow sensor is mounted on an interface changes. Details of these measurements dealing
ceramic substrate containing screen-printed con- with sensor accuracy, reliability, and the influence
ducting pads. After sensor fabrication, the sensors of ambient conditions on the sensor signals will
electronic and fluidic functionality was tested. To be reported elsewhere.
judge the performance of the sensor, a commercial
sensor (SLG1430-150 from Sensirion, Switzerland)
was fluidically connected in series and both outputs
5 POTENTIAL PROBLEMS OF THE DDS
were compared. A precision syringe pump (Type
MDSP3f, MMT, Germany) generated different flows
The fluidic network of the DDS is rather complex and
(10, 20, 30, 40, and 50 ml/h), which were pumped
all components of this network will influence one
through the sensor under test and the Sensirion
another. Thus, a coordinated design of the fluidic
sensor. To avoid any temperature influence from
components is indispensable. The following list
the environment, the measurement arrangement
shows some examples of such dependencies.
was placed in a climatic chamber at fixed tempera-
ture conditions. Additionally, the temperature 1. The prerequisite to be able to determine the drug
inside the chamber was measured time-correlated dose administered to the oral cavity is that the
to record remaining temperature fluctuations concentration of the drug solution is constant
which were in the range of +1 K. and well known. This can be achieved by a

JMES237 # IMechE 2006 Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
1616
saturated solution. To ensure that the solution
inside the drug reservoir is always saturated, it
is necessary that the velocity of the drug-dissol-
ving process is matched with the velocity of
water from saliva inflow through the semi-per-
meable membrane.
2. As the drug solution is incompressible, the drug
outflow in the case of an open valve is equal to
the water inflow through the semi-permeable
membrane.
3. A closed valve will lead to a high pressure (osmotic
pressure) in the part of the fluidic system between
the semi-permeable membrane and the valve.
Depending on the osmotic agent/drug, this
pressure can be of the order of several bars. As
micromachined silicon mass flow sensors usually
contain thin membranes, such flow sensors may
not bear such high pressures. To avoid destruction
of the flow sensor, it must not be located in the
fluidic pathway between semi-permeable mem-
brane and valve. To avoid destruction of the flow
sensor, in the valve open state, a fluidic resistor
should be added to the pathway between valve
and flow sensor. In this case, the pressure will
drop at this resistor and not at the microchannel
across the flow sensor membrane. In the case of
using the earlier described dedicated flow
sensor, this problem is less severe because this
sensor, in contrast to most of the micromachined
flow sensors described in the literature, does not
contain a fragile membrane.
4. The fluidic resistance of this additional fluidic
resistor will influence the outflow of drug
solution.
5. The higher the drug outflow, the likelier will the
flow sensor be able to resolve the flow.
6. The higher the flow velocity at the flow sensor,
the shorter is the necessary on time of the
heater of the thermotransfer flow sensor. This
has a strong influence on the overall power con-
sumption because the heater of the flow sensor
is one of the main current consumers of the
DDS.
7. A large flow will allow a short open time of the
valve. In the case of a normally closed mono-
stable valve, this has a big influence on the
power consumption of the valve.
Severe problems may arise due to particles or air
bubbles, which first of all may enter the DDS
during the refilling of the drug reservoir. They may
lead to clogging of channels. Particles or air bubbles
at the flow sensor can lead to erroneous measure-
ment results. To avoid particles entering the fluidic
system, a membrane with a few micrometres pores
size will be used at the outlet of the drug reservoir.
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science
T Velten et al.
6 RELIABILITY AND SAFETY ASPECTS
The DDS is an active medical device which delivers a
medicine. Depending on the kind of medicine, a mal-
function (overdose or underdose) of the DDS may
have severe impact on the patients health. Thus,
the system design should consider all kinds of
malfunctions.
First of all, the system housing must ensure that a
destruction of the housing resulting in a sudden
release of the whole amount of drug will not occur
during typical actions such as eating, drinking, and
speaking. Selecting appropriate materials (e.g.
metals) and using an appropriate design will enable
to fulfil this requirement. Another topic concerning
the choice of material is biocompatibility. All
materials that are in direct contact with the human
body must be approved as medical grade.
It has to be assured that a breakdown of the DDS
control unit will not lead to an overdose. A good
measure to achieve this goal is to use a monostable
valve, which is normally closed. The disadvantage
of a monostable valve, in contrast to a bistable
valve, is that it consumes power during the whole
open time. Malfunction of the DDS control unit
can nevertheless lead to an overdose, if the nor-
mally closed monostable valve is kept open for a
very long time. In this case, limiting the maximum
achievable drug flow would help. The maximum
drug flow is mainly determined by the efficiency
of the osmotic pump and the fluidic resistance of
the system. The efficiency of the osmotic pump is
determined by the used osmotic agent and the
area of the semi-permeable membrane. These par-
ameters have to be adjusted to ensure a maximum
drug delivery which is below the noxious dose for
constant administration of the used drug.
As mentioned earlier, the drug flow sensor is rather
power consuming. Thus, it is not possible to make con-
tinuous flow measurements. The flow sensor is only
active for some control measurements during the
valve open phase. To increase safety of the system,
additional control measurements may be made
during the valve closed phase. Additionally, safety
can be improved by exploiting the effects of redundant
sensor information. In principle, the drug flow can be
determined by the decrease of the drug level, and the
drug level can be determined by integrating the
measured drug flows. These indirect measurements
are not expected to be very accurate, but they can be
used for a rough verification of the sensor signals.
7 CONCLUSIONS
In contrast to taking pills, the use of a DDS has the
potential to overcome many hurdles such as poor
JMES237 # IMechE 2006
 Intelligent intraoral drug delivery microsystem
compliance, poor bioavailability, and poor drug
release control. In this article, a highly technical
intraoral DDS has been described, which is intended
to be used for the treatment of addiction and chronic
diseases. Besides the system overview, the require-
ments and dependencies of the complex micro-
fluidic system have been pointed out. Additionally,
safety aspects have been discussed taking into
account that a malfunction of the DDS may have
severe impact on the patients health. With all the
obstacles and limitations in mind, the present DDS
may enable to control plasma levels of medications
in a much more accurate manner than current oral
or dermal drug administration methods.
ACKNOWLEDGEMENTS
The authors would like to acknowledge the strong
support by Werner Haberer and Timo Koch, who
performed the sensor measurements. This work
was supported by a European Grant under the Sixth
Framework Project IntelliDrug IST-FP6 Contract
no. 002243.
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APPENDIX
Notation
A membrane area (m2)
J flowrate (m3/s)
K water permeability (m3/(m2s Pa)
pe external pressure (Pa)
po osmotic pressure (Pa)
T absolute temperature (K)
Proc. IMechE Vol. 220 Part C: J. Mechanical Engineering Science