Laser Drilling Enables Advanced Drug Delivery Systems - Coherent

Laser Drilling Enables Advanced Drug Delivery Systems
by Frank Gaebler, Coherent, and Graham Coffee, Control Micro Systems
Laser drilling has become well established as an economically viable method for producing
sub-millimeter sized holes in tablets. This article reviews the basics of the laser tablet drilling
process, and provides some insight into how laser beam parameters affect process economics and
hole quality.
Background
The benefits of sophisticated drug delivery systems are well proven, and include decreased
dosing frequency, more consistent drug concentration in the blood, and even customized delivery
profiles. Osmotic drug delivery systems, in particular, have proven especially valuable for
providing controlled release of molecules with inherently low oral bioavailability due to
solubility or permeability limitations. The typical osmotic delivery system for a poorly soluble
molecule comprises a drug layer and a “push” layer, surrounded by a semi-permeable membrane.
After ingestion, water enters through the semi-permeable membrane causing the push layer to
expand; this forces drug to be pumped out at a controlled rate through a small orifice in the drug
layer side of the membrane.
The typical orifice size in osmotic pumps ranges from about 600 µm to 1 mm. The tolerances on
hole diameter and shape are usually relatively loose, at least by the standards of other precision
manufacturing tasks. A nominal 600 µm hole usually has a ±100 µm tolerance on diameter, and
an allowable ellipticity of 1.0 to 1.5. Holes of these dimensions and tolerances could certainly be
produced by purely mechanical means; however, no mechanical method has proven capable of
working at throughput rates that are consistent with other stages of the pharmaceutical
manufacturing process. In contrast, laser tablet drilling supports throughput rates of up to
100,000 tablets/hour, and can easily produce holes with the necessary dimensional tolerances and
cosmetic appearance. As a result, laser drilling has become the technology of choice for this
type of orifice production. Laser drilling is also the preferred technology for use with other drug
delivery systems whose operation is critically dependent upon the presence of one or more small
holes in the tablet coating.
Laser Drilling System Operation
The figure shows the main functional elements of a commercial, laser based tablet drilling
system. This particular configuration utilizes two laser drilling stations and can drill either one
or both sides of a tablet.
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Bowl
Feeder
Conveyor
Presence
Sensor
Color
Sensor
Laser
Drilling
System
Vision
System
Rejects
Blow
Off
System
Presence
Sensor
Color
Sensor
Inverter
Laser
Drilling
System
Vision
System
Rejects
Blow
Off
System
Collection
Drum
To begin the process, tablets are first introduced on to a single line conveyor from a bowl feeder.
A color sensor views each tablet to determine which side is facing up. In the specific case of
osmotic pumps, tablets typically are colored brown on the push layer side with a pink or yellow
drug layer side. The hole thus needs to be drilled only in the yellow (or pink) side.
Next, a presence sensor detects the passage of a tablet and then triggers the laser drilling process
if the results from the color sensor were that the tablet was facing right side up. Tablets then
pass through a machine vision inspection system. A digital image of each passing tablet is
acquired and compared against the four possible outcomes, listed in the table. Two of these
outcomes constitute a “pass” and two are considered a “reject.”
Pass Reject
Dilled and top side up Dilled and bottom side up
Not drilled and bottom side up Not drilled and top side up
Rejected tablets are removed from the conveyor by an air activated blow off system. Because of
the speed at which the conveyor moves and the physical response time of the blow off system,
the reject mode is activated as soon as a failed tablet is sensed by the vision system. This
typically causes one or two tablets ahead of the rejected unit to be expelled as well. Then, the
reject state is usually left on until the system sees five tablets in a row that meet either of the two
pass criteria. An additional presence sensor downstream from the blow off verifies that no
tablets are passing through the system when the reject condition is set to “on.” Despite the fact
that some good tablets are rejected by this necessarily rigorous approach, the system still
typically operates at 98% efficiency (tablets in/tablets out).
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After transiting the first laser drilling station, tablets pass single file through an inverter, and then
continue on the conveyor through a second laser drilling station. This second laser drilling
station operates in exactly the same way as the first. Its function is to drill any tablets that were
wrong side up when they passed through the first drilling station. Alternately, to drill both sides
of a tablet, the color sensors in both stations are set to trigger the drilling process regardless of
tablet orientation. Also, in that case, the vision inspection system is programmed to reject tablets
only when no hole is detected. At the end of the line, processed tablets are fed into a collection
drum, ready for final coating and printing.
Laser Requirements
Virtually any type of industrial laser can easily produce holes with the sizes and tolerances
required for tablet drilling. Therefore, the primary selection criterion for the laser source is the
throughput speed it can support. Secondary to this are considerations such as operating costs and
uptime.
The maximum achievable throughput speed for tablet drilling is influenced by several laser
characteristics. For example, if all other factors are equal, throughput increases when using a
laser whose output wavelength is well absorbed by the material to be processed. Also, high
absorption in the processed material ensures that no significant laser power penetrates through to
other layers in the delivery system, where it might cause damage.
The organic materials used in drug delivery systems nearly all display strong absorption in the
infrared, so the carbon dioxide (CO2) laser, with nominal output at a wavelength of 10.6 µm, is
well matched for this task. In contrast, many organics are transparent at the near infrared output
wavelength (1.06 µm) of industrial lasers based on Nd:YAG. From a practical standpoint,
industrial CO2 lasers represent a very mature technology offering excellent reliability
characteristics and low consumables costs. In fact, they offer lower overall cost per watt than
any other type of industrial laser.
Most organics are also strongly absorptive in the deep ultraviolet, and could therefore be
processed using excimer lasers. However, the material removal mechanism in the ultraviolet is
substantially different than in the visible and infrared. Specifically, visible and infrared lasers
remove material in a thermal process. In contrast, deep ultraviolet lasers directly break
interatomic bonds, atomizing the material in a process called photoablation. Generally, heating
removes material much faster than photoablation, making the former method better suited for
high speed tablet drilling. Photoablation is more advantageous in high precision applications, in
which either the amount of material to be removed is small or processing speed is a secondary
concern.
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Currently, there is quite a diverse range of commercially available CO2 lasers, offering output
powers from a few watts to multi-kilowatts. Furthermore, some CO2 lasers operate in continuous
wave (CW) mode, while others are pulsed. A CW laser produces an uninterrupted beam of light,
while a pulsed laser emits a stream of very short duration (

processing using galvanometer beam steering also allows the process to produce multiple holes
per tablet as well as other geometries, such as characters or graphics, although rates may be
affected.
Incoming
Laser
Light
Focused
Deflected
Beams
Scan
Mirror
Scan
Lens
Tablet Hit with
Several Laser
Pulses as It Moves
While the multiple pulse method increases the complexity of the laser beam delivery system, it
enables a given processing task to be performed using about three to four times less laser power
than in the single pulse case. This allows the use of a lower power, and therefore less costly,
laser, and easily offsets the expense associated with greater system complexity. The maximum
number of pulses that can be used to process a single tablet depends upon conveyor speed, the
field of view of the scan lens, and laser repetition rate. A typical tablet drilling process utilizes
around nine laser pulses in order to drill a single hole.
The exact pulsing characteristics of the laser have a significant impact on the economics and
efficiency of the drilling process. For example, the graph compares the output power as a
function of time for a typical flowing gas CO2 laser with that of a slab discharge CO2 laser. The
output pulse from the flowing gas laser is roughly triangular in shape. In contrast, the short rise
and fall times of the slab discharge laser lead to an essentially square wave shaped pulse. While,
in the case illustrated, the peak power of the flowing gas laser is higher than that of the slab
discharge laser, much less of this power is actually usable for cutting (the specific cutting
threshold power is highly dependent upon the particular material being processed).
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Laser Power
Usable
Cutting
Energy
Cutting
Threshold
Power
0 100 200 300 400
Time (microseconds)
Flowing Gas Laser
Laser Power
Usable
Cutting
Energy
Cutting
Threshold
Power
0 100 200 300 400
Time (microseconds)
Slab Discharge Laser
The fact that each square wave pulse delivers more useful cutting energy means that it takes
fewer of these pulses to perform a given processing task. Because of the interrelationship
between maximum possible pulse count and throughput speed in on the fly drilling, this
translates into a wider process window and greater flexibility. In addition, the reduction of waste
energy serves to further minimize any heat induced damage in the processed material.
Control Micro Systems utilizes Diamond K Series slab discharge CO2 lasers from Coherent for
many of its tablet drilling systems. In addition to the advantages of square wave pulsing, the
Diamond K Series also delivers several other benefits for on the fly processing. The ability of
these lasers to provide “power on demand” is probably the most important of these. This refers
to the capacity to control the laser’s pulsing characteristics, in real time, down to the single pulse
level if necessary. In contrast, many industrial lasers operate with a fixed or narrowly variable
pulse repetition rate. Moreover, in most other laser types, individual pulses cannot be relied
upon to produce consistent results because the laser takes several pulses to reach its steady state
performance level. However, the slab discharge design does not have this limitation and can be
perfectly pulsed instantaneously. Thus, power on demand is important because it allows the
laser to be slaved to any arbitrary (and even variable) feedrate in a real production line. This is
substantially simpler than attempting to adjust the mechanics of the conveyor system so that
tablets are supplied at exactly the right time to synchronize with a fixed pulse rate laser.
Conclusion
The development of more sophisticated drug delivery systems permits the use of a wider range
of chemical entities, but the complex structure of these devices often creates greater technical
difficulties in production. The laser has shown itself to be a reliable and cost effective tool that
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delivers processing capabilities not readily attainable through any other means. It has already
proven to be an enabling technology for tablet drilling in the production of osmotic pumps, and
will undoubtedly be useful in overcoming other challenges faced by pharmaceutical
manufacturers in the future.
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