The benefits of sophisticated drug delivery systems include decreased dosing frequency, more consistent drug concentration in the blood and even customized delivery profiles. In particular, osmotic drug delivery systems have proven 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 the 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 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 as well as other drug delivery systems whose operation is critically dependent on the presence of one or more small holes in the tablet coating.
The main functional elements of a commercial, laser-based tablet drilling system are shown in Figure 1 (below). This particular configuration utilizes two laser drilling stations and can drill either one or both sides of a tablet.
|Figure 1. The main elements of a commercial, laser-based tablet drilling system.|
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. For 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. The laser drilling process commences 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.
|Drilled and top side up||Drilled 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. 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 rigorous approach, the system still typically operates at 98% efficiency (tablets in/tablets out).
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. 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.
Virtually any type of industrial laser can 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 considerations are factors 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. High absorption in the processed material also ensures that no significant laser power penetrates through to other layers in the delivery system, where it might cause damage.