A new near-infrared inspection system for tablets has just completed beta-testing at Sanofi-Synthelabo Research, Malvern, PA. A division of Sanofi-Synthelabo, Sanofi-Synthelabo Research packages drug supplies for clinical trials. Among the products produced at Sanofi-Synthelabo Research are blister-packs of tablets. As part of a clinical trial, subjects are given prescribed doses of a drug, which sometimes can include placebos. The trial is sometimes "Blinded," which means neither the administrator nor the subject knows which dose the subject is receiving, so both tablets must look identical. "The two items must look the same, so it is a challenge to keep track of which is which during packaging," says Richard Winokur, director, clinical investigational products.
Typically, to minimize the chance of any mix-up, the company runs different doses separately, and cards them, so, if needed, the product can be combined to get the dose combination desired. As a final check, the company tests finished packages to ensure that the tablets are in their proper places. "The problem with this is that it is a destructive test, and you have to wait for the results of the chemical analysis," says Winokur.
|A separate fiberoptic cable transmits light to the analyzer from each blister being inspected.|
In March 2001, Sanofi-Synthelabo Research and Analytical Spectral Devices, Inc. signed a partnership agreement to develop and validate the world's first online near-infrared analyzer for pharmaceutical blister packaging machines. Under the terms of the agreement, ASD would provide the Quality Spec™ TI system (hardware and software), and Sanofi-Synthelabo Research would provide the blister packaging machine and resources to validate the system.
In December, Sanofi-Synthelabo Research started running a QualitySpec TI near-infrared spectroscopy system to inspect blister-packs. In this system, tablets are exposed to near-infrared light, and the light reflected back from the tablets is analyzed. This reflected light contains a positive identification of the tablet, known as an "NIR fingerprint," and provides 100 percent verification of the identity of each tablet. Tests have demonstrated that it can detect a 2 percent concentration in uncoated tablets and a 5 percent concentration in a coated tablet. It can also detect the presence or absence of a compound.
The initial testing and verification of the technology at Sanofi-Synthelabo Research was done on one of the company's active drug products. In this operation, four lanes of blisters are conveyed through a chamber where they are exposed to the near-infrared light. One row of four blisters is analyzed at each cycle. Individual fiberoptic cables transmit the light reflected from each tablet to the analyzer, and if any of the tablets are incorrect, the entire four-tablet grouping is rejected. "The system provides assurance that all of the product is within specifications, not just a representative sample," says a company spokesperson.
One of the features of the system is its easy-to-use "Learn Mode." The computer is put into the learning mode, and a certain number of good samples of the product to be run are sent through the light chamber. Sanofi-Synthelabo Research used 160 tablets (40 rows of four) to train the system. The computer recognizes the "chemical fingerprint" from these samples as the acceptable value, and then rejects any tablets that differ from this standard.
NIR system inspects 2,160 tablets/min
The QualitySpec TI system at Sanofi-Synthelabo Research is installed on a Model EAS unit-dose blister-packaging machine from Klöckner Medipak. In this packaging operation, film is pulled through a forming section, where the cavities for the tablets are formed. The film then passes through manual loading tables, where workers push the tablets into the cavities. The two middle lanes are loaded with pink active tablets at the first tray, while white tablets are pushed into the two outer rows of cavities at the second tray. During the clinical trial, people will take one pink and one white tablet every day, per directions they receive written on the preprinted card to which the blister will be glued.
|The inspection system, above, incorporates a light source, probes, a spectrometer and a computer. A pen marks rows of blisters containing the active component, below.|
The tablets then pass through ASD's QualitySpec TI. The Model EAS is an intermittent-motion machine, so it stops as each row enters the chamber. The fiberoptic cables send light to the spectrometer, and the computer analyzes the light and tells the packaging machine to stop or proceed. The machine runs 40 cycles(160 tablets)/min. After the four-unit grouping exits the chamber, it passes through the top-sealing section, where laminated foil is heat-sealed over the blisters. A colored permanent marker mounted above the line at this point marks the row of blisters containing the active compound. The strips of blisters are then cut into 28-unit packages, which are delivered to a carding machine.
When Sanofi-Synthelabo Research installed the system in December, the first requirement was to "validate" the machine. This is a test to prove that it actually performs as required. Using Learn-Mode, Sanofi-Synthelabo Research ran 40 blister-packs of known product to train the instrument. The company then ran more than 90,000 rows of four tablets each, during which there were 40 challenges (all detected). Some of the challenges included empty cavities and interchanged pink and white products. It found every challenge successfully.
Says Winokur, "By inspecting every tablet, the QualitySpec system helps ensure that every blister has the correct tablet and the correct dosage."
The QualitySpec TI features an evaluation speed of 90 cycles/min, and can evaluate up to 24 tablets simultaneously, giving it the ability to test 2,160 tablets/min. It can also detect up to four different tablets/blisters for multifill applications. In the second phase of the partnership agreement, ASD will develop another QualitySpec TI system for Sanofi-Synthelabo Research's high-volume CP3 blister packaging machine manufactured by Klöckner Medipack.
More information is available:
Inspection system: Analytical Spectral Devices, Inc., 303/444-6825. Circle No. 228.
Packaging machine: Klöckner Medipak, 727/538-4644. Circle No. 229.