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Getting Ready to Purchase a Fiber Optics System

Getting Ready to Purchase a Fiber Optics System

Vivian Gray, vagray@rcn.com

John Ballard, ballard@cimquest.com

This feature will be devoted to what to look for when getting ready to purchase a fiber optics system.

John Ballard and I, at the DuPont Pharmaceuticals dissolution R & D lab, evaluated two systems. This was almost a full time commitment on the part of John, as it was his job to fully assess both systems using many products that were already in routine dissolution testing.

Presented here is a checklist we came up with of major equipment parameters to evaluate when examining the various brands. This list is fairly comprehensive, but there may be aspects important to your products and operating procedures that are not covered.

1. Probes

There are different designs of probes: arch, in shaft, in resident, in resident but partially out during sampling. The probe design does appear to be stabilizing although it looks like the vendors are constantly revisiting it in response to customers.

a. Available pathlengths. Watch for availability of small pathlength cells, fiber optic probes may not be able to get down to the smaller cell pathlength that are found with UV flow-cells.

b.Size and Shape. Is the probe container the size of a cannula or smaller, where does the cell attach? Some are arch-shape–how thin and durable is the wire?

c.Orientation of the probe. Is it put through the vessel cover or on a manifold? Is it located in the USP stated sampling zone? Which is “..From zone midway between the surface of the Dissolution Medium and the top of the rotating basket of blade, not less than 1 cm from the vessel wall” (3).

d.Location of probe throughout the test. A question with conventional automated sampling that always needs to be considered is whether the sampling probes are in the dissolution medium throughout the test or just when the sample is taken. With Fiber optics probes it is quite difficult to completely take the probe out, hence risk the cell drying out. Evaluate the effect of the probe doing the proper validation—this will be described in the next topic of validation.

e.Cleaning procedure. What is the best way to clean the fiber optic probe? How do you assess carryover? Do you use a water/methanol rinse? How much volume of each? How do you dry the probe? How do you store the probe?

f.Handling ease. How breakable/delicate are the cells? Ease of cable and probe manipulation, and of replacing cells should be examined.

2. Optic System Design

Some designs have each probe as a different spectrophotometer with six individual photodiode arrays (PDAs), whereas others are sequentially related to one central spectrophotometer using a channel selector reads from each vessel serially. This design has a large impact on data collection, especially timing of sampling and zero readings. The pro and cons of the spectrometric operational differences should be understood. How is the light scattering accommodated? These different designs have an impact of the operation also as seen in 3. Operation.

3. Operation

a.Are air bubbles a problem? Always deaerate the medium the help alleviate this issue. Even after deaeration, before the analysis begins but after the probes are in the medium, you must be sure to lightly tap the fiber optic probes to insure that no air bubbles have been caught in the cell within the probes.

b. Assess the reproducibility and precision of the standard readings, looking at each probe versus between probes. This is where the different optic design systems may become a factor.

c.How are the standards read? In a common beaker? How easy is it to read the standards? It is difficult if not impossible to bracket the standards after each timepoint as in conventional reading, therefore the running of standards at the beginning and end of the run is necessary.

d. How do you mechanically set up a run, what is the compatibility with different bath models, how about sample introduction (staggered or simultaneously), can the bath operation be controlled, is there dual bath control, and how easy is the cleanup of the entire system?

e.Capacity to perform and sample an infinity (fast stir) timepoint.

4. Data collection

Some systems will have baseline correction only; others have both baseline correction and second derivative. These are mathematical, computer generated ways to compensate and accommodate the turbidity and light scattering caused by excipients or undissolved drug. This aspect of the fiber optic technology is the most important. Validation will be a major factor in determining the usefulness of these mechanisms.

a.Final calculation reporting- % dissolved and/or mg dissolved?

b.Graphic printing capabilities-% dissolved, individual scans, per channel?

c.Report format: how versatile?

d.Compatibility with a LIMS system. It is very important to understand and be sure to get the companies other groups (IT) involved.

e.What is the true absorbance range versus suggested range by the vendor?

5.Evaluate

Evaluate cost and cost of parts and different cell sizes. Assess the technical support. Is it worthwhile to retrofit to existing equipment? If you go through all these parameters with your vendor and hopefully have hands on experience with the equipment ; you will be very well equipped to make a good decision.

I have also included for your information a bibliography of many articles that have been written on fiber optics. It is comprehensive, but if I have left any good articles out, please let the website know and it will be added.

Bibliography

(1)Earnhardt J, Nir I. Fiberoptic dissolution testing, Advances, drug quality control, Spectroscopy 2000:15(2): 31-38.

(2)Cho JH, Gemperline PJ, Salt A, Walker DS. UV/Visible Spectral Dissolution Monitoring by in Situ Fiber-Optic Probes, Analytical Chemistry 1995:67(17): 2858-2863.

(3)Li W, Chen J, Xiang B, An D. Simultaneous on-line dissolution monitoring of multicomponent solid preparations containing vitamins B1, B2, and B6 by fiber-optic sensor system, Analytica Chimica Acta 2000:408(2000): 39-47.

(4)Bynum, KC, Kraft E, Pocreva J, Ciurczak EW, Palermo P. In Situ Dissolution Testing Using A UV Fiber Optic Probe Dissolution System, Dissolution Technologies 1999:6(4): 8-10.

(5)Johansson J, Cauchi M, Sungren M. Multiple fiber-optic dual-beam UV/Vis system with application to dissolution testing, Journal of Pharmaceutical and Biomedical Analysis:2002:29 (3):469-476.

(6)Inman GW, Wethington E, Baughman E, Horton M, System optimization for in situ fiber-optic dissolution testing, Pharmaceutical Technology: October 2001: 92-100.

(7)Bynum KC, Kraft E, A new technique in dissolution testing, Pharmaceutical Technology: 23 (10): 1999.

(8)Dubin CH, Presto dissolvo! Fiber otic dissolution: Magical results? Pharmaceutical Formulation and Quality: Aug./Sept 2002: 20-27.

(9)Bynum K, Roinestad K, Kassis A, Pocreva J, Gehriein L, Cheng F, Palermo P, Analytical Performance of a fiber optic probe dissolution system, Dissolution Technologies: 6 (4): 2001:13-22.

(10)Schatz C, Ulmschneider M, Altermatt R, Marrer S, Evaluation of the Rainbow dynamic dissolution monitor semi-automatic fiber optic dissolution tester, Dissolution Technologies: 7 (4): 2000:8-17.

(11)Schatz c, Ulmschneider M, Altermatt R, Marrer S, Reader’s response: hollow shaft sampling with fiber optics, Dissolution Technologies: 7 (1): 2000: 20-21.

(12)Allen RI, Box KJ, Comer JEA, Peake C, Tam KY, Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs, Journal of Pharmaceutical and Biomedical Analysis: 17(1998): 699-713.

(13)Josefson M, Johansson E, Torstensson A, Optical fiber spectrometry in turbid solutions by multivariate calibration applied to tablet dissolution testing, Anal Chem: 60 (1988): 2666-2671.

(14)Gemperline PJ, Cho JH, Baker B, Batchelor B, Walker DS, Determination of multicomponent dissolution profiles of pharmaceutical products by in situ fiber-optic UV measurements, Analytica Chimica Acta: 345 (1997): 155-159.

(15)Li W, Chen J, Xiang B, An D, Simultaneous on-line dissolution monitoring of multicomponent solid preparations containing vitamins B1, B2 and B6 by fiber-optic sensor system, Analytica Chimica Acta: 408 (2000):39-41.

(16)Nir I, Johnson BD, Johansson J, Schatz C, Application of fiber-optic dissolution testing for actual products, Pharmaceutical Technology: May (2001): 33-40.

(17)Rogers P, Hailey PA, Johnson GA, Dight VA, Read C, Shingler A, Savage P, Roche T, Mondry J, A comprehensive and flexible approach to the automated-dissolution testing of pharmaceutical drug products incorporating direct UV-Vis fiber-optic analysis, on-line fluorescence analysis and off-line storage options, LRA: 12 (2000): 12-22.

(18)Schatz C, Ulmschneider M, Altermatt R, Marrer S, Altorfer H, Manual in situ fiber optic dissolution analysis in quality control, Dissolution Technologies: 7(2): 2000: 6-13.

(19)Gray V, Ballard J, Dissolution Testing Using Fiber Optics – A Regulatory Perspective, American Pharmaceutical Review, submitted for publication March 15, 2003.

(20)Aldridge PIKE, Melvin DEW, Williams BA, Brain K, Kostek JL, Sekulic SS. A Robotic Dissolution System with On-Line Fiber Optic UV Analysis. Journal of Pharmaceutical Sciences 1995:84 (8) 909-914.

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