Reader's response:
Hollow Shaft Sampling With Fiber Optics

Schatz C., Ulmschneider M., Altermatt R., and Marrer S.
Pharmaceutical Quality Control and Quality Assurance, F. Hoffmann-La Roche Ltd., Basel, Switzerland

email for correspondence: caspar.schatz@roche.com

In the Question and Answer section of Dissolution Technologies (November 1999) [1] the final question raised the issue of hollow shaft sampling with fiber optics. The answer explained that the USP Dissolution and Bioavailability Subcommittee was unable to determine whether this technique is USP compliant due to lack of sufficient supporting data. Since considerable effort has been devoted to developing a semi-automated dissolution tester with fiber optics [2, 3] this is a good moment to present the experimental results obtained as preliminary evidence for evaluating fiber optic sampling in the hollow shaft.

All dissolution tests were performed with apparatus 2 (Sotax AT 7 smart, Sotax AG, Allschwil, Switzerland) equipped with hollow shafts and media thermostatted at 37.0 °C as well as degassed by helium sparging or sonication under vacuum [4]. A DAD spectrometer (Tidas II, J & M Analytische Mess- und Regeltechnik GmbH, Aalen, Germany) and a scanning spectrometer (Varian Cary 50, Varian International AG, Zug, Switzerland) were connected to fiber optic probes (Ultra Mini TS 10 mm + 2 LL UV Li/SMA, Hellma GmbH & Co., Müllheim/ Baden, Germany) with pathlengths of 10 mm. As shown in Figure 1, the absorption readings with the fiber optic probes were taken in the vessel in position (B) and in the hollow shaft in position (A). The fiber optical measuring position (B) in the vessel corresponded to the location for manual sampling (C).

System stability was examined by stirring the paddle (50 rpm) with the fiber optic probe in its hollow shaft (A) for 12 hours in deionized water. The identical transmission spectra recorded during the experiment demonstrated the suitability of the arrangement.

The suitability of the hollow shaft sampling was examined with the following procedures.

Using the DAD spectrometer, a method comparison between in situ measurement of the amount of dissolved active substance with fiber optics in the hollow shaft (A) and conventional manual sampling (C), followed by filtration, was performed with six anticoagulant tablets. The fiber optic method used two wavelengths - one to determine the active substance at an absorption maximum and one to correct the baseline offset due to the turbidity from undissolved tablet components [5, 6] - and was validated with regard to linearity (r = 0.99932), precision (RSD = 1.5%) and accuracy (100.4% recovery) [7, 8]. The A(1%, 1 cm) was used for quantification. The mean of 90.1% (± 7.3%) determined by fiber optics in the hollow shaft and the manual sampling mean of 88.8% (± 7.4%) did not differ significantly (p = 95%) [9].

As shown in Figure 1, one anticoagulant tablet dissolution profile was measured with two fiber optic probes in position (A) and (B) simultaneously. In Figure 2 it can be seen that the two sampling positions led to identical profiles.

Figure 1.

Figure 2.

In order to refer to an international standard, dissolution tests with USP calibrator tablets were performed in accordance with Refs. 10 and 11 using the scanning spectrometer. The vessels were stirred at 100 rpm for non-disintegrating tablets and at 50 rpm for disintegrating tablets. Again the amount of dissolved active substance from six tablets per dissolution test was determined by fiber optics in the hollow shaft (A) and manual sampling (C), using a one-point calibration in both cases. For the fiber optical determination of the amount of dissolved substance the two-wavelength method already mentioned was performed. Whereas a validated method was used for the manual sampling [10], only the linearity (r = 0.99950) was verfied for the quantification with fiber optics [8]. The results are shown in Table 1.

Table 1: Results of the dissolution tests performed with USP calibrator tablets

USP dissolution calibrators, non-disintegrating, lot N
Sampling	Mean ± 1 SD [%]	Range [%]
Hollow shaft	19.4 ± 0.4	18.9 ­ 20.1
Manual	19.5 ± 0.6	18.7 ­ 20.4
USP dissolution calibrators, disintegrating, lot L
Sampling	Mean ± 1 SD [%]	Range [%]
Hollow shaft	45.3 ± 1.4	43.2 ­ 47.1
Manual	43.8 ± 2.8	39.2 ­ 45.0

All results lie within the USP acceptance limits of 17­26% for the non-disintegrating type tablets and 38­48% for the disintegrating type tablets and there is no significant difference between manual sampling (C) in the vessel and hollow shaft sampling (A) with fiber optics (p = 95%) [9].
The experiments confirmed that scanning and DAD spectrometers are suitable for measuring the amount of dissolved active substance with fiber optics using the two-wavelength method. It was also shown that sampling with fiber optics in the hollow shaft (A) is equivalent to manual (B) or fiber optic sampling (C) in the vessel. Although only a limited number of experiments was performed, there is strong evidence that sampling by fiber optics in the hollow shaft of apparatus 2 should be regarded as USP compliant.

[1] Mirza T., Question and Answer Section, Dissolution Technologies, 6 (4), 11 (1999)
[2] Aldridge P.K., Kostek L.J., In Situ Fiber Optic Dissolution Analysis, Dissolution Technologies, 2 (4), 10-11 (1995)
[3] Bynum K.C., Kraft E., Pocreva J., Ciurczak E.W., Palermo P., In Situ Dissolution Testing Using a UV Fiber Optic Probe Dissolution System, Dissolution Technologies, 6 (4), 11 (1999)
[4] Rohrs B.R., Stelzer D.J., Deaeration Techniques for Dissolution Media, Dissolution Technologies, 2 (2) 1-9 (1995)
[5] Schatz C., Internal Communication about Soft Gelatin Capsules, F. Hoffmann-La Roche Ltd., Basel (1999)
[6] Schatz C., Internal Communication about Benzodiazepine Tablets, F. Hoffmann-La Roche Ltd., Basel (1999)
[7] International Conference on Harmonization, Validation of Analytical Procedures: Methodology, ICH Harmonized Tripartite Guideline Q2B (1995)
[8] Pharma Switzerland, Quality Assurance and Quality Control, Internal Guideline on Validation of Analytical Methods, F. Hoffmann-La Roche Ltd., Basel (1998)
[9] Doerfel K., Statistik in der analytischen Chemie, Deutscher Verlag für Grundstoffindustrie GmbH, Leipzig (1990)
[10] Pharma Switzerland, Quality Assurance and Quality Control, Internal SOP on Qualification in Dissolution testing, F. Hoffmann-La Roche Ltd., Basel (1999)
[11] The United States Pharmacopeial Convention, Inc., Note on USP Dissolution Calibrator Tablets, Rockville (1997)