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B. Tablet/Capsule Photolysis Cool White Radiation

p^Furosemide Tab (99.6%) ffllFMegestrol Acetate Tab (99.4%) ^Metronidazole Tab (100.2%) Nifedipine Cap (98.4%)

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Furosemide (99.1%)

Figure 2 Summary of tablet and capsule formulation photolysis with UV-A (a) and Cool White (b) radiation. The entries in parentheses are the intralaboratory average.

For powder samples, the presentation of the sample to the photolysis radiation is critical. The powder layer should be thick enough to ensure that no incident radiation is transmitted. Preliminary photolysis studies with nifedipine powder samples indicated that the powder particle size is a significant factor. With a constant total exposed surface area (5 cm diameter Petri dish) and powder layer thickness (2 mm), the extent of nifedipine photodegradation increased as the powder particle size decreased. At a particle size of 250 F (60 mesh) or less, the extent of nifedipine photodegradation remained constant. Apparently, with large particles some incident radiation is transmitted through the powder layer and not absorbed. The drug substance powder samples used in the collaborative study were sized by screening to ensure a particle size of 250 F or less.

3.4 Furosemide Syringe Injection Photolysis

The UV-A and Cool White photolysis results for the furosemide syringe injection formulation with the primary brown plastic wrapper both in place and removed, are presented in Figures 3a and 3b, respectively. The photolysis results for the furosemide drug substance and tablets are included for comparison.

Based on the interlaboratory average, the primary brown plastic wrapper protects the furosemide injection solution from photodecomposition from either UV-A or Cool White radiation. Removing the wrapping produces considerable photodecomposition with Cool White irradiation (32.3% of furosemide decomposed) and extensive photodecomposition with UV-A irradiation (65.3% of furosemide decomposed). All collaborators reported that the injection solution was clear before photolysis but turned a straw brown during photolysis. Some collaborators also noted the formation of a precipitate in the syringe assembly upon photolysis with the brown wrapping removed.

3.5 Metronidazole Injection Photolysis

The UV-A and Cool White photolysis results for the metronidazole injection formulation solution in the plastic IV pouch and in a quartz spectrophotometer cell are presented in Figs. 4a and 4b, respectively. The photolysis results for the metronidazole drug substance and tablets are included for comparison. These results indicate that some photodecomposition occurs with both UV-A and Cool White irradiation whether the formulation remains in the plastic IV pouch or is photolysed in a quartz spectrophotometer cell. Photolysis is more extensive when the formulation solution is photolysed in the quartz spectrophotometer cell, indicating that the plastic IV pouch offers some protection from exposure.

4 CONCLUSION 4.1 Photolysis Apparatus and Quinine Actinometer

Quinine solution as an actinometer system for pharmaceutical photostability studies for the UV-A photolysis was proposed by JPMA. The ICH Expert Working Group has endorsed

A. Furosemide Photolysis UV-A Radiation

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