[Dosage problems in suspension eyedrops].

PURPOSE

In opthalmic suspensions, the mean dose and the uniformity of amounts administered in single drops depend upon the redispersibility of drug particles by shaking. The present article is a contribution to the development of the experimental and theoretical basis for a reproducible test, by which the dose uniformity of suspension eyedrops can be assessed under therapeutically relevant conditions. The requirement that suspension eyedrops and similar dosage forms should be redispersable after sedimentation upon storage is stated in the monographs on eyedrops of the German Pharmacopoeia and can be found in similar contexts in other pharmacopoeias. Until now, however, no corresponding test method has been specified.

METHODS

Shaking profiles were recorded in 31 subjects and 27 patients using an acceleration sensor. They were compared with the acceleration profile of a computer-controlled pneumatic shaker and sampler. Both frequency and intensity of the shaking action were quantified by Fourier analysis of the acceleration profiles. The drug content of single drops of Isopto-dex (0.1% dexamethasone), Chibro-Amuno 3 (1% indomethacin), and Inflanefran-forte (1% prednisolone acetate) was assessed exhaustively in four 5-ml specimens of each ophthalmic suspension using the apparatus. The dose uniformity of single drops of suspension eyedrops was measured by UV-spectrophotometry for the entire contents of bottles. Four samples per day were drawn after six shaking cycles for approximately 4 weeks with three intervals of 4 h during daytime and 1 interval of 12 h during the night.

RESULTS

The shaking intensity of patients was lower than that of healthy subjects, while the frequency was similar for both groups. The intensity of the apparatus corresponds to the 67th percentile of the patients and to the 18th percentile of the healthy subjects. It was sufficiently close to the central values of both distributions to allow comparisons. for Isopto-dex, the mean drug content of 9.5 microns per drop amounted to only 25% of the value expected after complete redispersion, with a coefficient of variation (CV) of 23%. The mean value for Chibro-Amuno 3 was 93% of the expected quantity of indomethacin with a CV of 34%, while the mean content of Inflanefran-forte drops was 95% of the labelled dose with a CV as low as 9%.

CONCLUSION

The drug content of single drops of ophthalmic suspensions can be studied under well-defined and reproducible conditions by means of a computer-controlled pneumatic shaking and sampling apparatus. Under the conditions prevailing in this study, the solidified sediment of Isopto-dex was incompletely redispersed, so that doses were significantly too low. A variable dosing pattern with acceptable mean was observed for Chibro-Amuno 3, while the results for Inflanefran-forte were fully satisfactory.