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Stability and Stabilization of Hyperforin

Harald C. J. Orth and Peter C. Schmidt

Eberhard-Karl-University of Tübingen, Department of Pharmaceutical Technology, Tübingen (Germany)

Herrn Prof. Dr. Bernhard C. Lippold zum 60. Geburtstag gewidmet

Stabilität und Stabilisierung von Hyperforin

Hyperforin as one of the main components of Hypericum perforatum L. amounts from 2 to 4 % of the composition of the dried herb. Recent pharmacological and clinical studies focus on hyperforin as the main active ingredient. Marketed preparations are widely used in the therapy of mild to moderate depressive disorders. Hence, in this work the stability in solution and the stabilization in the solid state in the presence of additives have been investigated. Hyperforin and adhyperforin in solution showed similar stability profiles. Since degradation was accelerated by light, exclusion of light for the improvement of stability is recommended. In solution, the substances were found to be more and more destabilized as polarity of the medium decreased. In methanol/water, after 30 days of storage at 20 °C only 19 % degradation occurred while in n-hexane a degradation of 97 % after 24 h was observed. The influence of pH and daylight exposure was evident. Acidified methanolic solution showed more stabilizing effect than a methanolic solution alone. In a basic methanolic solution the substances were completely decomposed. The effect on the stability of the substance was not apparent when exposed to light. Stabilization in the solid state with antioxidants was achieved with the addition of 1 % ascorbic acid together with 0.1 % citric acid which was superior compared to ascorbic acid alone. Sodium bisulfite, DL-a -tocopherol as well as a solid dispersion with polyethylene glycol 6000 did not show any significant stabilizing effect. A silica gel matrix with a loading of 0.1 % hyperforin had a good stability. Higher contents of hyperforin were not possible. Inclusion complexes with a-, ß -, 1.8methyl-ß -and g-cyclodextrin affected the stability in totally different ways. On the one hand, a-cyclodextrin catalyzed the degradation of hyperforin. On the other hand, 1.8methyl-ß -cyclodextrin resulted in only 2.5 % degradation after 6 months at 20 °C showing an excellent stabilizing effect. Thus a long-term storage at room temperature with 1.8-methyl-ß -cyclodextrin-complex is possible.

Key words Adhyperforin · Hyperforin, light sensitivity, stability in solution, stabilization · 1.8-Methyl-ß--cyclodextrin