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Abstract
Sustained Release for St. John?s Wort: A Rational Idea?
Lucia Disch, Kristina Forsch, Beate Siewert, Jürgen Drewe and Gert Fricker
Purpose: Aim of this study was to evaluate St. John’s wort (SJW) extract for its suitability to be formulated in a sustained release dosage form using Ze 117 as example extract.
Methods: Hypericin as marker for naphtodianthrones and quercetin as marker for contained flavonoids in Ze 117 were evaluated for solubility through shake flask method and for in vitro permeability through Caco-2 monolayers. Furthermore, different intestinal segments were screened for absorption capacity of markers using an in situ rat model.
Results: Over a physiological pH range, naphthodianthrones exhibited pH-dependent solubility profiles with best solubility at pH 6.8. In contrast, solubility of flavonoids was pH-independent. In Caco-2 monolayer system, low permeation was evident for naphthodianthrone hypericin, while the flavonoid quercetin showed high permeation. Results of in situ rat model showed absorption of hypericin and quercetin mainly in jejunum.
Conclusion: SJW extract covers components with different physicochemical properties. Predominant absorption in rat intestinal segments indicated presence of an absorption window in small intestine. Furthermore, there is high drug concentration per single dose in combination with a complex extract mixture. Thus, development of a sustained release formulation for SJW extract is challenging.