Preparation of Colon-Targeted Acetylharpagide Tablets and its Release Properties in vivo and in vitro

• Main Authors: DeWen Liu, Huijie Yan, Yiming Kong, Yun You, Yanling Li, Lixin Wang, Yan Tong, Jinyu Wang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-08-01
• Series: Frontiers in Pharmacology
• Subjects: colon-targeted tablet; acetylharpagide; release property in vitro; pharmacokinetic characteristics in vivo; in vitro-in vivo correlation
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2018.00832/full

Ethno Pharmacological Relevance: Acetylharpagide is a monomeric compound extracted from Ajuga decumbens, widely used for remedying infectious and inflammatory diseases in Southern China.Aim of the Study: The present study designed and investigated the formulation of colon-targeted acetylharpagide tablets according to the dual controlled release mechanisms of time-delay and pH-sensitivity.Materials and Methods: The core tablets of acetylharpagide were coated with the material used in time-delay systems such as ethyl cellulose and suitable channeling agent, followed by pH-dependent polymers, polyacrylic resin II and III in a combination of 1:4. Furthermore, the release and absorption performance of colon-targets tables were evaluated in vitro and in vivo. In the in vitro tests, the optimized formulation was not released in simulated gastric fluid in 2 h; the release was <5% at pH 6.8 simulated intestinal fluids for 4 h; the drug was completely released within 5 h at pH 7.6 simulated colon fluid. In the in vivo tests, pharmacokinetic characteristics of the colon-targeted tablets were investigated in dogs.Results: The results indicated that the acetylharpagide tablets with the technology of colon-targeting caused delayed Tmax, prolonged absorption time, lower Cmax, and AUCINF_obs. Meanwhile, the apparent volume of distribution (Vz_F_bs) of the colon-target tablets was higher than the reference.Conclusions: These results suggested that colon-targeted acetylharpagide tablets deliver the drug to the colon. The in vitro performance of colon-targeted acetylharpagide tablet was appropriately correlated with its performance in vivo.