AUTHOR=Liu DeWen , Yan Huijie , Kong Yiming , You Yun , Li Yanling , Wang Lixin , Tong Yan , Wang Jinyu 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00832

DOI=10.3389/fphar.2018.00832

ISSN=1663-9812

ABSTRACT=<p><bold>Ethno Pharmacological Relevance:</bold> Acetylharpagide is a monomeric compound extracted from <italic>Ajuga decumbens</italic>, widely used for remedying infectious and inflammatory diseases in Southern China.</p><p><bold>Aim of the Study:</bold> 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.</p><p><bold>Materials and Methods:</bold> 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 <italic>in vitro</italic> and <italic>in vivo</italic>. In the <italic>in vitro</italic> tests, the optimized formulation was not released in simulated gastric fluid in 2 h; the release was &lt;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 <italic>in vivo</italic> tests, pharmacokinetic characteristics of the colon-targeted tablets were investigated in dogs.</p><p><bold>Results:</bold> The results indicated that the acetylharpagide tablets with the technology of colon-targeting caused delayed T<sub>max</sub>, prolonged absorption time, lower C<sub>max</sub>, and AUCINF_obs. Meanwhile, the apparent volume of distribution (Vz_F_bs) of the colon-target tablets was higher than the reference.</p><p><bold>Conclusions:</bold> These results suggested that colon-targeted acetylharpagide tablets deliver the drug to the colon. The <italic>in vitro</italic> performance of colon-targeted acetylharpagide tablet was appropriately correlated with its performance <italic>in vivo</italic>.</p>