In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

Jeong Soo Kim,1 Kwang Ho Cha,1 Seung Yeob Kang,1 Donghan Won,1 Sun Woo Jang,1 Miwon Son,1 Moon Ho Son,1 Ho Jung Choi,2 Young Won Lee,2 Myung Joo Kang3 1Dong-A Pharmaceutical Co. Ltd., Giheung-gu, Yongin, Gyeonggi, 2College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungnam National University, Daejeon, 3College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, South Korea Objective: DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601.Method: In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days.Results: Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm3) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy.Conclusion: Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. Keywords: DA-9601, gastroretentive tablet, controlled release, radiographic studies, gastroprotective effect