Purpose: The aims of this study were to prepare colon-targeted lipase releasing microparticles and evaluate the hydrolysis of dietary triglycerides in artificial steatorrhea. Orlistat (also known as the brand name, XENICAL™) is a potent inhibitor of gastrointestinal lipases that are responsible for breaking down ingested fat. The unabsorbed fats make runny stool, diarrhea, and foul-smelling stool known as steatorrhea and it decreases the patient compliance as unpleasant gastrointestinal side effects. The targeted delivery of lipase to colon has a possibility to decrease the side effect of the drug without affecting the orlistat action. For the effect of colon-targeted lipase releasing microparticles, in-vitro test was performed in artificial steatorrhea with similar colon condition.
Methods: The artificial steatorrhea was prepared with artificial feces and olive oil. Artificial feces were manufactured with corn starch, gelatin, and fumed silica. They were mixed by manual method and was kneaded with phosphate buffer. Olive oil 2.4 g instead of fats was added to 30 g of prepared feces. The different lipase amount with same orlistat and bile acid amount was injected in the artificial steatorrhea.
It was incubated in water bath for 30 hours at 37°C, 50 rpm. They were centrifuged at 1500 rpm for 5min and measured the thickness of the supernatant as olive oil amount. The viscosity of them was evaluated by the viscometer. Colon-targeted lipase releasing microparticles were prepared by using the enteric coating polymer and the proposed tablet was prepared with orlistat and colon-targeted lipase releasing microparticles.
Results: The thickness measurement results showed that the presence of lipase decreased the thickness of oil layer. More shallow thickness was observed with more lipase. It showed that the olive oil was decreased and digested by the lipase. The viscosity results measured by viscometer presented that the prepared steatorrhea without lipase was about 5000 cp of viscosity and the steatorrhea with the lipase was observed as about between 600 and 1500 cp. It was expected that the viscosity was dominated by viscosity of the solid component in the steatorrhea without lipase due to separation between oil and the feces. In the steatorrhea with lipase, fatty acid and glycerol degraded by lipase from fat, increased the mixing with between oil and feces which has high water content. So, they were observed the low viscosity compared with the steatorrhea without lipase. The prepared orlistat tablet showed the similar dissolution profiles with comparator and lipase release in the condition of colon.
Conclusion: The lipase presence in artificial steatorrhea decreased viscosity due to improved mixing degree between digested oil and feces. That showed that the possibility of the colon targeted lipase can decrease side effect of the orlistat like the steatorrhea. The prepared orlistat tablets containing the colon targeted lipase releasing microparticles are expected that improve the patient compliance due to decreasing the steatorrhea.
Seong-Jun Park– Chungbuk National University, cheongju-si, Ch'ungch'ong-bukto
Dong-Wook Kim– Cheongju University, cheongju-si, Cholla-bukto
Chun-Woong Park– Chungbuk National University, cheongju-si, Ch'ungch'ong-bukto