(T1030-07-39) Melt Granulation Using a Planetary Triple Mixer for the Metformin Controlled-Release Tablet Containing Ethyl Cellulose and Hydrogenated Vegetable Oil (HVO)

Purpose: The aim of this study is to manufacture, prepare and evaluate the metformin controlled-release tablet containing ethyl cellulose, hydrogenated vegetable oil (HVO), using a planetary triple mixer.

Methods: To prepare the controlled-release granules, a planetary triple mixer (TMG 5, Shinagawa Co., LTD, Japan) was used. Metformin, ethyl cellulose and HVO was poured into bowl of triple mixer. The mixer was operated at temperatures ranging from 80 to 120 ℃ and stirring speeds from 10 to 100 rpm for 10 to 60 minutes. Physical mixtures were also prepared for comparison. After mixing, the flowability of the granules was evaluated using a tap density (PT-TD 300, Pharma Test, Germany). Subsequently, tablets were compressed using hydraulic press manual tableting machine (Handtab, Ichihashi Seiki Co., LTD, Japan). The hardness and dissolution test were then conducted. The dissolution conditions were as follows: medium: hydrochloric acid buffer pH 1.2 according to USP, 900 mL; rpm: 100; temperature: 37 ℃.

Results: Compared to the physical mixture, the granules made by the triple mixer showed several advantages. First, the granules exhibited better flowability than physical mixtures. The melting point of HVO is about 60 ℃, so at 80 to 120 ℃, the HVO was melted and penetrated between the particles, acting as a lubricant. This improved the flowability. Second, the tablets made from the granules showed more controlled-release dissolution profiles. Although the release rates varied for each formulation and sampling time, there was a difference of up to about 30%. This can be attributed to the hydrophobic properties of HVO, which from a hydrophobic matrix that limits the interaction between the drug and water, thereby slowing drug dissolution.

Conclusion: The formulation prepared using the planetary triple mixer demonstrated enhanced flowability and a controlled-release dissolution profile. This method can be applied not only to metformin but also to the manufacturing of controlled-release formulations for other drugs.

Acknowledgements: This research was supported by “Regional Innovation Strategy (RIS)” through the Na-tional Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2021RIS-001), grants funded by the Korean government (NRF-2021R1A2C4002746 and 2017R1A5A2015541), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (HI14C1069).