Purpose: Although there have been numerous studies for enhanced gastroretention (GR), many of the mechanisms could not prove the in vivo efficacy and safety, showed difficulty in formulation development and lacked manufacturability. Although the products using swelling or floating mechanisms are approved by regulatory agencies, clinically approved swellable polymers are also known for their release-sustaining effects, limiting their use in conventional gastroretentive dosage forms. Hence, a novel tablet design that separates gastroretentive ability (e.g., swelling and floating) and dissolution profiles will enable wide application of the gastroretentive drug delivery system (GRDDS) to the existing drugs. The aims of this study were to prepare a porous bilayer tablet composed of drug layer and GR layer, and to evaluate its in vitro gastroretentive properties as well as its ability to modify drug release profiles.
Methods: Highly porous bilayer tablets containing ranitidine as a model drug were prepared using direct compression of drug layer and GR layer, followed by sublimation of volatile material. First, the drug layer was composed of the model drug, fillers and HPMC 4,000, a sustained-release agent. The GR layer was composed of a volatile material, camphor and a swellable agent, PEO 7M. The powder mix was compressed into bilayer tablets with various ratio of HPMC in the drug layer (15%, 30%, and 50% w/w) and vacuum-dried at 60oC. The internal structures of the bilayer tablets were analyzed with X-ray tomography. The single layer tablets with components of GR layer and drug layer combined are also prepared. The in vitro dissolution test was conducted for 12 h using paddle method in pH 1.2 buffer solution. The tablets were also analyzed for their swelling profiles in the same dissolution media.
Results: The prepared tablets could float immediately above the dissolution media with the drug layer submerged until the end of testing. This is due to the differences in porosity of the GR layer and the drug layer as shown in the X-ray tomography. The radial swelling of the GR layers was not affected by the HPMC content of the drug layer. Furthermore, the dissolution of the drug layer could be modified with the HPMC content. On the contrary, the release rates of single layer tablets were lower than bilayer tablets and unaffected by the HPMC content, which was expected as the highly swellable polymer in the GR layer, PEO, is known for its sustained release behavior. This indicates that the separation of the GR layer and the drug layer can maintain high swelling ability while enabling the formulator to modify the release profile.
Conclusion: The prepared bilayer tablets showed high swelling and floating properties without delaying the dissolution profiles, indicating the system is able to harness the GR property to the maximum extent. Separation of the GR components (floating and swelling) and the drug into two layers enabled easier formulation development as the composition of the GR layer could be kept the same while changing the composition of the drug layer. Furthermore, the prepared system only requires bilayer tablet compression and vaccum-drying for manufacturing, which further increases the applicability of the system.
Kyu-Mok Hwang
– Postdoctoral Researcher, Sungkyunkwan University, Suwon-si, Gyeonggi_doKyu-Mok Hwang
– Postdoctoral Researcher, Sungkyunkwan University, Suwon-si, Gyeonggi_doThi-Tram Nguyen
– Sungkyunkwan UniversityCheol-Hee Cho
– Sungkyunkwan UniversityKyu-Min Hwang
– Mr., Sungkyunkwan University, SUWON-SIHyeong-Seok Choi
– Sungkyunkwan UniversityJae-Hyeok Im
– Sungkyunkwan UniversityHye-Ryeong Park
– Sungkyunkwan UniversityEun-Seok Park
– Sungkyunkwan UniversityKyu Mok Hwang
– Sungkyunkwan University, Suwon-si, Gyeonggi_do381 Views