Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC–mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC–mannitol, and respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance.

It was found that co-processed HPMC–mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150–200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC–mannitol ratios. Co-processed HPMC–mannitol offers an interesting addition to the formulator’s toolbox in the design of controlled release formulations for direct compression.

Materials

Direct compression grade HPMC (HPMC DC; METHOCEL™ DC2 K4M, HPMC 2208, 4000 mPa.s grade, Colorcon, USA) and co-processed HPMC–mannitol (mannitol CR-H, PEARLITOL® CR-H, Roquette, France) were used as received. HPMC–mannitol co-processed samples of various ratios (i.e., HPMC:mannitol 70:30, 50:50, and 20:80 which corresponded to H70M30–CP, H50M50–CP, and H20M80–CP, respectively) were manufactured by Roquette, France, where mannitol syrup was sprayed onto fluidized HPMC particles (Benecel™ K4M CR, Ashland).

Christina Yong Xin Kang, Wen Chin Foo, Kwan Hang Lam, Keat Theng Chow, Yuan Siang Lui, Hui Ping Goh, Antoine Salome, Baptiste Boit, Philippe Lefevre, Tze Ning Hiew, Rajeev Gokhale, Paul Wan Sia Heng, Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient, International Journal of Pharmaceutics, 2024, 124298, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124298.