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 their 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.

Influence of spray nozzle aperture during high shear wet granulation on granule properties and its compression attributes.

The distribution of granulating liquid is known to affect the high shear wet granulation process but the impact of the spray nozzle attributes is still unclear. While homogenous liquid distribution can be achieved by using a spray nozzle, the effect of different nozzle aperture sizes on granule properties is not well understood. In this study, nozzles of different aperture sizes were used to introduce the granulating liquid in high shear wet granulation using different process parameters. Design of experiment approach was utilised to assess effect of process parameters on granule properties. Granules produced with different spray nozzles were evaluated for binder distribution inhomogeneity, size, shape, flowability and compression attributes such as tabletability and yield pressure. Coarser granules with better flow properties were produced using the smaller aperture size nozzle. On the other hand, granules had better tabletability and lower yield pressure when larger aperture size nozzle was used. Furthermore, size of granules produced by using larger aperture size nozzle was more affected by changes in the process variables which could be influenced by the differences in granulating liquid feed rate and spray droplet size. Although the granules aspect ratios were comparable across the nozzle aperture sizes, granules produced from smaller aperture size nozzle appeared to be rounder. Regardless of the nozzle aperture sizes, homogenous binder distribution was achieved. The findings from this study could be a useful guide to the selection of the appropriate nozzle aperture size in wet granulation.