Evolution of structure and properties of granules containing microcrystalline cellulose and polyvinylpyrrolidone during high-shear wet granulation.
Granulation behavior of microcrystalline cellulose (MCC) in the presence of 2.5% polyvinylpyrrolidone (PVP) was systematically studied. Complex changes in flowability and tabletability of lubricated MCC granules are correlated to changes in intragranular porosity, morphology, surface smoothness, size distribution, and specific surface area (SSA). With 2.5% PVP, the use of 45% granulation water leads to 84% reduction in tablet tensile strength and 76% improvement in powder flow factor. The changes in powder performance are explained by granule densification and surface smoothing. The granulating water level corresponding to the onset of overgranulation, 45%, is significantly lower than the 70% water required for unlubricated MCC granules without PVP. At more than 45% water levels, MCC-PVP granules flow well but cannot be compressed into intact tablets. Such changes in powder performance correspond to the rapid growth into large and dense spheres with smooth surface. Compared with MCC alone, the onset of the phase of fast granule size enlargement occurs at a lower water level when 2.5% PVP is used. Although the use of 2.5% PVP hastens granule nucleation and growth rate, the mechanisms of overgranulation are the same, that is, size enlargement, granule densification, surface smoothing, and particle rounding in both systems.
Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455.
Frederick
F
Osei-Yeboah
Yushi
Y
Feng
Changquan Calvin
CC
Sun
D002482:Cellulose / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength; D014867:Water / Q000737:chemistry
D011208:Powders; D013607:Tablets; D014867:Water; D002482:Cellulose; D011205:Povidone; C109691:microcrystalline cellulose
compaction; excipients; formulation; granulation; mechanical properties; oral drug delivery; particle engineering; powder flow; powder technology; tableting