How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.
This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetsstr. 1, Duesseldorf 40225, Germany.
Robin
R
Meier
Novartis AG, Basel 4002, Switzerland.
Klaus-Peter
KP
Moll
Novartis AG, Basel 4002, Switzerland.
Markus
M
Krumme
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetsstr. 1, Duesseldorf 40225, Germany. Electronic address: Kleinebudde@hhu.de.
Peter
P
Kleinebudde
D019245:Compressive Strength; D004339:Drug Compounding / Q000379:methods*; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
D010592:Pharmaceutic Aids; D004364:Pharmaceutical Preparations; D013607:Tablets; D011205:Povidone
compaction; formulation; granulation; porosity; tableting