Spheronisation mechanism of MCC II-based pellets

Abstract

Abstract Microcrystalline cellulose II (MCC II) – a polymorph of commonly used MCC I – was introduced as new pelletisation aid in wet-extrusion/spheronisation. Preliminary investigations suggested that the spheronisation mechanism of MCC II-based pellets differs from the known mechanism of MCC I. Therefore the spheronisation mechanism of MCC II-based pellets was investigated and compared to that of MCC I. The study dealt with the effect of spheroniser load as well as spheronisation speed and time on the pellet properties of shape (aspect ratio), size (equivalent diameter), weight, porosity, size distribution (10%-interval) and yield (fine fraction) of MCC II-based formulations. The parameters were systematically varied in a 3 3 full factorial design; Furthermore spheronisation time experiments with spheronisation times from 10 s to 15 min (13 steps) were conducted. For this purpose mixtures with 20% MCC II and 80% lactose or chloramphenicol were chosen. A mixture of 20% MCC I and 80% lactose served as comparison. Regarding the MCC II-based pellets all investigated pellet properties were significantly influenced by spheronisation speed and time, spheroniser load showed nearly no influence. Aspect ratio, 10%-interval and porosity decreased continuously throughout the entire spheronisation process. After a slight decrease, pellet weight and equivalent diameter increased during spheronisation. On the contrary the fine fraction decreased during spheronisation after passing a maximum in the first minutes of spheronisation. MCC I-based pellets behaved differently during spheronisation: Pellet weight remained nearly constant during spheronisation and the equivalent diameter decreased; The fine fraction was lower compared to that of the MCC II-based pellets. The higher fine fraction of MCC II could partly explain this result as the fine fraction layered on the pellets. However, the fine fraction was too low to explain the complete weight gain. Therefore, a new spheronisation mechanism for MCC-II based pellets was proposed: It was suspected that small pellets abraded during processing and layered on the other pellets. This presumption was supported by the high increase of the 10%-interval of the MCC II-based pellets during spheronisation indicating a narrowing of the size distribution; The improvement was less pronounced for the MCC I-based pellets. MCC II behaves in a different manner than MCC I in spheronisation: A deeper insight into the spheronisation of MCC II-based pellets was obtained providing a new pelletisation mechanism that is the basis to control and influence the spheronisation process of MCC II-based pellets.