Fibrillated Cellulose via High Pressure Homogenization: Analysis and Application for Orodispersible Films.

Abstract

Powdered cellulose (PC) and microcrystalline cellulose (MCC) are common excipients in pharmaceuticals. Recent investigations imply that particle size is the most critical parameter for the different performance in many processes. High-pressure homogenization (HPH) was used to reduce fiber size of both grades. The effect of the homogenization parameters on suspension viscosity, particle size, and mechanical properties of casted films was investigated. PC suspensions showed higher apparent viscosities and yield stresses under the same process conditions than MCC. SLS reduced shear viscosity and thixotropic behavior of both cellulose grades probably due to increased electrostatic repulsion. Homogenization reduced cellulose particle sizes, but re-agglomeration was too strong to analyze the particle size correctly. MCC films showed a tensile strength of up to 16.0MPa and PC films up to 4.1MPa. PC films disintegrated within 30s whereas MCC films did not. Mixtures of MCC and PC led to more stable films than PC alone, but these films did not disintegrate anymore. Diclofenac sodium was incorporated in therapeutic dose with drug load of 47% into orodispersible PC films. The content uniformity of these films fulfilled requirements of Ph.Eur and the films disintegrated in 12s. In summary, PC and MCC showed comparable results after HPH and most differences could be explained by the smaller particle size of MCC suspensions. These results confirm the hypothesis that mainly the fiber size during processing is responsible for the existing differences of MCC and PC in pharmaceutical process, e.g., wet-extrusion/spheronization.