Moisture Adsorption and Desorption Properties of Colloidal Silicon Dioxide and Its Impact on Layer Adhesion of a Bilayer Tablet Formulation

Abstract

A bilayer tablet formulation approach was used to develop a fixed dose combination tablet formulation of drugs Y & Z.  The weight of Layer-I containing Drug Y and the weight of Layer -II A or II B containing Drug Z were 250 mg and 1280 mg, respectively.  While layer-I was manufactured using the dry granulation method, Layer -II A and II B were manufactured using the moisture activated dry granulation (MADG) process. Layer II A and Layer II B contained 3% w/w colloidal silicon dioxide with the surface area of 300 m²/g (Aeroperl® -300) and  200 m²/g (Aerosil® -200), respectively, as moisture scavenger , and the rest of the common excipients. Both grades of silicon dioxide were amorphous. The change in grade of silicon dioxide did not alter the compaction behavior of the tablet formulation. When exposed to open 40°C/75%RH for 72 hours, the bilayer tablet consisting of Layers I/Layer II A (containing Aeroperl-300) showed a clear layer separation while tablet consisting of Layers I/Layer II B (containing Aerosil-200) did not. When the individual layer was exposed to similar condition, the water absorption for Layer I, Layer II A, and Layer II B, was 345% w/w, 107% w/w, and 184% w/w, respectively. Thus, the difference in water absorption was higher between Layer I/ Layer II A (containing Aeroperl-300) than Layer I/Layer II B (containing Aerosil-200) leading to more significant shear stress at the layer interface.  The moisture adsorption-desorption isotherms, pore size distributions, mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) for both grades of silicon dioxide suggested that Aeroperl 300 containing small pores (Layer II A) did not retain water while Aerosil 200 (Layer II B) containing large pores did.  It is hypothesized that in spite of its lower surface area, the retained water of Aerosil 200 provided better binding and cohesion to layers, thus minimizing the layer separation.