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 dry granulation, Layer II A and II B were manufactured using a 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, for moisture scavenging, and otherwise common excipients. Both grades of silicon dioxide were amorphous. When exposed to an open relative humidity of 40°C/75% for 72 hours, the bilayer tablet consisting of Layers I/Layer II A (containing Aeroperl® 300) showed a clear layer separation while the tablet consisting of Layers I/Layer II B (containing Aerosil® 200) did not. If the individual layer is exposed to a similar condition, the projected change in the moisture content for Layer I, Layer II A, and Layer II B, could be 63% w/w, 107% w/w, and 109% w/w, respectively. Thus, the difference in moisture adsorption between Layer I/ Layer II A (containing Aeroperl® 300) than Layer I/Layer II B (containing Aerosil® 200) was similar. The comparison of the moisture adsorption-desorption isotherms for Aeroperl® 300 and Aerosil® 200 suggested that Aeroperl® 300 can adsorb relatively large amounts of moisture at any humidity level due to its greater surface area but it does not retain moisture when the humidity decreases. In contrast, Aerosil 200 adsorb relatively smaller amounts of moisture but it retains moisture due to its larger pore sizes. It is hypothesized that the moisture not retained by Aeroperl® 300 could be available for interaction with other Layer I excipients, such as, microcrystalline cellulose and crospovidone. Such interaction can generate significant shear stress at the layer interface triggering the delamination.