Moisture adsorption and desorption properties of colloidal silicon dioxide and its impact on layer adhesion of a bilayer tablet formulation

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

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Acid-Catalyzed Hydrolysis of BMS-582664: Degradation Product Identification and Mechanism Elucidation

BMS-582664 is an investigational drug intended for cancer treatment through oral administration. The preformulation studies revealed two unexpected degradation products under acidic conditions by reversed-phase high-performance liquid chromatography with ultraviolet detection. Additional liquid chromatography–mass spectrometry results suggested that these were cleavage (hydrolysis) products of a diaryl ether. To further understand the degradation mechanism, the reaction was carried out in 18O-labeled water. The 18O was found to be incorporated in only one of the two hydrolysis products. The results suggest that the corresponding α carbon in the heterocycle was unusually eletrophilic in acidic conditions probably because of the protonation of the neighboring nitrogen. This led to the selective attack by water and the consequent hydrolysis products. The study provides a new example of hydrolytic degradation of pharmaceutical compounds, and the reaction center is an aromatic heterocyclic carbon with an aryloxy substitution. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3526–3530, 201