Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions

Publication date: 5 April 2018 Source:International Journal of Pharmaceutics, Volume 540, Issues 1–2 Author(s): Toshiro Sakai, Daiki Hirai, Shin-ichiro Kimura, Yasunori Iwao, Shigeru Itai The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone–vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes–Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid–liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research