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

• Published in: International journal of pharmaceutics Vol. 540; no. 1-2; pp. 171 - 177
• Main Authors: Sakai, Toshiro, Hirai, Daiki, Kimura, Shin-ichiro, Iwao, Yasunori, Itai, Shigeru
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.04.2018
• Subjects: Amorphous solid dispersion; Copovidone; Dissolution model; Melt extrusion; Polyvinylpyrrolidone; Solid–liquid interface; Amorphous solid dispersion; Solid–liquid interface; Polyvinylpyrrolidone; Dissolution model; Copovidone; Melt extrusion
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.02.013

[Display omitted] 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 tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation.