Further enhancement of the sustained-release properties and stability of direct compression gel matrix bilayer tablets by controlling the particle size of HPMC and drug microencapsulation

The Theophylline and Salbutamol Bilayer Sustained-release Tablets (Yi Xi Qing (R)), prepared via wet granulation, discolor during long-term storage, and the process is less reproducible and more cumbersome. In this study, the direct compression (DC) method was used to prepare equivalent and stable theophylline-salbutamol bilayer sustained-release (TBS) tablets, using Yi Xi Qing (R) as a reference formulation (the relative bioavailabilities for theophylline and salbutamol were 96.3 % and 103.9 %, respectively, with release similarity factors of 60.12 and 80.99). Lipid microencapsulation of salbutamol via hot-melt extrusion (HME) and the use of HPMC with a particle size of less than 96.55 mu m (D90) in the theophylline layer enhanced the stability of salbutamol during long-term storage and controlled the release of theophylline from a minimal amount of gel matrix material, respectively. The results of this study may offer insights into the preparation of DC hydrophilic gel matrix bilayer tablets with high drug loading capacity.