Development of matrix-based theophylline sustained-release microtablets

Microtablets containing high theophylline content (from 60% to 80%) based o n a Eudragit RS PO matrix were produced on a rotary tablet press. The influ ence of the compaction pressure, the plasticizer content used for the granu lation of theophylline particles, and the amount of theophylline on the dru g release were investigated. The effects of surface area and the addition o f magnesium stearate as a hydrophobic agent on the drug release were studie d. The storage stabilities of the release rate at room temperature and at 5 0 degrees C were also determined. Dissolution profiles expressed as percent age of theophylline dissolved were obtained over 8 hr in 900 ml of purified water at 37 degrees C and 75 rpm. It was observed that the compaction pres sure (from 200 MPa to 250 MPa) had no effect on the theophylline release. T he use of triethyl citrate (TEC) as a plasticizer in the granulation of the ophylline enhanced the physical properties of the microtablets. Theophyllin e content in the range 60% to 80% did not affect the drug release. The theo phylline release obtained was a function of the quotient surface area/table t weight and therefore was dependent on the tablet diameter. To reduce the dissolution rates, magnesium stearate was added in a concentration up to 50 % of the matrix material. Tablets of this hydrophobic formulation fulfilled the requirements of USP 23 for theophylline sustained-release preparations . Storage at room temperature for 3 months and at 50 degrees C for 2 months showed no significant influence on the theophylline release.