Manufacture and in vitro characterization of a new liquid theophylline sustained release dosage form - Sachets with microcapsules for the preparation of a ready-to-use sustained release suspension

The administration of currently available theophylline (CAS 58-55-9) sustained release preparations with high drug doses (hard capsules, tablets) presents difficulties for certain patient groups as children and elderly, due to the large geometry of these dosage forms. Therefore, a suspension for easy administration based on the novel Liquitard(R) technology was developed using theophylline microcapsules. This paper describes the manufacturing procedure of the new dosage form and its in vitro release characteristics as a function of various parameters. During manufacturing, the suspension-forming excipients are first granulated and then filled into sachets together with the microcapsules. The sustained release suspension is prepared by the patient himself immediately before administration. The in vitro release of theophylline from the dosage form is neither affected by the suspension-forming excipients nor by the drug amount. This allows for the manufacture of sachets with different drug strength maintaining the same qualitative composition. Furthermore, the in vitro release is independent of pH, osmolality, agitation and of the addition of surfactants and native bile to the dissolution medium. The new dosage form thus meets the current EC-guidelines for oral sustained release dosage forms. The in vitro limits of the dissolution testing were verified on the basis of the bioequivalence of the batches at the upper and lower specification limits.