INFLUENCE OF PROCESS CONDITIONS ON DRUG-RELEASE FROM PELLETS

The preparation of pellets by the extrusion/spheronization process is widely used. Although a body of work already exists which identifies t he most important factors involved, there are areas of uncertainty sti ll remaining. One of them is the role of water. In addition to the eff ect water has on the physical characteristics of the pellets, some aut hors have also noted that the amount of water required for extrusion c an influence the dissolution profiles achieved with this dosage form. The objective of this work was to study the different ways in which wa ter can be considered an active excipient in terms of the amount used to obtain the wet mass, the dispersion within the mass and the drying process. To achieve this goal, a statistical design was performed, con sidering three levels for the first variable (water content) and two f or both the second (pre-extruser storage time) and third (drying proce ss). Physical characteristics of the pellets were analysed for pellets within the same fraction size of 1-1.4 mm diameter. The analysis indi cated that the amount of water and the extrusion and drying processes are of great importance and influenced the physical characteristics of the resultant pellets. As the analysis of variance procedure indicate s, the influence of the independent variables on the dissolution chara cteristics of AUG, MDT, RDC and cumulative drug release after 12 h are related in a complex manner to the different pellet performances. Hen ce, water should be considered as an 'active' excipient rather than an inert component of the extrusion masses. Copyright (C) 1996 Elsevier Science B.V.