More efficient preparation of parenteral emulsions or how to improve a pharmaceutical recipe by formulation engineering

Parenteral emulsions are special O/W emulsions used to feed patients whose medical condition makes them unable to eat normally. Therefore, parenteral emulsions must comply with several specifications. One is that the maximum droplet size must be below 5 mu m in order to avoid the risk of a pulmonary embolism. In this work, we describe the step-by-step procedure followed to simplify a current industrial recipe by applying recently developed principles under the name of formulation engineering. Both hydrodynamic and physicochemical formulation parameters were manipulated to reduce energy input and equipment requirements. The current process consists of two heating steps, three mixing stages and filtering to eliminate droplets larger than 5 pm. The mixing stages require first an agitated tank for the making of a coarse dispersion, then a high-speed mixer and last a two-stage homogenizer. Despite the intensive mixing the emulsion does riot comply with droplet size specifications and filtering is necessary. Our procedure requires heating once and then two mixing stages, the first to produce a coarse dispersion and the second to refine droplet size in a conventional agitated tank. Further, no filtering is necessary since no droplets larger than 3 mu m are produced in the mixing tank. The parenteral emulsions resulting of this simplified and less energy intensive process complies with droplet size requirements and are stable over several months. (c) 2004 Elsevier Ltd. All rights reserved.