Janez Ržen, David Senica, Matjaž Uštar, Pavel Drnovšek, Stojan Kogej
LEK d.d., Pharmaceutical and Chemical Company, Verovškova 57, 1526 Ljubljana, Slovenia
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva, 1000 Ljubljana, Slovenia
Angiotensin-converting enzyme (ACE) inhibitor lisinopril is an active pharmaceutical ingredient produced through a stepwise chemical synthesis. After the synthesis lisinopril is purified by a low pressure liquid chromatography. A polar, water-based mobile phase is used as an eluens. Purified lisinopril is precipitated from the concentrated chromatography main fractions which are presently concentrated to a specified lisinopril concentration in a simple, single stage vacuum evaporator. Evaporation of large volumes of water is not economical and as an alternative solution a reverse osmosis can be used. A suitability of the reverse osmosis for concentrating the main fractions from the lisinopril chromatography was tested under various process conditions on the pilot plant unit of our own design. The results of the experiments are shown and discussed. A required full-scale production capacity and the results of the experiments formed a base for a calculation of a membrane area for a full-scale unit and for an estimate of energy and investments for the reverse osmosis and the evaporator. A simplified calculation showed that the use of reverse osmosis is economically justified.