Taste masking of enalapril maleate by microencapsulation in Eudragit EPO® microparticles.

Microencapsulation is one of the most commonly used taste masking techniques. It can be accomplished by various methods, including coacervation, solvent evaporation, extrusion and spray-drying. Enalapril maleate, a bitter-tasting ACE-inhibitor, is available worldwide in conventional tablet formulations and as oral solution in the USA. The purpose of this study was to develop enalapril-loaded microparticles using spray-drying and to test their taste masking potential. Eudragit EPO® was used as a taste masking polymer for the preparation of a drugpolymer suspension. The suspension was then spray-dried under the following conditions: inlet temperature 65 °C, outlet temperature 30 °C, aspiration 100% and pump rate 10%. The drug-to-polymer ratio was varied and seven different microparticle models were developed. The yield of spray-dried particles ranged from of 51.3 to 85.4%, drug loading varied from 7.75 to 24.69% and encapsulation efficiency ranged from 58.5 to 95.7%. The particle size varied between 5.00 µm and 17.47 µm and the moisture content varied between 7.1% and 10.3%. In vitro taste assessment revealed minimal or no ENA release in artificial saliva. In vivo studies (with experimental animals and healthy volunteers) were used to evaluate the taste masking potential of spray-dried microparticles of enalapril maleate and Eudragit EPO®.

Erufosine: a membrane targeting antineoplastic agent with signal transduction modulating effects.

The ether lipid analog erufosine (erucylphospho-N,N,N,-trimethylpropylammonium, ErPC3) has high activity against leukemic cells without affecting the normal hematopoiesis. It belongs to the group of alkylphosphocholines (APC) that are inhibitors of protein kinase C and phospholipase C. However, the mechanism of action of erufosine remains rather unclear. We focused on combination effects with the tyrosine kinase inhibitor imatinib mesylate (gleevec, former STI-571 or CGP-57148) against two chronic myeloid leukemia (CML)-derived cell lines (K-562 and BV-173). The influence of erufosine on proteins involved in the phosphatidylinositol-3-phosphate pathway and on expression of the retinoblastoma protein Rb was studied, the latter being a key component for cell cycle entry and progression in mammalian cells. The consecutive treatment of K-562 and BV-173 cells with erufosine (2.5, 5, 15, 30 microM) and imatinib mesylate (0.05, 0.1 microM) led to synergism as measured by the MTT-dye reduction assay and this is reason to hypothesize that such combinations could be beneficial for relapsed patients with drug-resistant disease. Whole cell lysates from K-562 and BV-173 were investigated for the expression of Rb, PKB/Akt, pAkt, and p27 by Western blot. Erufosine caused decreases of pAkt and CML fusion protein p210 (BCR-ABL) protein expression, but induced the Rb protein expression in K-562 cells. A parallel increase in p27 level was observed after 24 and 48 h treatment. These alterations in signal transduction could be an explanation for the drug interaction found. Furthermore, Rb is a substrate of caspases and is cleaved during apoptosis as already evidenced for BV-173 cells. Our experimental findings suggest that erufosine acts through induction of changes in protein signaling and especially through Rb induction. This unique mode of action makes it an attractive partner for combination therapies, for example, in combination with imatinib mesylate for treatment of CML.