Preparation and evaluation of a titrated extract of Centella asiatica injection in the form of an extemporaneous micellar solution

The micellar solution of titrated extract of Centella asiatica (TECA) was formulated by solubilizing TECA into a mixture of propylene glycol and ethoxylated hydrogenated castor oil. An extemporaneous TECA micelle was then successfully prepared by diluting this original micellar formulation with water, saline or isotonic glucose solution. A mixture of propylene glycol and ethoxylated hydrogenated castor oil achieved an acceptable solubilization of TECA up to 180 mg/ml via a formulation of micelle. The drug content of the original micellar formulation stored at 55 degrees C over 60 days was almost constant. The extemporaneous TECA micelle prepared by diluting the original micellar formulation was physically stable for up to 23 h with shaking and 55 h without shaking depending on dilution ratio and medium. The estimated distribution of mean particle size was between 15.9 and 32.6 nm. The osmotic pressure and erythrocytic hemolysis were measured for the formulation with various media. The osmotic pressure of the formulation was found to be much lower than that in a commercially formulated propylene glycol-based injection. The erythrocytic hemolysis by the micellar solution was much more reduced compared with that by the propylene glycol-based preparation. Pain score after the peritoneal injection of the micellar solution was assessed by counting the number of writhe in ICR mice and compared with that in the conventional injection. The injection of extemporaneous TECA micellar solution did not show any single writhe in mice as like as saline. This indicates that pain is reduced dramatically. These results indicated that a micellar solubilization, followed by an extemporaneous dilution, might be a choice of formulation for TECA injection with reducing the pain arising from the intramuscular injection. (C) 1997 Elsevier Science B.V.