Development of a novel dosage form for intramuscular injection of titratedextract of Centella asiatica in a mixed micellar system

Titrated extract of Centella asiatica (TECA), a drug used in treating syste mic scleroderma, is poorly water-soluble. A conventional dosage form for th e intramuscular injection of TECA, propylene glycol (PG)-based TECA solutio n, causes severe pain after intramuscular injection. To improve the solubil ity of TECA and reduce pain after injection, mixed micellar systems compose d of 10%, surfactant mixture (Tween 20 and Tween 85) and 90%, phosphate-buf fered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micell ar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). T he droplet size of micelles gradually decreased with the increasing ratio o f Tween 20 to Tween 85 from 0:10 to 4.6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared wit h Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize T ECA more than 10 mg/ml and the resultant droplet sizes were less than 2 mum . No significant changes were observed in the droplet sizes and asiaticosid e contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remar kably lower than those of PG-based TECA solution and similar to that of sal ine solution, irrespective of dilution ratios. Most importantly, they marke dly reduced the number of writhes compared with PG-based TECA solution afte r injection to mice. All of these results suggest that these three TECA mic ellar formulations prepared with Tween 20 and Tween 85 improved the solubil ity of TECA and reduced pain following injection, possibly due to the decre ase in osmotic pressure. Thus, these micellar formulations composed of opti mum ratios of Tween 20 and Tween 85 may have a potential as dosage forms fo r the intramuscular injection of a poorly water-soluble TECA. (C) 2001 Else vier Science B.V. All rights reserved.