Solubility of carbamazepine in aqueous solutions of sodium dodecyl sulfate

Abstract

Carbamazepine (CZ) is a hydrophobic antiepileptic drug with a very low water solubility. It is important to identify means of improving the solubility of such drugs for better formulation and absorption. One approach to increasing solubility of hydrophobic drugs is to solubilize them in surfactant micelles. Surfactants are compounds that form micelles above a certain critical micelle concentration (cmc). Hydrophobic drug are able to dissolve in the non-polar interior of these micelles and therefore achieve higher concentrations in solution. We have investigated the solubility of CZ in solutions of sodium dodecyl sulfate (SDS), an anionic surfactant frequently used in pharmaceutical systems. Concentrations of SDS below and above its cmc (8 mM) were used. Excess CZ was added to SDS solutions of varying concentrations, and the systems allowed to equilibrate at 26ºC for at least seven days. The mixtures were filtered, diluted appropriately with ethanol and analyzed spectrophotometrically at 286 nm using a Beckman DU7500 UV-visible diode array spectrophotometer. Our observations show that the aqueous solubility of CZ at 26ºC is 4.23 x 10-4 M. The solubility of CZ increases as a function of SDS concentration above the cmc. For example, CZ solubility is 4.4 times greater in 10mM SDS, 12.7 times greater in 20 mM SDS, and 59.8 times greater in 80mM SDS. Very little solubility enhancement is seen at SDS concentrations below the cmc. The results confirm that SDS micelles can solubilize CZ and significantly increase its total aqueous solubility.