Microemulsions as reactors for silver sulfadiazine nanocrystal synthesis

The first goal of this work was the preparation of a water-in-oil microemulsion from components generally regarded as safe for use in humans. Stable formulations were prepared using isopropyl myristate (IPM), ethyl oleate (EO), and medium chain triglycerides (MCT) as the continuous phase. Dioctyl sodium sulfosuccinate (DOSS), and sorbitan monooleate (SMO) were used as surfactants. Tetraglycol (TG), and n-butanol were used as co-surfactants in some of the formulations. Ternary phase diagrams were prepared for the systems under study. DOSS-IPM solutions were found to form stable microemulsions over a wide composition range. Hence, IPM/DOSS/water systems were selected for further studies. The physico-chemical properties of the selected ternary system were then evaluated using electrical conductivity, rheology, dynamic light scattering, and sub-ambient differential scanning calorimetry. The results obtained from conductivity experiments are consistent with the formation of w/o microemulsions. All the IPM/DOSS/water systems exhibited Newtonian flow properties. The DLS results showed that the emulsified water droplets had an average diameter range of 6 to 16 nm, depending on composition. The microemulsions did not show droplet aggregation or coalescence over a one month period of observation as indicated by the multi-angle DLS study. Sub-ambient DSC investigations on the freezing of water in IPM/DOSS/water systems revealed three types of water in the system, non-freezable water, interphasal water, and free water.; The second goal of this work was the preparation of silver sulfadiazine nanoparticles. It was hypothesized that two separate microemulsions containing dispersed aqueous droplets of either sodium sulfadiazine or silver nitrate would react when mixed. The DLS results and ESEM images corroborate the successful formation of submicron silver sulfadiazine crystals. In the absence of any polymeric crystal growth modulators the particle size could not be maintained below 1 mum beyond 15 minutes after the mixing of the reagent microemulsions. In the presence of polyvinyl pyrrolidone (PVP) and polyallylamine hydrochloride (PAA) the AgSD crystals were maintained in the nanometer size range for up to 12 hours after preparation. These findings elucidate potential pathways for the stabilization of AgSD nanoparticles without the use of covalent capping agents which may be potentially toxic and inhibit pharmacologic activity.