In this study, indomethacin-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed in liquid, solid and carrier-mediated formulations in order to improve the solubility of this model poorly water soluble drug. Liquid SNEDDS based on Capryol™ 90 (oil phase), Cremophor® RH 40 (surfactant) and Transcutol® HP (co-surfactant) were thermodynamically stable and produced clear nanoemulsions upon dilution. Optimized liquid formulations were transformed into solid SNEDDS by adsorption onto the inert carriers Syloid® XDP 3150, Neusilin® US2 and Florite® PS-200. Ratios of adsorbent: liquid SNEDDS of 1:1.5 and 1:2 resulted in solid SNEDDS formulations that exhibited fair to passable powder flow properties. Carrier-based solid SNEDDS formulations were developed using the solid self-emulsifying carriers Gelucire® 44/14 and Gelucire® 48/16 and prepared by hot melt extrusion. The absorbent-based solid SNEDDS maintained the self-nanoemulsification properties of the original liquid SNEDDS formulations, with solid state analysis suggesting that the drug had remained in a dissolved state within these formulations. Similarly, physical characterization of the carrier-based solid SNEDDS formulations indicated that the drug was molecularly dispersed within the system and that the self-nanoemulsifying properties of the carrier were unchanged. The only exception was those formulations prepared at the highest drug: carrier ratio (3: 10). For both absorbent-based and carrier-based solid SNEDDS, the in vitro dissolution efficiency was significantly higher than that obtained for the pure drug. However, incorporation of adsorbents into Gelucire®-based solid SNEDDS formulations resulted in reduced dissolution of the drug. Gelucire®48/16-based solid SNEDDS prepared at 50oC were more physically stable to storage at 30oC/75% RH for 6 months than formulations processed at 40oC, suggesting that complete melting of the carrier during manufacture is essential for production of physically stable formulations. Overall, a range of liquid, solid and carrier-based SNEDDS formulations were successfully developed and offer useful alternatives to improving the solubility of poorly water-soluble drugs
