Transformation of eutectic emulsion to nanosuspension fabricating with solvent evaporation and ultrasonication technique

Thawatchai Phaechamud,1 Sarun Tuntarawongsa2 1Department of Pharmaceutical Technology, 2Pharmaceutical Intelligence Unit Prachote Plengwittaya, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand Abstract: Eutectic solvent can solubilize high amount of some therapeutic compounds. Volatile eutectic solvent is interesting to be used as solvent in the preparation of nanosuspension with emulsion solvent evaporation technique. The mechanism of transformation from the eutectic emulsion to nanosuspension was investigated in this study. The 30% w/w ibuprofen eutectic solution was used as the internal phase, and the external phase is composed of Tween 80 as emulsifier. Ibuprofen nanosuspension was prepared by eutectic emulsion solvent evaporating method followed with ultrasonication. During evaporation process, the ibuprofen concentration in emulsion droplets was increased leading to a drug supersaturation but did not immediately recrystallize because of low glass transition temperature (Tg) of ibuprofen. The contact angle of the internal phase on ibuprofen was apparently lower than that of the external phase at all times of evaporation, indicating that the ibuprofen crystals were preferentially wetted by the internal phase than the external phase. From calculated dewetting value ibuprofen crystallization occurred in the droplet. Crystallization of the drug was initiated with external mechanical force, and the particle size of the drug was larger due to Ostwald ripening. Cavitation force from ultrasonication minimized the ibuprofen crystals to the nanoscale. Particle size and zeta potential of formulated ibuprofen nanosuspension were 330.87±51.49 nm and -31.1±1.6 mV, respectively, and exhibited a fast dissolution. Therefore, the combination of eutectic emulsion solvent evaporation method with ultrasonication was favorable for fabricating an ibuprofen nanosuspension, and the transformation mechanism was attained successfully. Keywords: eutectic, emulsion solvent evaporation, ibuprofen, nanosuspension, ultrasonicatio

Properties and thermal behavior of natural deep eutectic solvents

Natural deep eutectic solvents (NADES) have shown to be promising sustainable media for a wide range of applications. Nonetheless, very limited data is available on the properties of these solvents. A more comprehensive body of data on NADES is required for a deeper understanding of these solvents at molecular level, which will undoubtedly foster the development of new applications. NADES based on choline chloride, organic acids, amino acids and sugars were prepared, and their density, thermal behavior, conductivity and polarity were assessed, for different NADES compositions. The NADES studied can be stable up to 170 Â°C, depending on their composition. The thermal characterization revealed that all the NADES are glass formers and some, after water removal, exhibit crystallinity. The morphological characterization of the crystallizable materials was performed using polarized optical microscopy which also provided evidence of homogeneity/phase separation. The conductivity of the NADES was also assessed from 0 to 40 Â°C. The more polar, organic acid-based NADES presented the highest conductivities. The conductivity dependence on temperature was well described by the Vogelâ Fulcherâ Tammann equation for some of the NADES studied.Fundação para a Ciência e a Tecnologia (FCT/MEC) through the grants PTDC/EQUEPR/12191/2010/ENIGMA, SFRH/BD/47088/2008 and SFRH / BPD / 44946 / 2008. We further acknowledge the financial support of FCT/MEC through the project ENIGMA — PTDC/EQU-EPR/121491/2010, and the project PEst-C/ EQB/LA0006/2013 and FCOMP-01-0124-FEDER-020646.We also acknowledge the funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. REGPOT-CT2012-316331-POLARIS, and from the Project “Novel smart and biomimetic materials for innovative regenerative medicine approaches (Ref.: RL1 — ABMR — NORTE-01-0124-FEDER- 000016)” co-financed by the North Portugal Regional Operational Programme (ON.2 — O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)