Sarun Tuntarawongsa

Menthol, Borneol, Camphor and WS-3 Eutectic Mixture

Eutectic system is a mixture or solution which the ingredients solidify or liquefy simultaneously. A eutectic mixture is therefore that unique composition of two (or more) components that has the lower crystallization temperature or melting point. This aim of this study was to prepare and characterize the eutectic systems containing menthol, borneol, camphor and N-Ethyl-5-methyl-2-(1-methylethyl) cyclohexanecarboxamide (WS-3). Menthol is able to form liquid eutectic at room temperature with camphor in the ratio of 8:2, 7:3, 6:4 and 5:5 whereas menthol and borneol in the ratio of 8:2 and 7:3, menthol and WS-3 in the ratio of 6:4 and 1:1. The rheology behavior of all liquid eutectic systems was Newtonian flow which the surface tension was in the range of 28-29 mN/m. From contact angle measurement, all liquid eutectic systems were categorized as high wettability to the glass plate. The suitable liquid eutectic system for further application as liquid carrier for injectable active compounds was 1:1 menthol:camphor because of its lowest viscosity. IR spectra indicated that there was no chemical interaction of these two materials in the selected liquid eutectic mixture.

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

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.

Polymeric Eutectic System

The liquid eutectic system comprising 1:1 menthol:camphor was selected to use as solvent due to it was lowest viscosity. Both menthol and camphor used in this eutectic system have been reported for their many pharmaceutical used. Various polymers were tested for their solubility in this eutectic system. Eudragit® EPO showed the highest solubility. Eudragit® EPO was the one of biocompatible polymer which could dissolve in this eutectic system up to 40% w/w with no chemical interaction of each compound. Viscosity of this system showed the exponential curve as a function of polymer concentration but all concentration showed the newtonian rheology. The pH and surface tension were slightly affected by type and amount of polymers. The obtained polymeric eutectic mixture should control the drug release for pharmaceutical applications.

Peppermint oil/doxycycline hyclate-loaded Eudragit RS in situ forming gel for periodontitis treatment

Antibiotic-loaded in situ forming gels are particularly attractive for periodontitis treatment. They are in a sol form and gradually alter to a solid-like depot after administration into a periodontal pocket to deliver and maintain the effective high level of drug in the gingival crevicular fluid. Solvent-inducing in situ forming gel mostly exhibits the burst drug release owing to rapid diffusion of solvent. This study incorporated peppermint oil to modulate the drug release and the gel characteristics of doxycycline hyclate-loaded Eudragit RS in situ forming gel systems. Peppermint oil increased the viscosity and syringeability of the Eudragit RS solution comprising NMP as solvent and retarded the water penetration. Therefore the diminishment of burst liberation and the prolongation of drug release with an addition of peppermint oil were attained with concentration dependence mainly following Fickian diffusion mechanism. The drug release from the membrane-less diffusion method was apparently slower than that from the dialysis method because the rapid phase separation into solid-like matrix through a direct contact with dissolution medium generated a hard surrounding shell. These solvent exchange-inducing in situ forming gels comprising peppermint oil effectively inhibited Staphylococcus aureus, Escherichia coli, Streptococcus mutans and Porphyrommonas gingivalis; therefore, they exhibited the potential use as localized delivery systems for periodontitis treatment.Graphical Abstract

Homogenization and Melt-Emulsification Techniques for Ibuprofen Particle Size Reduction: Effect of Tween 80 & Sonication

Ibuprofen suspensions were prepared by simple homogenization with melt-emulsification process. Tween 80 was used as stabilizer. The homogenized suspensions were evaluated and compared with melt emulsificated suspension. The pH value and rheology behavior were not difference. The viscosity was very low. Zeta potential was -10 to -25 mV. In this study, the suitable process to minimize particle size of ibuprofen suspension was melt emulsification follow by sonication. This process could be developed to obtain nanosuspension by adjust sonication process and improved formulation to obtain suitable nanosuspension.

Capsaicin Injectable In-Situ Forming Gels

Capsaicin exhibits the analgesic and anti-inflammatory activities, therefore it is interesting to apply this natural active compound for periodontitis treatment by local drug delivery system such as intra-canal route. Capsaicin in-situ forming gels were prepared in this research work. The viscosity, gel forming property and capsaicin release were evaluated. 30%W/W eudragit RS 30D in N-methylpyrrolidone (NMP) employed as gel base was physicaly stable after sterilization with autoclaving and exhibited the in-situ forming gel property. This gel base was still clear when capsaicin was less than 0.0094 %w/w. When the system contacted with phosphate buffer pH 6.8 the turbid gel was appeared rapidly at the interface. Viscosity of system depended on the amount of eudragit RS 30D. The rheology of systems was newtonian flow and amount of capsaicin tincture did not affect the rheological behavior. The release rate and amount of capsaicin release form gels were lower than those of capsaicin solution. The sustainable release of capsaicin could be obtained from the developed in-situ forming gel.