Menthol, Borneol, Camphor and WS-3 Eutectic Mixture S

Advanced Materials Research Vol. 506 (2012) pp 355-358 © (2012) Trans Tech Publications, Switzerland doi:10.4028/www.scientific.net/AMR.506.355

Menthol, Borneol, Camphor and WS-3 Eutectic Mixture

S. Tuntarawongsa 1,a ,and T. Phaechamud 1,b ,*

1Department of Pharmaceutical Technology, Faculty of Pharmacy,

Silpakorn University, Nahkon Pathom, 73000 Thailand

[email protected], [email protected]

Keywords: Eutectic Mixture, menthol, borneol, camphor and WS-3

Abstract. 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.

Introduction Mixture of some solid materials is able to alter into the liquid like at room temperature that can be utilized as the solvent. Eutectic system is a mixture or solution which the ingredients solidify or liquefy simultaneously that unique composition of two (or more) components has the lower crystallization temperature or melting point [1] due to thermodynamic parameter change and total entropy increases [2]. For pharmaceutical field, eutectic system has been used in many proposes. Liquid solution obtained from eutectic mixture has been applied for some drugs to increase solubility, permeation and absorption [3-7] or used as oil phase in emulsion system [8,9]. The interesting application of liquid eutectic is to employ as deep eutectic solvent (DES) such as system consisting of quaternary ammonium salts and organic compound [10-13]. The advantages of this solvent system are less toxic, cheap, biodegradable and non flammable [10]. Typically, terpene compounds are used as eutectic components in many research works which menthol is the most of used. Menthol is the old traditional pharmaceutical active material for local anesthetic, pain reliever, antiflatulent and mild antimicrobial effect. Moreover, menthol is a permeation enhancer [14]. Menthol is also able to form the liquid eutectic with ibuprofen [3,5], lidocaine [7], CoQ 10 and essential oils [9]. In this study the simple liquid eutectic systems were prepared with menthol and other compounds and characterized their properties. The suitable liquid eutectic system will be selected for further application as liquid carrier for injectable dosage forms.

Experimental Materials Menthol (M), camphor (C), borneol (B) and N-Ethyl-5-methyl-2-(1-methylethyl)cyclohexane- carboxamide (WS-3;W) were purchased from P. C. Drug Center Co., Ltd., Bangkok, Thailand.

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Method Preparation of liquid eutectic system Six systems of liquid eutectic were prepared by physical mixing of menthol and camphor (M:C) or borneol (M:B) or WS-3 (M:W), camphor and borneol (C:B) or WS-3 (C:W), borneol and WS-3 (B:W) in various ratio (9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8 and 1:9). The physical appearance of them was evaluated which clear liquid mixtures obtained at room temperature were selected for next evaluations. Viscosity and rheology Viscosity and rheology at room temperature of each system were evaluated (n=3) using brookfield viscometer (DV-III Ultra programmable rheometer, Brookfield engineering laboratories, Inc., Middleboro, USA) performed in a cone-and-plate geometry with a cone no.40 or 50 for low viscosity and high viscosity, respectively. The shear rates ranged from 0.1 up to 100s -1. Surface tension Pendant drop technique was used for surface tension determination (n=3) using goniometer (FTA 1000, First Ten Angstroms, USA) Contact angle measurement Contact angle onto the glass plate of each system was measured by sessile drop technique (n=3) using goniometer (FTA 1000, First Ten Angstroms, USA) at 1 st second of contact time. Infrared spectroscopy The suitable liquid eutectic system was evaluated the interaction of the component by FT-IR spectrophotometer (Nicolet 4700, Thermo electron corporation, Madison, USA). The solid samples were evaluated using KBr disk method. The liquids samples were evaluated using the smart multi bounce HATR Combo kit set with zinc selenide avatar trough plate 45degree.

Results and discussion Liquid eutectic system The prepared mixtures that could transform from solid to clear liquid state at room temperature were the systems of M:C in the ratio of 8:2, 7:3, 6:4 and 5:5, M:B in the ratio of 8:2 and 7:3, M:WS-3 in the ratio of 6:4 and 5:5 but the mixture between C:B, C:W and B:W did not change to liquid like at room temperature. The mixture between menthol-camphor, menthol-borneol and menthol-WS-3 at other ratio did not alter to be the clear solution after mixing because only some ratio that melting point was lower than room temperature [15]. Evaluation of liquid eutectic system The system of M:W exhibited the highest viscosity following by M:B and M:C respectively as shown in Figure 1 and rheology of all liquid eutectic systems were Newtonian flow. Therefore molecular weight of component and ratio of the mixture influenced on the viscosity of liquid eutectic systems.

Fiqure 1. Viscosity of liquid eutectic systems at room temperature (n=3).

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Surface tension values of the selected systems are shown in Table 1. The surface tension of all system were around 28-29 mN/m that seem not to be affected from the type or ratio of the component. Contact angle were affected by viscosity. The highest viscosity was the highest contact angle was M:W system following with that of M:B and M:C, respectively as shown in Table 2 however all liquid eutectic systems were high wettable onto the glass plate.

Table 1 Surface tension of liquid eutectic systems (n=3). Surface tension (mN/m ± SD) Ratio M:C M:B M:W 8:2 28.76 + 0.20 28.23 + 0.27 - 7:3 28.98 + 0.11 28.16 + 0.56 - 6:4 28.94 + 0.17 - 28.10 + 0.07 5:5 28.69 + 0.54 - 28.04 + 0.53

Table 2 Contact angle of liquid eutectic systems (n=3). Contact angle (Degree ± SD) Ratio M:C M:B M:W 8:2 13.66 + 1.71 19.94 + 1.89 - 7:3 13.73 + 1.32 20.54 + 1.46 - 6:4 14.29 + 1.69 - 32.42 + 1.08 5:5 14.33 + 0.95 - 33.01 + 3.97

Form the above results, the suitable liquid eutectic was menthol and camphor system in ratio 5:5 due to its lowest viscosity. The high loading capacity for active compounds should be obtained for using this solvent without providing the too viscous environment of the prepared system. The IR spectra of menthol shown O-H stretching at 3,000-3,500 cm -1, C-O stretching at 1,000-1,200 cm -1 and C-H stretching at 2,800-3,000 cm -1(data not shown). For camphor, IR spectra shown C=O stretching group at 1,690-1,725 cm -1 and C-H stretching at 2,800-3,000 cm -1(data not shown). IR spectra of liquid eutectic consist of 5:5 menthol:camphor ratio shown all peaks that found in spectra of both menthol and camphor, therefore no chemical interaction of menthol and camphor was evident.

Conclusion The liquid eutectic system were obtained at room temperature from the systems of M:C in the ratio of 8:2, 7:3, 6:4 and 5:5, M:B in the ratio 8:2 and 7:3, menthol:WS-3 in the ratio 6:4 and 5:5. The rheology of all liquid eutectic systems were Newtonian flow. Surface tension did not affect by type and ratio of used component. Prepared eutectic systems were categorized as high wettable liquid onto the glass surface. The system which seemed to be an interesting solvent system was 5:5 menthol:camphor owing to it was lowest viscosity and IR spectra comfirm that there was no chemical interaction for this system.

Acknowledgements This research work was kindly supported by Faculty of Pharmacy, Silpakorn University and the National Nanotechnology Center, National Science and Technology Development Agency (Grant P-11- 00226).

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