Development and characterization of clove oil microemulsion

Pharmacia 70(1): 233–241 DOI 10.3897/pharmacia.70.e98096 Research Article Development and characterization of clove oil microemulsion Naelaz Zukhruf Wakhidatul Kiromah1, Nining Sugihartini2, Laela Hayu Nurani2 1 Pharmacy, Faculty of Health Sciences, Universitas Muhammadiyah Gombong, Yos Sudarso Street 461, Kebumen, Jawa Tengah, Indonesia 2 Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia Corresponding author: Nining Sugihartini () Received 28 November 2022 ♦ Accepted 27 January 2023 ♦ Published 22 March 2023 Citation: Kiromah NZW, Sugihartini N, Nurani LH (2023) Development and characterization of clove oil microemulsion. Pharmacia 70(1): 233–241. https://doi.org/10.3897/pharmacia.70.e98096 Abstract Clove oil is one type of essential oil from clove flower buds (Syzygium aromaticum) which contains eugenol compounds. Clove oil is volatile in nature and highly affected by heat, thus incorporating it in a microemulsion system can increase its shelf life of the oils. This study aimed to formulate and characterize microemulsion preparations with clove flower essential oil. The microemulsion existence region was determined by constructing a pseudo-ternary phase diagrams and prepared with four components, i.e. isopropyl myristate, tween-80 as a surfactant, polyethylene glycol 400 (PEG 400) as a co-surfactant, and water as the aqueous phase. The optimized clove oil microemulsion formulation was subjected to an evaluation of various parameters, such as organoleptic properties, %transmittance, pH, viscosity, stability, particle size, zeta potential, and polydispersity index (IP). Based on the results of the study, the highest compound component in clove oil was eugenol with a % area of 63.79%. The results revealed that the construction of a phase diagram and the use of the phase titration method constituted a suitable technique for the preparation of microemulsions as most of the formulations were transparent. It was found that the tween-80:PEG 400 ratio of 2:1 with an oil:S-mix ratio of 1:9 generated an optimum results. The clove oil microemulsion had a globule size of 17.69±0.025nm, a polydispersity index value of 0.057±0.0043, zeta potential of-5.36±0.23mV, and a pH value of 7.3±0.1, a viscosity value of 466.7±9.06., and %transmittance of 99.9±0.1. According to these findings, the microemulsion formulation might serve as a suitable drug delivery system. Keywords microemulsion, clove oil, formulation, characterization Introduction The clove (Syzygium aromaticum) is included in the Myrtaceae family, which is widely produced in Indonesia. The Clove is primarily produced in Indonesia, accounting for roughly 70% of total global clove production yearly (Amelia et al. 2017). Clove plants are also used to obtain, among other things, clove oil, a type of essential oil, from clove flower buds (Syzygium aromaticum), which contains eugenol compounds. Clove oil has antibacterial properties and is commonly used to treat many disorders, such as toothache, GI disturbances, respiratory diseases, and inflammation (Cui et al. 2015). It shows anti-ulcer and gastroprotective activity in rat models with indomethacin and ethanol-induced ulcers (Tanzeem et al. 2019). The essential oil content in clove flowers reaches 21.3%, with a eugenol content of 78–95% (Hadi 2013). The potency of clove leaf essential oil still needs to be improved. It is immiscible with water, which minimizes contact with polar ingredients (Van de Vel et al. 2019). Copyright Kiromah NZW et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 234 Kiromah NZW et al.: Formulation and characterization of clove oils microemulsion Clove essential oil has also been widely used in the food and perfume industries, but it has weaknesses like being a very volatile compound, unstable to heat, light, and air (Cui et al. 2015). Hence, to improve clove essential oil’s stability, solubility, and effectiveness, it may be prepared in microemulsions (Saini et al. 2019). Microemulsions are thermodynamically stable, transparent, and homogeneous (Sharma et al. 2016). They can increase drug solubility, have a long shelf life, be easily prepared, and increase the bioavailability of poorly soluble drugs (Hasrawati et al. 2016). They can also be used as a drug delivery system by multiple; routes and makes microemulsions is an promising dermal delivery route through an efficient drug delivery route (Muzaffar et al. 2013). Microemulsions may be used for enhanced oil recovery and for formulations for drugs, food, and cosmetics that are edible using oral or transdermal administration methods as delivery methods vehicles for dosages to be released under control (Callender et al. 2017). A microemulsion is a bicontinuous system containing water and oil, separated by a surfactant and a cosurfactant. Microemulsions have low interfacial tension. It will be challenging to achieve the required interface area if only a single surfactant is used; thus, a co-surfactabt is needed (Deepak and Vedha Hari 2013). The surfactants often used in microemulsion preparations are non-ionic surfactants, such as tween-80 (Hidayat et al. 2020). The co-surfactants are usually short- to medium-chain alcohols (C3–C8), such as PEG 400. Polyethylene glycol (PEG) is a polymer with different molecular weights that exhibits excellent properties, such as biocompatibility, minimal toxicity, and good solubility (Fan et al. 2020). The combination of the surfactant tween-80 and the co-surfactant PEG 400 in microemulsion has been employed in previous studies with the use of various oils, such as oleic acid oil (Sisak et al. 2017), citronella oil (Hasrawati et al. 2016), and limonene (Ramli et al. 2019). This study aimed to make a microemulsion preparation containing clove flower essential oil with various concentrations of tween 80 as a surfactant and PEG 400 as a co-surfactant. The results of the formulation of the microemulsion preparation will be characterized to obtain a stable and high-quality clove flower essential oil microemulsion. Materials and methods Materials The main ingredients used in this research was clove flower essential oil, which was obtained from the Center of Essential Oil Studies (CEOS) of the Indonesian Islamic University, Yogyakarta. The additives used in the formulation of microemulsion gel preparations, including isopropyl myristate, tween-80, PEG 400, and aquadest, were of pharmaceutical grade and obtained from CV Nurul Jaya Medicallabsains, Banyumas. Instruments in this study were: Iwaki Pyrex glassware, GC-MS instrument, magnetic stirrer, digital pH meter (Pico+ Labindia, Mumbai, India), V-Visible spec- trophotometer (UV, 1700, Shimadzu, Japan), Brookfield viscometer (DV- II+Pro Brookfield, USA), and Zetasizer (Malvern instrument ltd ZE (...truncated)