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J. Cosmet. Sci., 74.6, 348–359 (November/December 2023)
*Address all correspondence to Ashlesha P. Pandit, ashlesha.pandit@gmail.com
Microemulgel-Based Delivery of Ketoconazole Using Tea
Tree Oil for Treatment of Dandruff
ANUPAMA KESBHAT, SUMEET S. DHAKANE, PRATIKSHA LABADE, PALAKSHI LAD
AND ASHLESHA P. PANDIT
Department of Pharmaceutics, JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathawade,
Pune, Maharashtra, India (A.K., S.D., Pr.L., A.P.)
Bharati Vidyapeeth (DTU) Medical College, Pune, Maharashtra, India (Pa.L.)
Accepted for publication November 01, 2023.
Synopsis
Microemulsion can potentially deliver skin care actives. A microemulsion vehicle composed of several skin-
beneficial oils can also provide extra skin care efficacy in addition to skin care actives. Therefore, the current
study was intended to utilize a combination of skin-beneficial oils, such as tea tree oil (TTO)-coconut oil,
during the formulation of microemulsion. Microemulsion was formulated using pseudo-ternary phase
diagram, wherein oil mixtures at various surfactant/cosurfactant ratios were used. Microemulsion area of this
ternary plot was also selected to get ketoconazole-loaded microemulsion. Microemulsion was characterized
to achieve particle size of 326.3 nm, zeta potential of +75.6 mV, and polydispersity index (PDI) of 0.5129.
Thus, stable microemulsion was further converted to microemulgel for easy application on the scalp with a
good viscosity (3,400 cp). Scanning electron microscopy (SEM) images clearly depicted the micro-droplets
dispersed in the continuous phase. Additionally, antifungal activity of ketoconazole loaded microemulgel
(38 mm) and simple microemulsion (without ketoconazole, 12 mm) against Malassezia furfur revealed a large
zone of inhibition. This confirmed the combined effect of microemulsion and the use of TTO. Ketoconazole-
loaded microemulgel shows great promise as an advanced topical drug delivery system for treating topical
fungal infections.
INTRODUCTION
Dandruff is the chronic scalp infection characterized by itching and flaking of skin on the
scalp and the hairy parts of the skin.1 It is a common disorder mostly found in the 18–25
age group and at puberty, and affects 5% of the global population. It becomes infrequent
after the age of 50.2 While it is not serious or contagious, it is difficult to treat and can cause
loss of confidence among patients. Dandruff is also known as seborrheic dermatitis, mainly
caused by the fungi Malassezia furfur (also known as Pityrosporum ovale) and is a species of
yeast that is naturally found on the skin surface of humans and some other mammals.3,4
Today, advanced delivery technologies such as microemulsion, nano-emulsion, nanoparticles,
and liposome are often used instead of conventional technologies for effective delivery

349 Treatment of Dandruff
of the active ingredients to the target site (mostly the epidermis).5 One such delivery is
microemulsion. Microemulsion is transparent and thermodynamically stable system with
a high drug loading capacity, low viscosity, and micron-range globule size that contributes
to its long-lasting effect—thus serving as an alternative approach.6 Microemulsion is a
potential way to deliver skin care actives.7
Previous research work was focused on the development of advanced topical drug delivery
systems like microemulsion and nano-emulsion as carriers for transdermal delivery of
antifungal drug, ketoconazole loaded hydrogel for effective topical delivery against fungal
infections, and resveratrol-loaded microemulsion based formulations using more than
one skin-beneficial oil.7-9Additionally, another study was aimed to develop a formulation
containing plant extracts or essential oils to prevent dandruff.10
Azoles are also commonly used to treat antifungal infections like dandruff. In this study,
ketoconazole (an imidazole) was selected as antifungal agent belonging to BCS class
II, which had low solubility and high permeability. Azoles and allylamines inhibit the
synthesis of fungal ergosterol that leads to cause defects in the fungal cell wall, thus serving
as a fungistatic agent.11 Tea tree oil (TTO), also known as melaleuca oil, is an essential oil
that is obtained from steaming the leaves of Australian tea tree plant.12 The addition of
TTO in the formulation provided a synergistic antifungal effect.12,13
In brief, the current study was focused on the application of both TTO and coconut oil by
forming microemulsion with an aim to get better availability and diffusion of ketoconazole
at the site of application. Furthermore, microemulsion was converted to microemulgel to
retain and cover a wide area at the scalp to treat dandruff. In this study, the microemulsion
region was located at the ternary phase diagram. Next, microemulsions were characterized
by measuring particle size, polydispersity index (PDI), zeta potential, and antifungal study
against the dandruff causative micro-organism M. furfur.
MATERIALS AND METHODS
MATERIALS
Ketoconazole was generously gifted by Aarti Drugs Ltd., India. TTO was procured from
Kanth Saanvi Essentials, Delhi, India.
METHODS
Solubility of ketoconazole in oil, surfactant, and cosurfactant. The solubility of ketoconazole in
various oils (TTO, coconut oil), surfactant (Tween 80) and cosurfactant propylene glycol was
determined by dissolving an excess amount of drug. The mixtures were then continuously
stirred in an orbital shaker (Bio Technics India, Maharashtra, India) for 48 hours, followed by
centrifugation in a high-speed centrifuge at 5,000 rpm (REMI Lab World, Maharashtra, India)
for 15 minutes. Supernatant was then collected and diluted with n-hexane, filtered through a
0.45 µm membrane filter and analyzed using a double beam UV-1800 visible spectrophotometer
(Shimadzu Corporation, Kyoto, Japan) at 244 nm.1 The solubility of ketoconazole in oil plays
a vital role in making it available in solubilized form when used in microemulsion.7 Therefore,
the solubility study of drug in oil, surfactant, and cosurfactant was an important criteria for the
screening and selection of components to formulate further as microemulsion.