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ABSTRACT
The objective of present study was to develop sorbitan monostearate (span 20) and sunflower oil (SO) based
organogels for topical drug delivery. The organogels were prepared by dissolving sorbitan monostearate in
sunflower oil (60°C). Terbinafine HCl was used as a model antifungal drug. The formulated organogels were
evaluated for their appearance, pH, viscosity, gel to sol transition study, drug content, in-vitro diffusion study,
antifungal activity and stability studies. The pH range of the organogels was simulated to the skin pH
conditions and the gel-sol transition study indicated that as the concentration of the gelator was increased,
there was a subsequent increase in the transition temperature. As the concentration of Span 60 increased, there
was a proportionate decrease in drug release pattern and the drug release profile of all the formulations were
followed zero order kinetic model and the mechanism of drug release were found to be non-fickian diffusion
controlled. All the formulations were able to restrict the growth of Candida albicans efficiently as comparable
to the marketed product. Based on the results, the developed organogels can be used as an efficient drug
carrier for the topical delivery of Terbinafine HCl.
Keywords: Terbinafine HCL, Sunflower oil, Span-60, Organogels.
INTRODUCTION
Fungal infections of skin are one of the common formulating them in an advantageous way [2].
dermatological problems. It has been estimated that In a recent development, organogels have been
about 40 million people have suffered from fungal shown to provide a very promising topical drug
infections in developing and under developed delivery vehicle. Organogel, a viscoelastic system,
nations. The progression of fungal infections can be can be regarded as a semi-solid preparation which
rapid and serious due to compromising with immune has an immobilized external a polar phase. The polar
function. Dermatophytes are one of the most phase gets immobilized within spaces of the three-
frequent causes of tinea and onchomycosis. dimensional networked structure formed due to the
Candidal infections are also among the most physical interactions amongst the self assembled
widespread superficial cutaneous fungal infections. structures of compounds regarded as gelators. In
Even, candida can invade deeper tissues as well as general, organogels are thermodynamically stable in
the blood which leads to life threating systemic nature and have been explored as matrices for the
candidiasis, when the immune system is weakened. delivery of bioactive agents [3].
[1] A wide variety of vehicles ranging from solid to Organogels have been investigated successfully as
semisolids and liquid preparations are available for dermal pharmaceutical formulations. The
topical treatment of dermatological diseases. Topical formulations designed for topical applications
drug administration is a localized drug delivery should be able to interact with the skin, which acts
system anywhere in the body through ophthalmic, as an anatomical and biological barrier for drug
rectal, vaginal and skin as topical route. However, penetration to the systemic circulation. Many
the major barrier of the skin is the stratum corneum, organic substances, like lipids, work as a penetration
the top layer of the epidermis. Low molecular enhancer. The cosmetics industry employs
weight (≤500 Da), lipophilicity, and effectiveness at organogels in personal care products like sunscreens,
a low dosage are the ideal characteristics of the lipsticks, and moisturizers. The food industry
drugs for transdermal delivery. Thus, the therapeutic utilizes organogel-based products for structuring
effectiveness of the existing drugs is improved by edible oils at low concentrations of the gelator
Address for correspondence: molecules. The commonly used organo gelators
Dr. Shankrayya.M include monoacylglycerols, diacylglycerols,
P.G. Dept. of Pharmaceutics, triacylglycerols, fatty acids, fatty alcohols, waxes,
S.C.S College of Pharmacy, wax esters and sorbitan monostearate.
Harpanahalli-583131. Karnataka. India. Sorbitan monostearate is a non-ionic surfactant
E-mail:guruscs1008@rediffmail.com which is hydrophobic in nature and forms organogel
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Shankrayya et al,: Terbinafine hydrochloride organogels for topical delivery
of organic solvents (e.g., hexadecane, isopropyl shown in Table 1. The hot mixture when cooled to
myristate, and a range of vegetable oils like sesame room temperature forms organogel at the sorbitan
oil, groundnut oil, olive oil, soybean oil, sunflower monostearate concentration ≥CGC. The
oil). Sorbitan monostearate based organogels have formulations which did not show flow on inversion
also been developed for pharmaceutical applications were selected as the representative samples for
[4] . further characterization. Terbinafine hydrochloride
Sunflower oil is the non-volatile oil compressed was added to the organogels as a model antifungal
from the seeds of sunflower (Helianthus annuus). drug at a concentration of 1% w/w.[4]
Sunflower oil is commonly used in food as frying Table-1: Composition of Organogel Formulations
oil, and in cosmetic formulations as an emollient [5]. Formulation Span60 Sunflower oil
Terbinafine HCl is most commonly prescribed Code (%) (%)
antifungal drug. Terbinafine HCl is emerging as the F1 1.5 8.5
good treatment option for virtually all forms of F2 2.0 8.0
susceptible Candida infections in both immune F3 2.5 7.5
competent and immune compromised hosts. It acts F4 3.0 7.0
by blocking the synthesis of ergosterol, an essential F5 3.5 6.5
component of the fungal cell membrane. Clinical EVALUATION STUDIES
efficacy of topical antifungal therapy depends on the Drug-polymer compatibility studies:
drug ability to penetrate into the SC and the duration Compatibility studies of pure drug, Span 60 and the
of treatment. Hence, organogel formulations mixture of both drug and Span 60 were carried out
appeared to be a viable approach for topical delivery using Fourier Transform Infrared Spectrophotometer
of terbinafine HCl. The solubilisation of terbinafine (Shimadzu FT-IR 8400-S ) in the range of 400-
HCl in organogel would improve its topical 4000cm-1 by KBr disc method.[7]
availability [6]. Physical appearance:
Keeping these facts into consideration, the current The prepared organogels formulations were
study reports the development of organogels using observed for their colour, homogenecity,
sorbitan monostearate as the organo gelator and consistency, appearance and texture.[8]
sunflower oil as the organic phase. The presence of pH determination:
sunflower oil may impart its beneficial effects when The pH was measured for each organogel using a pH
the organogel is applied topically to provide more meter (Hanna-213, Portugal) by direct immersion of
sustained topical antifungal effect of Terbinafine the electrode.[8]
HCl. Determination of viscosity:
MATERIALS AND METHODS: The viscosity of prepared organogels was
Materials: determined using a Brook field viscometer. The
Terbinafine hydrochloride was purchased from sample holder taken for the viscosity measurement
Yarrow. Chem. Product. Ltd. Mumbai, Sorbitan was filled with the sample and then inserted into the
monostearate (Span 60) from SD Fine chem. Ltd. flow jacket mounted on the viscometer. The sample
Mumbai, Sunflower Oil from Kaleesuwari. Refinery. adapter (spindle LV 64) rotated at optimum speed to
Pvt. Ltd and all other chemicals used were of measure the viscosity of the preparation.[9]
analytical grade. Gel-Sol Transition study:
Preparation of organogels: Organogels were incubated at various temperatures
The required quantity of sorbitan monostearate was in the range of 30°C and 60°C in a constant
dissolved in sunflower oil (60°C, 500 RPM). The temperature water bath. An increment of 5°C was
stirring was continued for 15 min under similar made after 5 min incubation at previous temperature.
experimental condition to obtain a homogenous Samples were analyzed by inverted test tube method
transparent mixture. The optimization of the after each incubation period. The temperature at
composition of the organogel was done by varying which samples started flowing was recorded as gel-
the concentration of sorbitan monostearate from sol transition temperature (Tg).[10]
1.5% w/w to 3.5% w/w. The minimum gelator Drug Content:
(SMS) concentration required for inducing gelation Drug content was determined using a UV
is called the critical gelator concentration (CGC). Spectrophotometric method by measuring the
The compositions tested for the gel formation are absorbance at 282 nm. 10mg of gel was dissolved in
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Shankrayya et al,: Terbinafine hydrochloride organogels for topical delivery
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Shankrayya et al,: Terbinafine hydrochloride organogels for topical delivery
150
F1
0
0 5 10 15
Time(mins)
The release behaviors of the drug from the thoroughly by investigating various properties. The
organogels were subjected using various release organogels were stable, smooth and the mechanical
kinetic models. The release of the drug followed properties (viscosity) increased with the increase in
zero-order release kinetics in all the organogels. The the organogelator (sorbitan monostearate)
type of drug diffusion from the organogels was concentration. The Terbinafine hydrochloride loaded
estimated by fitting the released data in the organogels showed diffusion-mediated release of
Korsmeyer–Peppas model. The diffusion coefficient drug from the organogel matrix. The antifungal
(n value) of the organogels varied from 0.61 to 0.78, activity showed a good inhibitory action of the drug-
which suggested a non-Fickian release behavior. loaded organogels against Candida albicans .
The optimized organogel (F5) formulation showed Hence, the developed organogels can be considered
antifungal activity when tested microbiologically by as probable matrices for a controlled release of the
cup plate technique. The values of the zone of antimicrobials for topical application.
inhibition produced by optimized organogel (F5) ACKNOWLEDGEMENTS
and marketed cream were shown in the table 3. It is The authors are highly indebted to President,
obviously clear that anti-fungal activity optimized Secretary, TMAE Society, and Principal, S. C. S.
organogel (F5) is higher than the marketed cream. College of Pharmacy, Harapanahalli, Karnataka,
Stability studies indicated that the optimized India for providing necessary facilities to carry out
formulation was stable at room temperature with no the study.
appreciable change in surface characteristics,
viscosity, pH and drug content. REFERENCES
CONCLUSION [1] Sevgi Gungor, M Sedef Erdal , Buket Aksu.
Sorbitan monostearate and sunflower oil-based New Formulation Strategies in Topical
organogels were prepared and characterized Antifungal Therapy. Journal of Cosmetics,
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Shankrayya et al,: Terbinafine hydrochloride organogels for topical delivery
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