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American Journal of Food Science and Health
Vol. 2, No. 5, 2016, pp. 123-128
http://www.aiscience.org/journal/ajfsh
ISSN: 2381-7216 (Print); ISSN: 2381-7224 (Online)
* Corresponding author
E-mail address: [email protected] (Ravi T. P. U.)
Development of Liquid Based Microemulsion Formulation for Transdermal Drug Delivery
Rajeeva Lochana P.1, Maria Sharon Christy2, Bhavana Manjunatha2,
Ravi Theaj Prakash U.2, *
1School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India
2PG Department of Bioscience, CMR Institute of Management Studies, Bangalore, Karnataka, India
Abstract
Transdermal drugs or “patches” are preferred to oral drugs as it has pharmacological advantages over the oral route and
improved patient acceptability and compliance. Salicylic acid being keratolytic is used on the skin to treat common skin
diseases and foot warts. This study deals with the preparation of formulated gel using castor oil and salicylic acid. Formulation
was prepared by mixing castor and nonyl phenol (surfactant). Evaluation of the formulated gel was observed for its
appearance, homogeneity, pH, spreadability, drug content and antimicrobial activity. According to the obtained results, pH of
castor with drug (6.9) was more efficient when compared to marketed gel (5.9), the formulated drug also showed good
spreadability whereas, the drug content in marketed gel was more efficient. The formulations prepared i.e., castor oil alone as
well as oil with the drug was found to be more effective and showed sensitivity towards certain bacteria and showed no effect
towards fungal species. Therefore from the results obtained, formulated gel was more efficient than marketed gel.
Keywords
Transdermal Drugs, Keratolytic, Surfactant, Castor Oil, Salicylic Acid
Received: August 14, 2016 / Accepted: August 29, 2016 / Published online: September 8, 2016
@ 2016 The Authors. Published by American Institute of Science. This Open Access article is under the CC BY license.
http://creativecommons.org/licenses/by/4.0/
1. Introduction
Transdermal drug delivery system is considered to be one of
the important routes for the delivery of drugs due to its
advantages when compared with other modes of delivery [1].
Several transdermal drugs have been commercialised, which
includes clonidine, estradiol, fentanyl, nicotine, nitro-
glycerine, etc. [2]. Several formulations have been prepared
for delivering these drugs to the system through the skin.
Formulations such as cream, emulsion, gels, lotions, etc. are
being used to improve the bioavailability of the drugs [3].
Emulsions, being the current area of research are being
explored for its efficacy in delivering the drugs through the
skin [4]. Different forms of emulsions are used for the
delivery of drugs, of which microemulsions are used for the
delivery of testosterone [5] and nanoemulsions are used for
the delivery of caffeine [6] and progesterone [7]. Use of
magnetic nanoemulsions in the form of photosensitizers is an
innovative approach for treatment of cancer in the form of
photodynamic therapy [8].
Castor oil has been used and recommended for its powerful
medicinal and curative effects for centuries by physicians.
This is considered to be one of the naturally occurring fatty
oils and about 80-90% of the fatty acids contain ricinolic acid
[9]. Castor oil has a wide range of applications in the field of
medicine where they are used as skin moisturisers such as
lotions for skin and for burns, as creams, gels and herbal
preparations [10], in cosmetics [11], and also for controlled
American Journal of Food Science and Health Vol. 2, No. 5, 2016, pp. 123-128 124
release [12]. A study was carried out at the Meridian Institute
in comparing the absorption efficacy of castor oil when
administered orally and transdermally. Their findings say that
the absorption of castor oil through the skin is more efficient
than the oral administration as the excretion of certain
substances is eliminated.
Salicylic acid has been widely known for its keratolytic
treatment like eczema, psoriasis, etc. [13]. Several reports
are available on the study of salicylic acid including its
metabolism and its bioavailability. One such study deals
with the bioavailability of salicylic acid in a cream
formulation on different skin conditions [14]. Considering
these views, a simple and a novel method has been
proposed for the development of a formulation from castor
oil. The present study deals with the formulation
preparation from castor oil along with salicylic acid and
its evaluation in comparison to marketed salicylic acid gel,
keralyt.
2. Materials and Methods
2.1. Preparation of Formulation
About 20 ml of castor oil was taken. To this 10% of nonyl
phenol was added which acted as a surfactant. The mixture
was homogenized for about 30 mins. 10 ml of acidified water
was added to the mixture. Acidified water was prepared by
adjusting the pH of water to 4.3. After the addition of
acidified water, initial homogenization was carried out for
about 30 min. This was then followed by the final
homogenization at a speed of about 1000 rpm for about 15
min. The obtained emulsion was then evaluated for different
parameters.
2.2. Preparation of Formulation with Salicylic Acid
About 3% salicylic acid was used. The concentration of oil
and the surfactant used are similar to the above prepared
formulation. The drug was dissolved in methanol and loaded
to the oil- surfactant mixture after the preliminary
homogenization of about 30 mins. Then the addition of
acidified water was carried out, followed by initial and final
homogenization. Evaluation was carried out for the said
parameters.
2.3. Evaluation Parameters for the
Prepared Formulation
2.3.1. Appearance
The prepared sample was visually observed for colour,
lucidity, presence of any impurities as it plays an important
role in patient acquiescence.
2.3.2. Homogeneity
The sample prepared was then tested for homogeneity
through visual observation for the presence of aggregates or
any phase separation.
2.3.3. Determination of pH
pH of the sample was determined using a digital pH meter.
This was carried out by adding 2 gm of the prepared sample
to distilled water upon stirring to get a uniform suspension.
The final volume was made upto 50 ml and the pH was
determined.
2.3.4. Spreadability
This was carried out using the apparatus fabricated by
Multimer et al (1956) [15]. This was fabricated by fixing a
glass slide to a wooden block and one end of the upper slide
tied to the weight pan. The prepared sample was placed
between the two slides and a weight of about 250 gm was
placed on the slides for about 10 min to constrict the sample
for obtaining uniform thickness. Weight was then added to
the pan and the time taken to separate the two slides was
observed to evaluate the spreadability. Spreadability was then
calculated using the formula
S = M.L/T
Where, S is spreadability
M is weight tied to upper slide
L is length of glass slide
T is time taken to separate the two slide
2.3.5. Drug Content
About 1 gm of the formulation with salicylic acid was
dissolved in methanol. The final volume was made upto 100
ml in a volumetric flask. This was stirred using a magnetic
stirrer for about 1 hr for complete dissolution. The solution
was then filtered through Whatmann filter paper. The
absorbance was measured at 540 nm against a reagent blank.
2.3.6. Antimicrobial Activity
Antibacterial and antifungal activities were carried out for
the prepared formulation loaded with salicylic acid with
that of marketed gel containing salicylic acid through well
diffusion method. Muller Hinton agar was used. 100 µl of
the sample, prepared formulation and the marketed sample
was loaded into the agar wells. Bacterial cultures of
Bacillus and Micrococcus were used and fungal cultures
like Candida krusie, C. tropicalis, C. albicans,
Trichophyton rubrum and T. mentagrophytes were used.
This was carried out in triplicates.
125 Rajeeva Lochana P. et al.: Development of Liquid Based Microemulsion Formulation for Transdermal Drug Delivery
3. Results and Discussion
Castor oil is obtained from the seeds of the plant Ricinus
communis, having several medicinal uses such as, skin
treatment, constipation problems, arthritis, nasopharyngeal
allergies, treatment of warts, moles, cysts and boosting
immunity. Castor seeds have triglycerides known as
ricinolein. The oil obtained from the dehulled seeds has no
trace of ricinolein, hence non toxic. Lymphocytes are the
immune system's disease-fighting cells and are produced
and stored mainly in the lymphatic tissue, which is a
major factor leading to inflammation and disease. As
castor oil is absorbed through the skin, the lymphocyte
count increases, thereby recovering the immune system.
Castor oil microemulsion was developed for enhancing the
bioavailability of clarithromycin, which has a poor
bioavailability due to first pass metabolism. The results of
this study showed that the oral bioavailability of
clarithromycin was increased on loading the drug within
the castor oil microemulsion [16]. In another study carried
out, castor oil was used as a self emulsifying drug delivery
system for improving the solubility and bioavailability of
telmisartan (hypertensive drug with poor solubility and
poor bioavailability). The results of this study showed a
100% release of the drug even upto 120 mins and also the
bioavailability of the drug was shown to increase [17].
Salicylic acid, being a monohydroxybenzoic acid is
obtained from the willow tree. Like castor oil, salicylic
acid is also known for its curative effects. It is known for
its ability to ease aches, pains and reduce fevers. It is also
used as an anti-inflammatory drug. Similar to other
hydroxy acids, salicylic acid is a key ingredient in many
skin-care products for the treatment of seborrhoeic
dermatitis, acne, psoriasis, calluses, corns, keratosis
pilaris, acanthosis nigricans, ichthyosis and warts. Since
salicylic acid works as bacteriostatic and keratolytic agent,
it causes the cells of the epidermis to shed more easily and
neutralizing bacteria within, preventing pores from
clogging up. Keeping the above benefits of both salicylic
acid and castor oil in view, the formulated gel was
prepared and compared to marketed gel.
The formulations prepared i.e., castor oil alone as well as oil
with the drug were observed to be cream like without any
aggregation and impurities. This is important regarding
patient compliance as it is better applying castor oil cream
rather than oil directly. No phase separation was observed as
the oil was thoroughly homogenized with the surfactant and
the drug. pH of the samples were determined and was
observed to be slightly towards the neutral, since product
with high acid levels have harmful effects on skin so
products with neutral pH is preferred. The pH of formulated
gel (6.9) was neutral compared to the pH of marketed gel
(5.9) which was acidic, making these formulations acceptable
for skin applications.
Spreadability is considered as an important attribute for
topical preparations and also time important with regards to
patient compliance. A formulation is considered to be good if
it requires minimum to spread on the surface [18]. Hence,
these values indicate that small amount of shear is sufficient
for easy spreading. The values obtained for the prepared
formulations were observed to have a good spreadability. The
amount of drug loaded into the formulation was evaluated
and was observed to be 75.2%, whereas for marketed gel, it
was observed to be much higher (96%). Although the
formulated gel had lower drug content, better results were
observed with respect to pH and spreadability compared to
that of the marketed gel.
The formulated gel containing salicylic acid and castor oil
was studied for its in vitro antibacterial and antifungal
activities. Zone of inhibition on the bacterial and fungal
cultures of formulated gel, was significantly higher compared
to that of marketed gel. The results of antimicrobial activity
for the prepared formulation with salicylic acid and the
marketed gel are tabulated. The zone of inhibition against
different bacteria and fungi are tabulated. From the obtained
results it was observed that the formulation prepared from
castor oil and salicylic acid was more sensitive to organisms
such as Bacillus, Micrococcus, C. Krusie and C. tropicalis as
the zone of inhibition with formulated was higher (6.3, 23.6,
11 and 18) when compared with that of marketed gel (5.2,
14.0, 10). Thus from the obtained results, study suggest that
the formulated gel could be used in treating diseases caused
by the test organisms.
Table 1. Evaluation parameters of prepared formulations and the marketed gel.
Appearance Homogeneity pH Spreadability (g.cm/sec) Drug content (%)
Castor oil Cream Good 6.8 64.7 _
Castor oil with drug Cream Good 6.9 62.1 75.2
Marketed gel Transparent Good 5.9 55.3 96
American Journal of Food Science and Health Vol. 2, No. 5, 2016, pp. 123-128 126
Figure 1. Antibacterial activity of castor oil (a), castor oil with drug (b), and marketed gel (c) against Bacillus (A) and Micrococuss (B).
Figure 2. Antifungal activity of castor oil (a), castor oil with drug (b), and marketed gel (c) against C. Krusie (A), C. Tropicalis (B), T. rubrum (C) and T.
mentagrophytes (D).
Table 2. Zone of inhibition for different organisms with the prepared formulation and the marketed gel.
Organism Zone of inhibition of castor oil with drug (mm) Zone of inhibition of marketed gel (mm)
Bacillus 6.3±0.23 5.6±0.17
Micrococcus 23.6±0.46 14±0.27
C. krusie 11±0.11 0
C. tropicalis 18±0.54 10±0.79
T. rubrum 0 0
T. mentagrophytes 0 0
All experiment were performed in triplicates and the results are expressed as mean±S.D (n=3)
127 Rajeeva Lochana P. et al.: Development of Liquid Based Microemulsion Formulation for Transdermal Drug Delivery
Figure 3. Comparision of zone of inhibition of prepared formulation and the marketd gel against different orgamisms.
4. Conclusion
From our study, we can conclude that the formulated gel had
good pH, spreadability and antimicrobial activity. The results
from our study showed better results compared to that of the
marketed gel with respect to their pH, spreadability and
antimicrobial activity. Loading of salicylic acid to the castor
oil further improved its antimicrobial activity compared to
that of the marketed gel. Therefore, through our study it
could be concluded that salicylic acid loaded castor oil could
serve as a potent antimicrobial agent and could be more
applicable for transdermal applications.
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