Hindawi Publishing Corporation

e Scientific World Journal

Volume 2016, Article ID 7394685, 4 pages
http://dx.doi.org/10.1155/2016/7394685

Research Article
Development and Evaluation of Stability of
a Gel Formulation Containing the Monoterpene Borneol

Milla Gabriela Belarmino Dantas,1 Silvio Alan Gonçalves Bomfim Reis,1

Camila Mahara Dias Damasceno,1 Larissa Araújo Rolim,1 Pedro José Rolim-Neto,2
Ferdinando Oliveira Carvalho,3 Lucindo José Quintans-Junior,4
and Jackson Roberto Guedes da Silva Almeida1
1
Center for Studies and Research of Medicinal Plants, Federal University of Vale do São Francisco, 56.304-205 Petrolina, PE, Brazil
2
Federal University of Pernambuco, 50.670-901 Recife, PE, Brazil
3
Federal University of Vale do São Francisco, 56.304-205 Petrolina, PE, Brazil
4
Department of Physiology, Federal University of Sergipe, 49.100-000 São Cristóvão, SE, Brazil

Correspondence should be addressed to Jackson Roberto Guedes da Silva Almeida; jackson.guedes@univasf.edu.br

Received 6 October 2015; Accepted 19 April 2016

Academic Editor: Javed Ali

Copyright © 2016 Milla Gabriela Belarmino Dantas et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the
essential oil of various medicinal plants. It has antibacterial, analgesic, and anti-inflammatory action proven in studies that used oral
and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation
containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected
to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The
prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and
accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol
gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing
statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good
spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal
treatment of skin diseases.

1. Introduction inconveniences of intravenous therapy, and avoids the risks

associated with the varied conditions of absorption, like pH
The topical delivery of drugs is an attractive method for changes, presence of enzymes, and gastric emptying time.
local and systemic treatments and is commonly used in the Furthermore, the bioavailability of the drug is increased and
treatment of inflammatory conditions like dermatological its action occurs directly at the action site [6, 7].
diseases and musculoskeletal injuries [1–3]. Topical appli- A wide variety of pharmaceutical dosage forms can be
cation has many advantages over the conventional dosage used in the delivery system for topical drugs. The most used
forms, especially to avoid some serious systemic adverse ones are gels, creams, and ointments, followed by sprays
effects [4]. and liquid preparations [8, 9]. The topical delivery with
When the drug is delivered topically it can penetrate gels can increase the resistance time of the drug on the
deeper into skin and hence give better absorption [2, 5]. skin and improve the delivery and release of the substance
Topical preparation prevents the metabolism of drug in by increasing the residence time at the injection site [10].
the liver, avoids gastrointestinal disorders and the risks and Furthermore, transdermal delivery of some drugs such as
2 The Scientific World Journal

nonsteroidal anti-inflammatory drugs (NSAIDs) using gel is 2.6. Centrifugation Test. To perform the centrifugation test,
proven effective for a variety of clinical conditions [11]. 10 g of formulation was added in a tapered test tube. In
Borneol (C10 H18 O) is a bicyclic monoterpenoid alcohol centrifugation, the sample gel was subjected to a cycle of
commonly used in traditional Chinese and Indian medicine 3000 rpm for 30 minutes at room temperature. Centrifuga-
and is found in more than 60 products based on medicinal tion was performed with Model Centribio 80-2B equipment.
plants [12–14]. The borneol is extracted from the essential oil
of various medicinal plants and has the ability to accelerate 2.7. Spreadability. The spreadability of the BG5 was measured
the opening of the blood-brain barrier and increase the by spreading of 0.5 g of the gel on a circle of 2 cm diameter
bioavailability of drugs in the brain tissue [15, 16]. It has premarked on a glass plate and then a second glass plate was
antibacterial, analgesic, and anti-inflammatory action proven employed. Half kilogram of weight was permitted to rest on
in studies that used oral and intraperitoneal applications of the upper glass plate for 5 min [19, 20]. The diameter of the
this monoterpene in mice [17, 18]. circle after spreading of the gel was determined.
Although the easy borneol penetration into the nervous
tissue is reported and it is a potent analgesic and anti- 2.8. Conductivity and pH Analysis. The pH and conductiv-
inflammatory, there are no reports in the literature about ity of BG5 formulation were determined by using digital
borneol penetration of the skin and its topical or transdermal pH meter (MSTecnopon equip. Special LTDA). The glass
effect. Therefore, the aim of this study was to develop an electrode was calibrated with the solutions determined for
effective, stable topical gel containing borneol 5% (BG5). the equipment (pH of 4.00 and 7.00), and the conductivity
measurement was done in millivolts (mV). The preparation
2. Materials and Methods was left for about 15 min for attaining equilibrium while mea-
suring. The analysis of pH and conductivity of formulation
2.1. Materials. The borneol was purchased from Sigma- were done in triplicate and average values were calculated.
Aldrich, and carbopol 940, EDTA, methylparaben, and
triethanolamine were purchased from Via Farma. 2.9. Viscosity Study. The viscosity measurement of the bor-
neol gel was performed with a Viscometer (Quimis MOD
2.2. Preparation of Borneol Gel. The exact amount of carbopol
0860M21). The gel was rotated at 10, 20, 30, 40, 50, and 60
940 (1%), propylene glycol (7%), and methylparaben (0.1%)
rotations per minute. At each speed, the corresponding dial
was dispersed in distilled water. The carbopol dispersion
reading was noted.
was kept at rest for 24 hours to allow for the complete
swelling. Then the blended carbopol was mixed with contin-
2.10. Statistical Analysis. The BG5 formulation was tested
uous stirring, ultrasound, and hot plate to form gel aspect.
in triplicate, and each analysis was duplicated. Effects of
Dispersion obtained was neutralized with required quantity
formulation variables after freeze-thaw cycle were tested for
of triethanolamine to obtain pH 5.0 to 5.5. The carbopol
significance by using Student’s 𝑡-test using Graph Pad Prism
remained in a plastic jar for a week at room temperature.
software 5.0 version (Graph Pad Software Inc., San Diego, CA,
Then, a concentration corresponding to 5% of borneol was
USA) and the 𝑝 values < 0.05 were considered.
diluted with propylene glycol and added to the carbopol. The
BG5 was stored in a glass jar and kept at room temperature
for 8 months for physical and chemistry analysis. 3. Results and Discussion

2.3. Macroscopic Analysis of Formulation. The prepared BG5 The borneol gel formulation (BG5) was assessed for its
formulation was inspected visually for its color, homogeneity, macroscopic characteristics and qualities such as color,
consistency, and spreadability. The clarity was determined by aspect, and aroma. The borneol gel formulation has a smooth
using the natural light and all the macroscopic analyses were texture and white color transparent and homogeneous and
realized comparing with carbopol. characteristic odor of borneol extract. The BG5 character-
istics remained similar eight months after development and
2.4. Accelerated Stability and Physicochemical Analysis of there was no difference in aspect of BG5 before and after
Borneol Gel. The BG5 was submitted to accelerated stability freeze-thaw cycle.
tests. The gel was kept at room temperature (20–25∘ C) for The pH values of the BG5 were found to be in the range
evaluation to color, odor, pH, viscosity, and conductivity. For from 3.95 ± 0.01 to 3.83 ± 0.03, which was expected since
analysis of the resistance to freeze-thaw cycle, the BG5 was the carbopol was formulated with pH between 5 and 5.5
kept at a temperature of 4∘ C and 40∘ C for 12 days. The tests because these are values sufficient to obtain a good viscosity
were performed eight months after the production of the and clarity of the gel [21]. Furthermore, the borneol is also
formulation. Each test was done in triplicate with samples of considered acidic [22]. This pH value showed that the BG5
30 grams each. probably would not produce skin irritation. The conductivity
values of BG5 also remained stable; statistical difference in
2.5. Freeze-Thaw Cycle. The BG5 sample was subjected to pH values and conductivity before and after freezing-thaw
freeze and thaw cycle; the test was performed in 12 days with cycle was not verified. Hence, the prepared borneol gel is
six cycles. In each cycle, the substance remained in a parti- suitable for topical application. Table 1 shows the physical and
cular temperature for a period of 24 hours. The temperature chemical values of BG5 before and after twelve days of the
in the refrigerator was 5 ± 2∘ C and 40∘ C in the greenhouse. freeze and thaw cycle.
The Scientific World Journal 3

Table 1: Results of evaluation of the preliminary stability of borneol gel 5% before and after the freeze-thaw cycle.

Sample Appearance pH Conductivity Centrifugation

BG5% before Homogeneous, transparent, colorless 3.95 ± 0.01 186.15 ± 0.35 mV No noticeable instability in the formulation.
BG5% after Homogeneous, transparent, colorless 3.83 ± 0.03 171.3 ± 1.27 mV No noticeable instability in the formulation.
Values are mean ± standard deviation.

60000 Therefore, it was concluded that the formulation could be

50000 very promising alternative for the topical or transdermal
treatment. However, further preclinical, clinical, and long-
40000 term stability studies should be required.
30000
Competing Interests
20000

10000 The authors declare that they have no competing interests.

0
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