You are on page 1of 7

Drug Development and Industrial Pharmacy, 2013; 39(10): 1540–1546

© 2013 Informa Healthcare USA, Inc.


ISSN 0363-9045 print/ISSN 1520-5762 online
DOI: 10.3109/03639045.2012.719902

Research Article

 etermination of required hydrophilic–lipophilic balance of


D
citronella oil and development of stable cream formulation
Jaya Gopal Meher1, Narayan Prasad Yadav1, Jagat Jyoti Sahu2, and Priyam Sinha1
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

1
Herbal Medicinal Product Department, Central Institute of Medicinal and Aromatic Plants (Council of Scientific and
Industrial Research), P.O. CIMAP, Lucknow, UP, India and 2Gayatri Institute of Science and Technology, Biju Patnaik
University of Technology, Rourkela (Odisha) India

Abstract
Context: Citronella oil is reported to have excellent mosquito-repellent activity. To develop a stable cream formulation
(emulsion), its hydrophilic–lipophilic balance (HLB) value is important.
Objective: To determine required hydrophilic–lipophilic balance (rHLB) value of citronella oil and to develop stable
cream formulation.
Materials and Methods: Emulsions of citronella oil were prepared by phase inversion temperature technique using
water, Tween 80 and Span 80. A first series of 11 emulsions with HLB values ranging from 5.0 to 15.0 and a second series
of eight emulsions with smaller interval in HLB values from 11.0 to 13.8 were prepared. Emulsions were evaluated
For personal use only.

for creaming index, droplet size and turbidity to determine rHLB. Utilizing determined rHLB, citronella oil cream
was formulated and evaluated for different texture parameters. rHLB of light liquid paraffin was also determined for
validation of methodology.
Results: rHLB of light liquid paraffin and citronella oil was determined to be 11.80 and 12.60, respectively. Stable
citronella oil cream was developed with 10% emulsifier blend. Texture parameters were found to be consistent over
the entire storage period.
Discussion: Creaming index, droplet diameter, percent increase in droplet diameter and turbidity are the established
parameters to determine rHLB and to develop stable emulsion. Emulsions with optimum emulsifier concentration
resulted in less percentage creaming index, smallest droplet, less percentage increase in droplet diameter and
highest turbidity. Texture properties evaluation ensures the stability of the developed cream.
Conclusion: rHLB value of citronella oil was found 12.6 and a stable cream was formulated utilizing determined rHLB.
Keywords:  Emulsion, emulsifier, creaming index, droplet size, turbidity, texture analysis

Introduction in emulsion such as light liquid paraffin, cetyl/stearyl


Most of the pharmaceutical as well as cosmetic semisolid alcohol, stearic acid, paraffin wax, Tween series, Span
formulations are biphasic systems (emulsion, cream and series, glycerol stearates and many more are reported
lotion), where hydrophilic–lipophilic balance (HLB) plays in literature; whereas aromatic oils are still not properly
a vital role by managing tension between two immiscible investigated and reported7.
liquids at their interface1–4. Exact knowledge of required Citronella oil is an aromatic oil from Cymbopogon
HLB (rHLB) value of different ingredients in an emulsion spp. It is reported to be an excellent mosquito-repellent
guides towards the determination of rHLB of the system aromatic oil8,9. Candles and incense containing citronella
(oil phase of formulation), which ultimately help in the oil are sold as insect repellent in some countries10,11.
development of a stable formulation5,6. Fortunately rHLB It has pale yellow to brownish yellow color with a
of most of the ingredients including emulsifiers used strong pungent/fruity odor. Different physicochemical

Address for Correspondence:  Dr. Narayan Prasad Yadav, Central Institute of Medicinal and Aromatic Plants (Council of Scientific and
Industrial Research), P. O. CIMAP, Lucknow (U.P.) India 226015. Tel.: +91-522-2718657. Fax: +91-522-2342666. E-mail: npyadav@gmail.com
(Received 03 March 2012; revised 29 June 2012; accepted 06 August 2012)

1540
rHLB of citronella oil and cream formulation  1541
properties of citronella oil, which is insoluble in water are Table 1.  Hydrophilic–lipophilic balance spread sheet of emulsion
Flash Point: 77°C, Boiling Point: 200°C, Specific Gravity: preparation.
0.897, Refractive Index (25°C): 1.4660–1.4750 and Optical Formulation
Rotation: −5° to 0°12,13. Some conventional and novel drug Formulation Span Tween (Light liquid
(Citronella oil) HLB 80 (%) 80 (%) paraffin)
delivery system of citronella oil for mosquito-repellent
First series emulsions
activity has been reported in the literature14–16.
 CE1 5.0 93.46 06.54 LE1
In the present study, a pharmaceutically and cosmeti-
 CE2 6.0 84.12 15.88 LE2
cally elegant cream formulation of citronella oil with dif-
 CE3 7.0 74.77 25.23 LE3
ferent cream bases was attempted to develop17,18. During
 CE4 8.0 65.43 34.57 LE4
the formulation development process, difficulty in selec-
 CE5 9.0 56.08 43.92 LE5
tion of suitable emulsifiers was experienced to produce a
 CE6 10.0 46.73 53.27 LE6
stable emulsion. These complications further guided to
 CE7 11.0 37.39 62.61 LE7
determine the rHLB value of citronella oil, which is not
 CE8 12.0 28.04 71.96 LE8
reported in the literature. Therefore in the present inves-
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

 CE9 13.0 18.70 81.30 LE9


tigation attempts have been made for the determination
 CE10 14.0 09.35 90.65 LE10
of rHLB value of citronella oil. To ensure correctness of
 CE11 15.0 00.00 100.00 LE11
the applied methodology, the rHLB value of light liquid
Second series emulsions
paraffin was also determined simultaneously, which is
 CE13 11.0 37.39 62.61 LE13
reported to be 11 ± 16,19,20.
 CE14 11.4 33.65 66.35 LE14
Utilizing the determined rHLB of citronella oil, cream
 CE15 11.8 29.91 70.09 LE15
formulation was developed and evaluated for differ-
 CE16 12.2 26.17 73.83 LE16
ent texture parameters such as firmness, adhesiveness,
 CE17 12.6 22.43 77.83 LE17
extrudability, spreadability, consistency and cohesive-  CE18 13.0 18.70 81.30 LE18
ness for a period of 90 days. These parameters help to  CE19 13.4 14.96 85.04 LE19
ensure reproducible quality of a specific product.  CE20 13.8 11.22 88.78 LE20
CE, citronella oil emulsion; LE, light liquid paraffin emulsion;
For personal use only.

Materials and methods HLB, hydrophilic–lipophilic balance.

Materials 11.0–13.8 were formulated separately for citronella oil


Citronella oil was obtained from Central Institute of and light liquid paraffin (Table 1).
Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow.
Light liquid paraffin, Tween 80, Span 80, stearyl alcohol, Physical evaluation
cetyl alcohol, hard paraffin wax were procured from SD The first series of 11 emulsions were physically evaluated
Fine Chem Limited, Mumbai. Glycerol monostearate for any visual changes in appearance and color or insta-
(GMS) was procured from Central Drug House Pvt. Ltd. bilities such as phase separation, creaming or coales-
New Delhi. All the ingredients were of Analytical Reagent cence at regular interval of time (each alternate day) for
grade and used as received. 30 days. Creaming index (CI) of all the emulsions was
determined21. Based on the above investigations, most
Methods stable emulsions were identified. Further a second series
Preparation of emulsion of emulsions were prepared using smaller intervals in
For the determination of rHLB of citronella oil/light HLB range of 11.0–13.8. The Second series of eight emul-
liquid paraffin, 5% of the respective material was taken sions were subjected to other evaluation parameters.
as oil phase. Blend of Tween 80 (HLB 15.0) and Span 80
(HLB 4.3) in different ratio was chosen as emulsifier at Creaming index (CI)
3% concentration and 92% water was taken as the con- CI was determined by taking the ratio of total height of
tinuous/aqueous phase7,21. Phase inversion temperature cream (HC) layer and total height of emulsion (HE) in
technique was adopted for the preparation of emul- the storage container (plastic bottle with 2 cm diameter
sions. Emulsifier blends which could produce HLB in the and 8 cm height). CI was recorded on 3rd, 5th, 10th, 15th
range of 5–15 were prepared for both citronella oil and and 30th day.
light liquid paraffin separately in first series of emulsion
%CI = ( H C / H E ) × 100
preparation (Table 1). The required amount of Span 80
was dissolved in the oil phase and Tween 80 in the aque-
ous phase. Both the phases were maintained at 50–55°C. Droplet size analysis
Aqueous phase was poured in to the oil phase with gentle Droplet size measurement of the emulsions was per-
stirring at the same temperature. Stirring was continued formed with an optical microscope (Unilab optical
for 15 min at 2000 rotations per minute (RPM) with the microscope) fitted with X40 objective and a standard-
help of an over head stirrer (Ika Eurostar). In second ized X10 ocular micrometer scale. Sampling was carried
series of preparation, eight emulsions in HLB range of out after a gentle shaking of the emulsion container to

© 2013 Informa Healthcare USA, Inc.


1542  J. G. Meher et al.
ensure even dispersion of the droplets. Each emulsion Evaluation of citronella oil cream formulation
was diluted to 100 times using aqueous propylene gly- Citronella oil cream formulation (CR4) was evaluated for
col22. Not less than 400 droplets were measured covering different texture parameters viz. cream firmness, adhe-
at least six fields of view and the mean droplet diameter siveness, cohesiveness, consistency, spreadability and
(MDD) was calculated. The percent increase in MDD (X) extrudability by using CT3 Texture Analyzer (Brookfield
of each emulsion formulation after 30 days was deter- Engineering Laboratories, USA). Test parameters
mined by the following formula. (given in Supplementary Table S1) were selected as per
individual test requirement. All the graphs (shown in
X % = 100 ( X 2 − X 1 ) / X 1 Supplementary Figure S1) and data were generated using
Texture Pro CT V1.3 Software and formulation was evalu-
Where X1 and X2 are MDD of the emulsion, on day 1 ated in triplicate.
and day 30 respectively. Sampling was done in triplicate
for this experiment.
Results
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

Turbidity analysis Creaming index


Five milliliter of each emulsion preparation was with- Percent CI of citronella oil and light liquid paraffin emul-
drawn into colorless glass vials (15-mL Borosil culture sions stored at room temperature have been shown in
tubes). The vials were stored undisturbed at room tem- Table 3. Citronella oil emulsions from HLB 5 to 9 (CE1 to
perature (25 ± 1°C) and on the 7th day, 0.5 mL sample was CE6) showed separation of aqueous and oil layers within
gently withdrawn from the base of the tube using 1 mL 10–30 days. No phase separation was observed for emul-
syringe. The sample was diluted to 25 mL with double sions of HLB 11–13 (CE7–CE9) and CI was determined
distilled water and the percent transmission (%T) was to be lowest (1.0–1.1% on day 3) for these emulsions;
measured at 600 nm with the help of UV-Visible spectro- whereas for HLB value of 14 and 15 (CE10, CE11), phase
photometer (Molecular Device) keeping blank control at separation was observed on day 30 and CI was found to
100% transmission. For this experiment, sampling was be comparatively higher (1.0–1.3% on day 3). CE7 showed
done in triplicate, and turbidity of the diluted sample was highest CI (10.2%) and CE9 showed lowest CI (9.8%) on
calculated by the following formula5,21. day 30. For light liquid paraffin emulsions, phase sepa-
For personal use only.

ration was seen in emulsions of HLB 5–9 (LE1–LE5) and


Turbidity = 100 − %T 14–15 (LE10, LE11). Emulsions were comparatively
stable in the HLB range of 10 to 13 (LE6 to LE9). Lowest
The results obtained are average of three values.

Formulation of citronella oil cream Table 3.  Percent creaming index of citronella oil and light liquid
Based on the above investigations, rHLB value of cit- paraffin emulsions stored at room temperature.
ronella oil was determined and further utilized in the Emulsions Day 3 Day 5 Day 10 Day 15 Day 30
development of cream formulations which are shown in CE1 2.8 6.6 PS PS PS
Table 2. Oil phase of the cream containing light liquid CE2 2.4 6.3 PS PS PS
paraffin, paraffin wax, cetyl alcohol, stearyl alcohol CE3 2.1 6.1 PS PS PS
and GMS was heated up to 65°C for melting the ingre- CE4 1.9 5.8 PS PS PS
dients. Aqueous phase containing Tween 80 and water CE5 1.8 4.4 PS PS PS
was heated up to 50–55°C. Citronella oil was added to CE6 1.5 4.3 8.4 10.6 PS
oil phase when the temperature came down to 50–55°C CE7 1.1 3.8 6.8 8.3 10.2
and finally aqueous phase was mixed to the oil phase CE8 1.0 3.7 6.6 8.0 10.0
with constant stirring. The mixture was stirred for about CE9 1.0 3.7 6.2 8.0 9.8
30 min until homogenous cream was prepared7,21,24. CE10 1.0 3.9 6.2 8.2 PS
CE11 1.3 3.8 6.4 8.3 PS
Table 2.  Citronella oil cream formulationsa. LE1 2.9 5.9 PS PS PS
Formulations/Ingredients (%) CR1 CR2 CR3 CR4 LE2 2.7 5.9 PS PS PS
Light liquid paraffin 8.00 8.00 8.00 8.00 LE3 2.4 5.8 PS PS PS
Citronella oil 2.00 2.00 2.00 2.00 LE4 1.9 5.5 9.8 PS PS
Paraffin wax 3.00 3.00 3.00 3.00 LE5 1.8 4.6 8.8 10.2 PS
Cetyl alcohol 2.00 2.00 2.00 2.00 LE6 1.2 3.2 8.4 8.8 10.4
Stearyl alcohol 2.00 2.00 2.00 2.00 LE7 1.0 3.2 8.1 7.4 9.2
Tween 80 2.95 4.42 5.90 7.37 LE8 1.1 3.3 8.2 7.4 9.4
GMS 1.05 1.58 2.10 2.63 LE9 1.3 3.6 8.5 8.0 10.2
Water (up to 100 mL) q.s. q.s. q.s. q.s. LE10 1.3 3.5 8.6 8.2 PS
a
rHLB of oil phase in citronella oil cream formulation: 12.56. LE11 1.5 3.4 8.8 PS PS
Surfactant Blend is GMS: Tween 80 = 1:2.8. CE, citronella emulsion; LE, light liquid paraffin emulsion; PS,
GMS, glycerol monostearate; q.s, quantity sufficient; CR, cream. phase separation.

 Drug Development and Industrial Pharmacy


rHLB of citronella oil and cream formulation  1543
CI was shown by LE7 (1.0%) and highest by LE6 (10.4%) rHLB and cream formulation
on day 30. Based on the investigations viz. droplet size analysis,
turbidity and CI, rHLB value of citronella oil and light liquid
Droplet size paraffin was determined to be 12.6 and 11.8, respectively
MDD of citronella oil emulsions and light liquid paraffin (Table 4). By utilizing experimentally determined rHLB of
emulsions over the period of 30 days has been depicted citronella oil and light liquid paraffin, rHLB of the oil phase
in Figures 1 and 2, respectively and Figure 3 shows the of cream formulation was calculated and found to be 12.5623.
percent increase in MDD. On day 1, MDD of all citronella In view of the calculated rHLB value of oil phase, com-
oil emulsions were found to be 4.32 ± 0.09 µm (CE17) to bination of glycerol monostearate (HLB = 5.5) and Tween
4.73 ± 0.13 µm (CE20). Considerable increase of MDD 80 (HLB = 15.0) was used as emulsifier blend in the ratio
was observed upon storage over a period of 30 days. of 1:2.823. Cream with 10% (CR4) emulsifier blend con-
Lowest and highest MDD were found to be 5.03 ± 0.09 centration was formulated successfully, whereas with 4%
µm (CE17) and 6.66 ± 0.11 µm (CE13), respectively. For (CR1), 6% (CR2) and 8% (CR3) of emulsifier blend, emul-
citronella oil emulsions, CE17 (HLB = 12.6) showed low-
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

sification could not be achieved.


est MDD over 30 days. On day 1, MDD of all light liquid
paraffin emulsions were determined to be 4.12 ± 0.19 µm Texture profile
(LE15) to 4.61 ± 0.07 µm (LE16), whereas on 30th day drop- Texture profile analysis results of citronella oil cream for-
let size increased to 5.24 ± 0.14 µm (LE15) and 7.27 ± 0.2 mulation is shown in Table 5. Firmness was found to be
µm (LE20). LE15 (HLB = 11.8) showed lowest MDD 6 ± 0.25 g on day one, whereas it was increased to 7 ± 0.55 g
for light liquid paraffin emulsions over 30 days. CE17 over a period of 90 days. Consistency was determined to
showed 16.43% and CE14 exhibited 44.61% increase in be 0.8 ± 0.04 mJ on the day of formulation and for the next 3
MDD, whereas 27.18% and 63.73% increase in MDD was months it was found to be 0.9 ± 0.06 mJ. Adhesiveness was
recorded for LE15 and LE20, respectively. determined to be 1 ± 0.22 g on the day of formulation and
increased to 1.5 ± 0.42 g over next 3 months. Cohesiveness
Turbidity was found to be within 0.94 ± 0.01 and 0.99 ± 0.02 on
Turbidity of citronella oil emulsions and light liquid the day of formulation and over 90 days respectively.
paraffin emulsions has been exhibited in Figure 4. For Spreadability of cream was found to be 1.8 ± 0.04 mJ over
For personal use only.

citronella oil emulsions turbidity was found to be in the entire 3 months. Extrudability was found to be 25.1 ± 1.04
range of 89.12 ± 2.4 (CE17, HLB = 12.6) and 60.14 ± 2.1 mJ on the day of formulation whereas it was increased to
(CE19, HLB = 13.4) whereas for light liquid paraffin emul- 25.8 ± 1.45 mJ over a period of 90 days.
sions it was found to be 91.2 ± 3.6 (LE15, HLB = 11.8) and
62.9 ± 2.8 (LE19, HLB = 13.4).
Discussion
Creaming index
Regardless of emulsifier concentration and/or combi-
nation, creaming is a natural phenomenon in biphasic
systems and is an indication of destabilization25–27. It
gives a preliminary idea of nearest range of stable emul-
sions which may be useful for determining the rHLB. All
the emulsions (Citronella oil emulsions and light liquid
paraffin emulsions) were studied for creaming for the
period of 30 days and their percent CI was determined
(Table 3). During first two days creaming was not seen
for any of the formulated emulsions, whereas 3rd day
Figure 1.  Mean droplet diameter of citronella oil emulsions over a onwards increase in creaming was observed with time.
period of 30 days. Mean value ± SEM, n = 3.
It was also observed that the CI was decreased with the
increase in HLB value of the emulsion. After 30 days cit-
ronella oil emulsions with HLB value 11–13 were found
stable and rest of the emulsions were separated into two
different layers. These results indicate the rHLB of citro-
nella oil lies in between 11 and 13 (CE7–CE9), hence a
second series of eight emulsions with HLB value 11.0–
13.8 (CE13–CE20, Table 1) were prepared and subjected
to other evaluation parameters viz. particle size and
turbidity analysis. Similarly, light liquid paraffin emul-
sions in the HLB range of 10–13 were found compara-
Figure 2.  Mean droplet diameter of light liquid paraffin emulsions tively stable and the same evaluations were performed
over a period of 30 days. Mean value ± SEM, n = 3. for these emulsions.

© 2013 Informa Healthcare USA, Inc.


1544  J. G. Meher et al.

Figure 3.  Percent increase in mean droplet diameter of citronella oil emulsions and light liquid paraffin emulsions on day 30.

particle size and hence negatively influences the stability


Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

of emulsion22. Suitable combination of emulsifiers and


their concentration play a vital role in minimizing the
surface tension of two phases (aqueous and oil phase),
consequently minimize the coalescence of droplets28.
Based on the above fact, it is considered that emulsions
(specific HLB) showing smallest particle size is close to
the required HLB of oil. Droplet size for both citronella
oil and light liquid paraffin emulsions was analyzed over
30 days, and MDD was determined which is depicted in
Figures 1 and 2. Interpretation of stability of the emul-
sions based on droplet size investigation at initial days
may be biased; hence it was studied over the storage
Figure 4. Turbidity of citronella oil emulsions and light liquid period of 30 days. It was found that citronella oil emul-
For personal use only.

paraffin emulsions. sions, CE17 (HLB = 12.6) and light liquid paraffin emul-
sions, LE15 (HLB = 11.8) showed minimal droplet size
Table 4.  Required HLB of citronella oil and light liquid paraffin over the course of investigation. Percent increase in
(experimentally determined). MDD, over storage is another useful indicator for access-
Methods for determination of HLB
ing the stability of emulsions, because suitable emulsifier
Percent increase Percent
results in to minimum increase in droplet diameter. As
Oils MDD in MDD Turbidity CI
depicted in Figure 3, CE17 and LE15 have shown 16.43
Citronella oil 12.6 12.6 12.6 12.0, 13.0,
14.0 and 27.18% increase in MDD which suggests that these
Light liquid 11.8 11.8 11.8 11.0 emulsions are close to rHLB of the respective oils.
paraffin
MDD, mean droplet diameter; CI, creaming index; HLB, Turbidity
hydrophilic–lipophilic balance. Rate of creaming in a polydisperse system can be
defined as:
Table 5.  Texture analysis of stable citronella oil cream formulation
(CR4).
 8π 
Duration (Days) u = ∑i gni ri5 (d1 − d2 )
Parameters 0 30 60 90  27ηV 
Consistency 0.8 ± 0.040 0.9 ± 0.025 0.9 ± 0.038 0.9 ± 0.064
(mJ) Where ni is number of droplets, ri is the radius of drop-
Firmness (g) 6.0 ± 0.25 6.0 ± 0.45 7.0 ± 0.15 7.0 ± 0.55 lets, V is total volume of dispersed phase, η is viscosity
Spreadability 1.8 ± 0.042 1.8 ± 0.045 1.8 ± 0.034 1.8 ± 0.024 of emulsion, g is acceleration due to gravity and (d1–d2)
(mJ) is the density difference between the dispersed and con-
Adhesiveness 1.0 ± 0.22 1.5 ± 0.15 1.5 ± 0.42 1.5 ± 0.32 tinuous phases28. If all the parameters are kept constant,
(g) rate of creaming will depend on droplet diameter. Bigger
Cohesiveness 0.94 ± 0.011 0.99 ± 0.018 0.99 ± 0.022 0.99 ± 0.025 droplet causes more creaming, which leads to poor sta-
Extrudability 25.1 ± 1.04 25.1 ± 1.25 25.8 ± 1.45 25.8 ± 0.95 bility of emulsion, whereas smaller droplet causes slower
(mJ)
creaming, hence better stability is the consequence. The
Mean value ± SEM, n = 3.
emulsions with smaller droplet are turbid in comparison
Droplet size to bigger droplet emulsion; which is determined by tur-
Droplets of dispersed phase have the tendency to bidimetry method29. For citronella oil emulsions highest
coalesce over the storage period, which increases the turbidity was found to be 89.12 ± 2.4 (CE 17, HLB = 12.6),
whereas for light liquid paraffin emulsion it was 91.2 ± 3.6

 Drug Development and Industrial Pharmacy


rHLB of citronella oil and cream formulation  1545
(LE15, HLB = 11.8). Based on the theory discussed above Adhesiveness, which can be defined as the maximum
and the obtained results it was interpreted that the rHLB force required for overcoming the attractive force
might be close to 12.6 and 11.8 for citronella oil and light between surface and sample, was characterized as a
liquid paraffin respectively. While comparing the results measure for stickiness of the sample30,31. CR4 cream
of turbidity and particle size it was observed that turbid- formulation was found to require 1 ± 0.22–1.5 ± 0.42 g
ity was found maximum, at the same HLB value at which force to get separated from the surface. Cohesiveness
the MDD was determined to be minimum. is another parameter which indicates the strength of
internal bonds that is ultimately responsible for overall
rHLB and cream formulation elegance of the cream. Mathematically it is the ratio of
Based on the theory that emulsions with optimum emul- hardness work done at two cycles30,31. For CR4 cohesive-
sifier concentration will result in smallest MDD, less per- ness was found to be within 0.94 ± 0.01–0.99 ± 0.02. The
cent increase in MDD over storage and highest turbidity, values determined for different evaluation parameters
the required HLB of citronella oil was determined5–7,28. were reproducible over the entire storage period of time
For the validation of the methodologies, rHLB of light and hence can be utilized as formulation finger print to
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

liquid paraffin was also determined simultaneously. ensure consistent quality of citronella oil cream formu-
Based on the above mentioned evaluation parameters lation. Table 5 exhibits the texture analysis data of citro-
rHLB of citronella oil and light liquid paraffin was found nella oil cream formulation.
to be 12.6 and 11.8, respectively. Reported rHLB of the Spreadability of cream, lotion or gel depends upon the
later is in the range of 11 ± 119,20. Experimentally deter- ingredients used33,34. For instance products with rich con-
mined rHLB value of both citronella oil and light liquid tent of lipid/high molecular weight wax are less spread-
paraffin by three different methods is shown in Table 4. able because of high viscosity and surface tension. The
After the determination of rHLB of citronella oil, it was male female probe (TA15/100: conical probe, Brookfield
implemented for the development of cream formulation. Engineering Laboratories, Inc. USA) for spreadabil-
Blend of Glycerol monostearate and Tween 80 in the ity evaluation is an imitation for human perception
ratio of 1:2.8 at 10% concentration could produce stable of spreading any cream over skin surface30,31. Certain
emulsion. These observations suggest that not only the amount of work is done by these probes to penetrate the
rHLB of oil phase but the appropriate concentration of sample (cream/gel/semisolid products) up to a definite
For personal use only.

emulsifiers is also crucial for the stable cream formula- depth and the energy (mJ) required for this purpose
tion. Further it was found that emulsifier with higher define the spreadability of the formulation. Higher firm-
HLB value (e.g. Sodium lauryl sulfate, HLB 40) could ness and hardness value implies a less spreadability and
stabilize the emulsion at lower concentration. Therefore vice versa. Spreadability of citronella oil cream was found
it can be inferred that the ratio and percentage of specific to be 1.8 ± 0.02 mJ at 25 ± 1°C. Table 5 exhibits the spread-
emulsifier blend is unique to the developed formulation. ability data of citronella oil cream formulation.
If the emulsifiers with different HLB value are used, the Packaging of formulations is an important issue for
concentration of emulsifiers to stabilize the same emul- overall acceptance of product by end users. From con-
sion may vary. sumer’s compliance point of view, extrusion of cream/
lotion/gel from the container (tube, box) is a major con-
Texture profile cern35. A good product with poor extrudability may not
Consistency, firmness, adhesiveness and cohesiveness be acceptable. CR4 was evaluated for forward extrusion
are the different texture parameters that define a specific with TA-DEC probe and work done in extrusion was
type of formulation and imitate human perception for determined to be 25.1 ± 1.04–25.8 ± 1.45 mJ. It was found
any cosmetic/medicated products30,31. These parameters that forward extrusion of citronella oil cream was smooth
do not have any fixed selection criteria or any official and continuous. Table 5 exhibits the extrudability data of
standards (pharmacopoeial/regulatory), but based on citronella oil cream formulation. All the texture parame-
the product specific requirement, these parameters can ters of optimized cream formulation CR4 were reproduc-
be characterized and standardized. ible and consistence over the storage period of 3 months.
Firmness of any semisolid formulation is a reflection of
its hardness. It is the maximum positive force to deform/
Conclusion
penetrate the sample with finger30–32. Based on the type
of product, firmness should be defined. For citronella oil Based on the theory that emulsions with optimum emul-
cream, firmness was found to be 6 ± 0.25–7 ± 0.55 g over a sifier concentration result in smallest MDD, less percent
period of 3 months. Consistency of the sample is related increase in MDD upon storage and highest turbidity value,
to the work done to hardness. For this cream, consistency the rHLB of citronella oil and light liquid paraffin was
was found to be similar over a period of 3 months as indi- found to be 12.6 and 11.8, respectively. Cosmetically ele-
cated by the work done to hardness, which was ranging gant citronella oil cream was developed with 10% emulsi-
from 0.8 ± 0.04 to 0.9 ± 0.06 mJ. fier (glycerol monostearate and Tween 80 in the ratio of 1:
Stickiness of semisolid formulation is a major issue 2.8) concentration. Citronella oil cream was evaluated for
for its acceptance, especially for cosmetic products. different texture parameters viz. consistency (0.8 ± 0.040

© 2013 Informa Healthcare USA, Inc.


1546  J. G. Meher et al.
mJ), firmness (6.0 ± 0.25 g), adhesiveness (1.0 ± 0.22 g), 13. Material safety data sheet Citronella Oil MSDS [online]
cohesiveness (0.94 ± 0.011), spreadability (1.8 ± 0.042 mJ) 2005;1–5. Available at: http://www.sciencelab.com/msds.
php?msdsId=9923497. Accessed on 25 April 2012.
and extrudability (25.1 ± 1.04 mJ) for quality control of 14. Solomon B, Sahle FF, Gebre-Mariam T, Asres K, Neubert RH.
developed cream. Normally in practice, achievement of (2012). Microencapsulation of citronella oil for mosquito-repellent
required concentration of emulsifier blend is based on application: formulation and in vitro permeation studies. Eur J
trial and error methods, but there is a need of evolving Pharm Biopharm, 80:61–66.
the methods/hypothesis/formulae or law for determin- 15. Specos MM, García JJ, Tornesello J, Marino P, Vecchia MD,

Tesoriero MV et al. (2010). Microencapsulated citronella oil for
ing emulsifier concentration in the development of a mosquito repellent finishing of cotton textiles. Trans R Soc Trop
stable cream formulation. Med Hyg, 104:653–658.
16. Usawadee S, Onanong N, Napaporn U, Satit P, Apinan S, Uracha
R. (2009). Characterization and mosquito repellent activity of
Acknowledgement citronella oil nanoemulsion. Int J Pharm, 372:105–111.
17. Baudonnet L, Grossiord JL, Rodriguez F. (2004). Physicochemical
Authors are highly thankful to Central Institute of characterization and in vitro release of salicylic acid from O/W
Medicinal and Aromatic Plants-Council of Scientific and
Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by RMIT University on 09/11/13

emulsions prepared with Montanov 68: effect of formulation


Industrial Research (CIMAP-CSIR), India for providing parameters. Drug Dev Ind Pharm, 30:975–984.
infrastructure facilities and financial support for carrying 18. Krajisnik D, Milic J. (2003). Polymer-stabilized emulsion systems:
out this work. structural characteristics and physical stability evaluation. Drug
Dev Ind Pharm, 29:701–711.
19. Lund W. (1994). The pharmaceutical codex, principles and practice
Declaration of interest of pharmaceutics. London: Pharmaceutical Press, 86–87.
20. Prinderre P, Piccerelle Ph, Cauture E, Kalantzis G, Reynier JP,
The authors report no declarations of interest. Joachim J. (1998). Formulation and evaluation of o/w emulsion
using experimental design. Int J Pharm, 163:73–79.
21. Ferreira MR, Santiago RR, de Souza TP, Egito ES, Oliveira EE,
Soares LA. (2010). Development and evaluation of emulsions
References from Carapa guianensis (Andiroba) oil. AAPS PharmSciTech,
  1. Griffin WC. (1949). Classification of surface active agents by “HLB”. 11:1383–1390.
J Soc Cosmet Chem, 1:311–326. 22. Levius HP, Drommond FG. (1953). Elevated temperature as an
 2. Griffin WC. (1954). Calculation of HLB values of non-ionic artificial breakdown stress in the evaluation of emulsion stability. J
For personal use only.

surfactants. J Soc Cosmet Chem, 5:249–256. Pharm Pharmacol, 5:743–756.


  3. Pasquali RC, Taurozzi MP, Bregni C. (2008). Some considerations 23. Emulsion and HLB System. Convergent Cosmetics [online] 2007
about the hydrophilic-lipophilic balance system. Int J Pharm, Available at: http://www.lotioncrafter.com/pdf/Emulsions_&_
356:44–51. HLB_System.pdf. Assessed on 12 November 2011.
  4. Couteau C, Deme A, Cheignon C, Coiffard LJM. (2012). Influence 24. Gupta A, Myrdal PB. (2004). Development of a perillyl alcohol
of the hydrophilic-lipophilic balance of sunscreen emulsions on topical cream formulation. Int J Pharm, 269:373–383.
their water resistance property. Drug Dev Ind Pharm [online];0:1–3. 25. Margaret MR, Andrew DW, Peter JW. (2002). Emulsions creaming
Available at: http://informahealthcare.com/doi/abs/10.3109/036 and rheology. Curr Opin Colloid Interface Sci, 7:419–425.
39045.2011.653362. Accessed on 21 April 2012. 26. Pal R. (2011). Rheology of simple and multiple emulsions. Curr
 5. Nielloud F, Marti-mestres G, Laget JP, Fernandez C, Maillols Opin Colloid Interface Sci, 16:41–60.
H. (1996). Emulsion formulations: study of the influence of 27. Gullapalli RP, Sheth BB. (1999). Influence of an optimized non-
parameters with experimental designs. Drug Dev Ind Pharm, ionic emulsifier blend on properties of oil-in-water emulsions. Eur
22:159–166. J Pharm Biopharm, 48:233–238.
  6. Orafidiya LO, Oladimeji FA. (2002). Determination of the required 28. Bechner P. (1965). Emulsion theory and practice. London:
HLB values of some essential oils. Int J Pharm, 237:241–249. Chapman & Hall; 152–153.
 7. Rieger MM. (1987). Emulsion. In: Lachman L, Lieberman HA, 29. Hamed M, Chin PT, Nazimah SAH, Salmah Y. (2008). Optimization
Kanig JL, ed. The Theory and Practice of Industrial Pharmacy. of the contents of Arabic gum, xanthan gum and orange oil affecting
Bombay: Varghese Publishing House, 502–533. turbidity, average particle size, polydispersity index and density in
  8. Thorsell W, Mikiver A, Malander I, Tunon H. (1998). Efficacy of orange beverage emulsion. Food Hydrocolloid, 22:1212–1223.
plant extracts and oils as mosquito repellents. Phytomedicine, 30. Brookfield. CT3 Texture Analyzer Operating Instructions. Manual
5:311–323. No. M/08-371A0708, Brookfield Engineering Laboratories, Inc. USA.
  9. Ansari MA, Razdan RK. (1995). Relative efficacy of various oils in 31. Brookfield Texture Pro CT3 Application Software Operating Instructions
repelling mosquitoes. Indian J Malariol, 32:104–111. Manual No. M08-373. Brookfield Engineering Laboratories, Inc. USA.
10. Data requirements for registration of biopesticides in OECD 32. Aime DB, Arntfield SD, Malcolmson LJ, Ryland D. (2001). Textural
member countries: survey results, OECD Environment Monograph analysis of fat reduced vanilla ice cream products. Food Res Int,
[online] 1996;106:72–73. Available at: http://www.oecd.org/ 34:237–246.
officialdocuments/publicdisplaydocumentpdf/?cote=OCDE/ 33. Contreras MD, Sanchez R. (2002). Application of a factorial design
GD(96)13&docLanguage=En. Accessed on 28 April 2012. to the study of the flow behavior, spreadability and transparency of
11. Proposed Rules Federal Resister US FDA [online] 2007;72:7941– a Carbopol ETD 2020 gel. Part II. Int J Pharm, 234:149–157.
7945. Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/ 34. Riel RR. (1960). Specifications for the spreadability of butter. J
E7-2890.pdf. Accessed on 25 April 2012. Dairy Sci, 43:1224–1230.
12. Sweetman SC. (2005). Dose adjustment in renal impairment:
35. Mahalik NP, Nambia AN. (2010). Trends in food packaging and
response from Martindale: the Complete Drug Reference. BMJ, manufacturing systems and technology. Trends Food Sci Tech,
331:292–293. 21:117–128.

 Drug Development and Industrial Pharmacy

You might also like