Evaluation of Novel Cooling Gel Sheets for Antipyretic Effect

Abstract

Rationale: Fever is basically rise in body temperature above normal. Fever itself is not a disease but it is an indication that the body is trying to fight an illness or an infection. Fever is usually associated with physical discomfort, and most people feel better when the fever is treated. But depending on age, physical condition, and the underlying cause, the patient may or may not require medical treatment for the fever alone. In some cases it is not recommended to treat fever as the rise in temperature is important to kill the viruses and bacteria. These are the causes of the infection but rise in the temperature heats up the body and causes discomfort. There are various approaches to cool the body from the outside without treating the cause of the fever. They include lukewarm or cool wraps or baths, cold drinks and very light clothing. Using a wet cloth on the forehead is an age old remedy for treating fever but the problem with this method is that the cloth needs to be changed after every 1 or 2 minute. Methods: The formulations were evaluated for Clinical trials of the patches. Conclusion: From the present investigation it can be concluded that that C5 formulation showed optimum homogeneity, consistency, viscosity, swelling studies and stability. Cooling gel sheets could be a potential method for reducing fever in near future which can be replacements for the old method of applying wet cloth on the forehead. The cooling gel sheets could provide cooling for maximum 6-8 hrs with a single sheet.

Full text

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International Journal of Current Pharmaceutical Review and Research; 9(1); 12-15
ISSN: 0976 822X
Research Article
Author for Correspondence: shahasma09@gmail.com
Evaluation of Novel Cooling Gel Sheets for Antipyretic Effect
Farooq S A*1, Saini V1, Singh R1, Ahmad S2.
1M.M College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana.133207.
2Unijules Life Sciences Ltd, B# 35 & 36 MIDC Industrial Area, Kalmeshwar, Nagpur-441501, India.
Received: 7th Dec, 17; Revised: 27th Jan, 18, Accepted: 4th Feb, 18; Available Online: 25th Feb, 2018
ABSTRACT
Rationale: Fever is basically rise in body temperature above normal. Fever itself is not a disease but it is an indication
that the body is trying to fight an illness or an infection. Fever is usually associated with physical discomfort, and most people
feel better when the fever is treated. But depending on age, physical condition, and the underlying cause, the patient may or may
not require medical treatment for the fever alone. In some cases it is not recommended to treat fever as the rise in temperature is
important to kill the viruses and bacteria. These are the causes of the infection but rise in the temperature heats up the body and
causes discomfort. There are various approaches to cool the body from the outside without treating the cause of
the fever. They include lukewarm or cool wraps or baths, cold drinks and very light clothing. Using a wet cloth on the
forehead is an age old remedy for treating fever but the problem with this method is that the cloth needs to be changed after
every 1 or 2 minute. Methods: The formulations were evaluated for Clinical trials of the patches. Conclusion: From the
present investigation it can be concluded that that C5 formulation showed optimum homogeneity, consistency, viscosity,
swelling studies and stability. Cooling gel sheets could be a potential method for reducing fever in near future which can
be replacements for the old method of applying wet cloth on the forehead. The cooling gel sheets could provide cooling
for maximum 6-8 hrs with a single sheet.
Keywords: Aquagel, Fever, Cooling gel Sheet, Hydrogel, Temperature
INTRODUCTION
Hydrogels are highly absorbent natural or synthetic
polymers which can contain over 99.9% water. The
polymer chains contain acidic or basic groups bound to
them1. The acidic groups on the chains deprotonate at high
pH, whereas the basic groups protonate at low pH. In the
presence of an aqueous solution, the polymer chains
absorb water and the association, dissociation and binding
of various ions to polymer chains causes the hydrogel to
swell2. As the temperature raises the heat of the skin causes
the evaporation of water contained within cooling gel sheet
which creates a cooling sensation on the surface of the
skin.
MATERIALS AND METHODS
HPMC (1 lakh cps), Carbopol 934 NF, Xanthum gum,
Sodium CMC, Guar gum, Gelatin, Sodium polyacrylate,
HPC (Hydroxyl propyl cellulose), Methacrylic acid,
Ultraze 20, Polyvinyl alcohol, Polyethylene glycol 400,
Dimethicone were obtained from Unijules Life Sciences,
Nagpur. All the ingredients were of analytical grade.
Different formulations were formulated using different
polymers like Xanthan gum, HPMC, sodium CMC, Guar
gum, Gelatin. Amongst all HPMC forms the most stable
gel. The gels made from other polymers were not stable.
The viscosity of the gels was low and had less water
absorbing capacity as compared to HPMC.
Clinical Trails
Aim of the study
To determine safety and efficacy of cooling gel sheets in
the patients of mild to moderate pyrexia.
Study design
This was an open label, phase 2 clinical trial conducted at
the outpatient department of SHRI BRAMHACHAITANYA
AYURVEDIYA & PANCHAKARMA HOSPITAL, KARAD,
Maharashtra, India. Patients of either sex aged between 0
to 50 years of age were selected for the study. Patients were
evaluated by proper inclusion and exclusion criteria and
who were willing to give informed consent. They were
evaluated for pyrexia of primary origin. Follow up was
taken after every hour up to the 8 hours. In each visit
patients were assessed for symptoms score.
Materials and methods
Proper Inclusion and Exclusion criteria were decided as:
Inclusion criteria: A total of 57 patients of either sex,
between 0-50 years of age were taken in which the
diagnosis of pyrexia of primary origin (viral fever,
infectious fever) was confirmed.
Exclusion criteria: Patients with fever higher than 103 oC
and with acute complications were excluded from the trial.
Pregnant and lactating women, patients with concomitant
severe illness necessitating other medications, patients
with severe hypertension, history of severe unstable
angina, myocardial infarction, CVAs, renal failure, and
those patients, who were not willing to give informed
consent were also excluded from the study.

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IJCPR, Volume 9, Issue 1, January - February 2018 Page 13
Dose & duration of treatment
Adult: This gel sheet can be applied externally as and when
required, this can be applied every 4 hours or every 6 hours
as per the intensity of the fever
Children: 6 hourly
No other analgesic, antipyretic was given until the
patient’s symptoms were seen during the course of
therapy.
Study procedure
All eligible patients were given cooling gel sheet for
application on forehead every 6 hours.
All the patients were assessed for body temperature before
the start of the treatment and after every 1 hour they were
being assessed for body temperature. The improvement in
the pyrexia was assessed using a predefined symptom
score scale from 0 to 3 (0=absent, 1=mild, 2=moderate and
3=severe).
Primary and secondary efficacy parameters
Table 1: Report Synopsis
Name of the Sponsor
UNIJULES LIFE SCIENCES LTD, NAGPUR
Name of the Finished Products Test Products :
“COOLING GEL SHEETS”
BATCH NO. :
177E001
Name of the Active Ingredients :
Sr.
no.
Ingredients
wt. in gram
(1)
Acrypol 934
0.4 g
(2)
HPMC (1lakh cps)
4 g
(3)
Water
100ml
(4)
Poly vinyl Alcohol
0.5 g
(5)
Polyethylene glycol 400
1.5 g
(6)
Dimethicone
2 g
(7)
Menthol(1%)
2 ml
Title of the study :
“AN OPEN LABLE STUDY TO EVALUATE SAFETY
AND EFFICACY OF COOLING GEL SHEETS IN THE
PATIENTS OF PYREXIA”
Clinical Investigator :
Dr. S. B. Malekar
SHRI BRAMHACHAITANYA AYURVEDIYA &
PANCHAKARMA HOSPITAL, KARAD.
Study Centre
Out Patients Department
SHRI BRAMHACHAITANYA AYURVEDIYA &
PANCHAKARMA HOSPITAL, KARAD.
Objectives
To study the safety & efficacy of “COOLING GEL
SHEETS” in pyrexia patients.
Number of subjects
57
Diagnosis & Criteria for inclusion
Pyrexia between 99 oC to 103 oC
Route of administration
Local
Table 2: Observations of the clinical trails
Column Title
0 hr
(A)
1 hr
(B)
2 hr
(C)
4 hr
(D)
6 hr
(E)
8 hr
(F)
Mean
2.589285
1.410714
0.660714
0.375
0.150943
0.132075
Standard deviation
(SD)
0.4964
0.6260
0.8587
0.7523
0.5334
0.5203
Sample size
56
56
56
56
53
53
Std. error of mean
(SEM)
0.06634
0.08365
0.1147
0.1005
0.07326
0.07146
Lower 95% Conf.
limit
2.456
1.243
0.4306
0.1734
0.003803
0.2756
Upper 95% Conf.
limit
2.722
1.578
0.8908
0.5766
0.2981
0.2756
Minimum
2.000
1.000
0.000
0.000
0.000
0.000
Median
(50th percentile)
3.000
1.000
0.000
0.000
0.000
0.000
Maximum
3.000
3.000
3.000
3.000
3.000
3.000
Normality test KS
0.3852
0.4048
0.3149
0.4409
0.5171
0.5247
Normality test P
value
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
Passed normality
test?
No
No
No
No
No
No

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Primary efficacy parameters were considered as reduction
in for body temperature and symptom score assessment.
Secondary efficacy parameters were reduction in the
incidence of adverse events and overall compliance to the
therapy.
Statistical analysis
Statistical analysis was done on the basis of intent to treat,
to compare the body temperature before and after every
assessment. The minimum level of significance was fixed
at 95% confidence limit and a 1-sided p value of <0.05 was
considered as significant.
RESULTS AND DISCUSSION
Clinical Trails
About 73 patients were screened for trial out of them 57
patients gave complete follow up.
There was significant difference observed in mean body
temperature level from 2.589+/-0.496 to 0.132+/-0.520
One-way Analysis of Variance (ANOVA)
The P value is < 0.0001, considered extremely significant.
Variation among column is significantly greater than
expected by chance.
Tukey-Kramer Multiple Comparisons Test
If the value of q is greater than 4.061 then the P value is
less than 0.05.
No adverse events were noted during the treatment as there
were no significant changes observed in other symptoms.
The clinical trial of cooling gel sheets observed a
significant difference in the body temperature and pyrexia
pattern. The patch contains menthol, which reinforces the
analgesic feeling of coldness, helping to relax tense
muscles in the head and neck. For instant cooling, calming
relief, use with or without oral medication, whenever
headache or migraine pain strike. The patch contains a high
percentage of water which works with the body’s natural
cooling system helping to cool the body. As the
temperature rises, the heat of the skin causes the
evaporation of water contained within cooling gel sheet
Table 3: Comparison table of the columns
Comparison
Mean Difference
q
P value
Column A vs Column B
1.179
13.630
*** P<0.001
Column A vs Column C
1.929
22.304
*** P<0.001
Column A vs Column D
2.214
25.609
*** P<0.001
Column A vs Column E
2.438
27.809
*** P<0.001
Column A vs Column F
2.457
28.024
*** P<0.001
Column B vs Column C
0.7500
8.674
*** P<0.001
Column B vs Column D
1.036
11.978
*** P<0.001
Column B vs Column E
1.260
14.368
*** P<0.001
Column B vs Column F
1.279
14.583
*** P<0.001
Column C vs Column D
0.2857
3.304
ns P>0.05
Column C vs Column E
0.5098
5.814
*** P<0.001
Column C vs Column F
0.5286
6.029
*** P<0.001
Column D vs Column E
0.2241
2.555
ns P>0.05
Column D vs Column F
0.2429
2.771
ns P>0.05
Column E vs Column F
0.01887
0.2123
ns P>0.05
Figure 1: Improvement in the body temperature.
0
0.5
1
1.5
2
2.5
3
0hr 1 hr 2 hr 4 hr 6 hr 8 hr
Mean
Hours

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which creates a cooling sensation on the surface of the
skin. The excellent heat transfer ability is made possible by
the gels unique structure which disperses heat freely and
maintains a constant and steady cooling effect that lasts up
to 8 hours. TDDS is a drug delivery system in which skin
is used as the port of drug administration to provide
continuous transdermal drug infusion into the systemic
circulation. This system of drug administration has many
advantages .it bypass hepatic first pass metabolism. It
maintains a constant and prolonged drug level in the body.
It avoids the risk and inconvenience of i.v therapy. It does
not necessitate hospitalization and close medical
supervision of administration. It avoids gastrointestinal
drug absorption difficulties caused by gastrointestinal pH,
enzymatic activity, and drug interactions with food, drinks,
or other orally administered drugs. It substitutes for oral
administration of medication when that route is unsuitable,
as in instances of vomiting and/or diarrhoea. It provides
capacity to terminate drug effect rapidly (if clinically
desired) by removal of drug application from the surface
of the skin.
Failure of oral antipyretics and increasing incidences of
adverse drug reactions to those drugs like acetaminophen
and nimesulide etc. have caused major threat to subjects
receiving this therapy especially in children and long term
consumers. Liver disorders and other toxicity symptoms of
these antipyretics can be avoided by use of this
unconventional method i.e. TDDS. A patient of viral fever
or other PUO’s can be given this therapy easily rather than
antipyretics without causing any systemic effects or
adverse drug reactions. This study proves efficacy and
safety of cooling gel sheets it helps reducing pyrexia to a
significant level which can reduce the necessity of
consumption of antipyretics.
CONCLUSION
The formulation C5 contained the highest water content.
This formulation does not cause any redness or abrasion so
this formulation can be used as a replacement for the old
method of sponging in which the cloth has to be changed
after every 2 min. This patch provides cooling upto 6 hrs
without any cumbersome replacements. The clinical trial
of the gel sheet further showed that the gel sheet can be
used in the future to reduce the fever without side effects
and effectively.
ACKNOWLEDGMENT
Authors are thankful to Unijules Life Sciences Ltd, Nagpur
for providing chemicals and their motivation and co-
operation to carry out this research work.
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