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Formulation and Evaluation of Transdermal Topical

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Formulation and Evaluation of Transdermal Topical

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Ritika Prasad
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Kashyap et al Journal of Drug Delivery & Therapeutics.

2020; 10(2):20-25

Available online on 15.03.2020 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics


Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits
unrestricted non-commercial use, provided the original work is properly cited

Open Access Research Article

Formulation and Evaluation of Transdermal Topical Gel of Ibuprofen


Kashyap Ankita*, Das Asha , Ahmed Abdul Baquee
Girijananda Choudhury Institute of Pharmaceutical Science, Azara, Guwahati- 781017, Assam, India

ABSTRACT
The present research work is based on the formulation and evaluation of topical gel of Ibuprofen where Carbopol 940 is used as the polymer.
Gels were prepared by dispersing the polymers in a mixture of water and glycerol with methyl paraben as the preservative and the varying
amount of ibuprofen, being kept under magnetic stirring until the homogeneous dispersion was formed. The dispersion was then neutralized
and made viscous by the addition of triethanolamine. The Carbopol gels of Ibuprofen were found to be homogenous with good drug loading.
The pH of all the gel formulations was found within the neutral pH range which is compatible with skin. And the viscosity of the formulations
was found to be feasible for topical drug delivery. The drug content of the three formulations was found in the range of 87.56% to 90.45%
which shows efficient drug loading. Results of In vitro drug release study showed that F5 formulation has better diffusion of drug through egg
membrane and hence further permeation studies were carried out through rat epidermis. The compatibility study showed that the major peaks
in FTIR spectra of the pure drug were found to be intact in their physical mixture. Hence there is no interaction between dru g and Carbopol in
their physical mixture. Carbopol can be effectively used as the polymer for topical gel preparation. And F5 formulation containing 0.5 % w/w
Carbopol 940 may be effectively used as topical transdermal delivery for Ibuprofen.
Keywords: Ibuprofen, Transdermal Gel, Drug release, Compatibility study

Article Info: Received 11 Jan 2019; Review Completed 14 Feb 2020; Accepted 20 Feb 2020; Available online 15 March 2020
Cite this article as:
Kashyap A, Das A , Ahmed AB, Formulation and Evaluation of Transdermal Topical Gel of Ibuprofen, Journal of Drug
Delivery and Therapeutics. 2020; 10(2):20-25 http://dx.doi.org/10.22270/jddt.v10i2.3902

*Address for Correspondence:


Ankita Kashyap, Assistant Professor, Girijananda Choudhury Institute of Pharmaceutical Science, Azara, Guwahati-
781017, Assam, India

INTRODUCTION number of advantages over the conventional method of drug


administration like-enhanced efficacy, increased safety,
The dosage forms, whether a tablet, an injection or a patch, greater convenience, improved patient compliance. The
to deliver the right amount of medicine at the right time to various advantages of Transdermal Drug Delivery System are
the right target site becomes complicated if each medicine is – It avoids significant presystemic metabolism and therefore
to be delivered in an optimal and preferred manner to the the need for the daily requirement is low. It reduces inter
individual patient. The medication may not be absorbed if it and intrapatient variability. Drug levels can be maintained in
is released too slowly or too rapidly, or the patient may the systemic circulation within the therapeutic limit. The
suffer adverse effects and as because it’s desired effects may duration of drug action following a single administration of
not last as long as it needed. These limitations are being the drug can be extended and the frequency of dosing is
overcome by transdermal drug delivery systems as they reduced. It improves patient compliance and acceptability of
achieve several advantages over conventional dosage forms. the drug therapy. Drug input can be terminated simply by
Transdermal drug delivery is a route which can deliver removal of the patch.[1,2,3] Taking into account several
medicines via the skin portal to systemic circulation at a advantages associated with Transdermal drug delivery route,
predetermined rate and maintain clinically effective we have decided to utilize ‘Ibuprofen’, which is a non-
concentrations over a prolonged period of time. Transdermal steroidal anti-inflammatory drug (NSAID) used for pain
route of drug administration avoids discomfort associated relief, fever reduction, and against swelling.[4] Carbopol 940
with parental therapy and improves patient compliance. This is used as the polymer, which is ideal for applications such as
route of administration also eliminates the side effects that clear gels, hydroalcoholic gels, creams.[5,6]
are caused by the conventional drug forms and also provide
controlled release of drugs directly into the bloodstream
through the intact skin. Transdermal delivery can provide a

ISSN: 2250-1177 [20] CODEN (USA): JDDTAO


Kashyap et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):20-25

Objective received only after the proposed study was approved by the
Institute Animal Ethics committee bearing the number
The objective is to prepare transdermal topical gel of
GIPS/IAEC/BPH/2013/4.
Ibuprofen using Carbopol 940 which can be effectively used
for transdermal topical delivery. Preparation of standard curve:
MATERIALS AND METHODS 0.1mg of ibuprofen was weighed accurately and was
dissolved in 10 ml of ethanol and the volume was adjusted to
Materials 100 ml by pH 7.4 and various dilutions were made to obtain
Chemicals concentration 2-50 mcg/ml and the absorbance was
measured in the Ultra Violet (UV) Spectrophotometer at
Ibuprofen (Hi Media, Mumbai, India), Triethanolamine λmax 267 nm, and a standard curve was obtained by plotting
(Merck ,Mumbai, India), Methyl Paraben (Hi Media, Mumbai, concentration against the absorbance.[7]
India), Glycerol (Merck, Mumbai, India), Carbopol (Balaji
Drugs, India) were procured and used in the investigation.All Preparation of transdermal gel:
other reagents used were of analytical grade. Gels were prepared by dispersing the polymers (Carbopol
Animals 940) in a mixture of water and glycerol with methylparaben
as the preservative and the varying amount of ibuprofen,
Wistar albino rats (male) were used of 250-500 gm were being kept under magnetic stirring until the homogeneous
used which were supplied by animal house of Girijananda dispersion was formed. The dispersion was then neutralized
Chowdhury Institute of Pharmaceutical Science which were and made viscous by the addition of triethanolamine [8,9] as
kept under proper laboratory condition. The animals were shown in Table 1.

Table 1: Gel Formulation


Formulation Drug (mg) Carbopol 940 Methyl Paraben Glycerin (ml) Triethanolamine
Code (gm) (mg) (ml)
F1 10 1 200 1 0.1
F2 10 0.5 200 1 0.1
F3 10 0.75 200 1 0.1
F4 20 0.5 200 1 0.1
F5 50 0.5 200 1 0.1

Preparation of pH 7.4: Viscosity


2.38 gm of Disodium Hydrogen Phosphate, 0.19 gm of Brookfield (DV-E Viscometer) attached with spindle was
Potassium Dihydrogen Phosphate and 8 gm of Sodium used for determination of viscosity. Gels were filled in jar
Chloride were weighed accurately and it was diluted up to and spindle was lowered perpendicularly taking care that
1000 ml.[10] spindle does not touch the bottom of the jar. The spindle
number 63 was rotated in the gel at 20 rpm. At each speed,
Evaluation Of Transdermal Gel:
the corresponding dial reading was noted. The reverse
Determination of gel pH reading was also noted and average was taken for these two
readings. The viscosity of the gel was obtained by the
The pH of the three gel formulations was determined by multiplication of the dial readings with the factors given in
using digital pH meter after calibration with standard buffer the Brookfield viscometer catalogs. The spindle size used is
pH 4.0, and 9.0 by inserting the electrode system into the 64.[13]
gel.[11]
Drug content
Spreadability
1 gm of the prepared gel was weighed accurately and
One of the criteria for a gel to meet the ideal quantities is dissolved in 10 ml of ethanol and was then filtered.1ml of
that it should possess good spreadability. It is the term the filtrate was taken and was diluted up to 100 ml by pH 7.4
expressed to denote the extent of the area to which gel and was observed in the Ultra violet (UV)
readily spreads on application to the skin or affected part. spectrophotometer at 267 nm.[14,15,16]
The therapeutic efficacy of a formulation also depends upon
its spreading value. Spreadability is expressed in terms of In-vitro drug release/permeation study
time in seconds taken by two slides to slip off from the gel
The drug release/ permeation studies of the prepared gels
and placed in between the slides under the direction of were carried out in Keshary-Chien diffusion cell for studying
certain load. Lesser the time is taken for separation of two the drug release from the gels through an egg membrane. Gel
slides, better the spreadability. It is calculated by using the sample (0.5g) was placed on the membrane and the diffusion
formula: S = M. L / T Where M = weight tied to upper slide, L
studies were carried out at 37 ± 0.5°C using 250 ml of
= length of the glass slide, T = time taken to separate the phosphate buffer (pH 7.4) as the receptor medium. Five
slides.[12]
milliliters of each sample was withdrawn periodically at 15,
ISSN: 2250-1177 [21] CODEN (USA): JDDTAO
Kashyap et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):20-25

30, 60, 120 and 240 minutes. Each sample was replaced with Drug spreadability study:
equal volume of fresh receptor medium. Then the samples
The spreadability of the different gel formulations after 1
were analyzed by UV spectrophotometer at 267 nm for the
min. was determined and was compared with a standard gel
drug content by using phosphate buffer as blank.[17,18,19]
and noted in Table 3.
Compatibility study
Table 3: Spreadability of Gel Formulation
The Fourier- transform infrared spectroscopy (FTIR) spectra
of pure drug, Carbopol, and physical mixture of drug Formulation Spreadibility (mean±SD)
Carbopol (1:3) were taken and studied for any interaction F1 19.79
using FTIR, Bruker Alpha instrument.[20,21,22]
F2 22.5
RESULT AND DISCUSSION
F3 21.25
Standard calibration curve of Ibuprofen:
F4 22.29
The standard calibration curve of Ibuprofen was plotted in
phosphate buffer, pH 7.4. The scanning of standard solution F5 22.08
has resulted maximum absorption peak at the wavelength of
Nurofen (Boots Healthcare) 21
267 nm. It was observed that Beer-Lambert‘s law was
obeyed within the concentration range of 2.0 μg/ml to 50.0
μg/ml, in phosphate buffer, pH 7.4 as shown in Table 2 and
Fig. 1. Viscosity:
The viscosity of the gel formulations was found between
15900 to 23230 cps. The results are shown in Table 4.
Table 4: Viscosity of Gel Formulation (20 rpm)
Formulation Viscosity (mean±SD)
F1 20800±4336.828
F2 23230±4984.532
F3 27700±5981.081
F4 15900±2969.848
F5 20100±4984.532

Fig 1: Standard Curve of Ibuprofen Drug Content:


PH of Ibuprofen Gel: The drug content of the gel formulations was found in the
The pH of the gel formulations was found as 7.0 to 7.5 and a range of 87.56 to 90.45 % which shows efficient drug
comparison study was done with a standard gel as shown in loading. The results are shown in Table-5.
Table 2. Table 5: Drug Content of Different Formulation
Table 2: pH of Gel Formulation Formulation Drug Content (mean±SD)
Formulation pH (mean±SD) F1 87.56±1.11
F1 7.2±0.18 F2 89.67±0.85
F2 7.5±0.20 F3 88.44±1.02
F3 7.0±0.15 F4 90.45±0.94
F4 7.3±0.07 F5 89.12±0.85
F5 7.2±0.18
Nurofen (Boots Healthcare) 7.4±0.14 In-vitro drug release/permeation study:
In-vitro drug release of all the formulation through egg
membrane is shown in Fig-2.

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Kashyap et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):20-25

Fig 2: RELEASE PROFILE OF IBUPROFEN FROM GELS THROUGH EGG MEMBRANE Formulation F5 shows the highest release
across the egg membrane chosen for permeation across rat epidermis. The result of permeation of transdermal gel across rat
epidermis is shown in Fig 3.

Fig 3: Permeation Profile oF Ibuprofen from Transdermal Gel through Rat Epidermis
Drug compatibility study: (stretching) at 1707.22, aromatic C=C (stretching) at
1504.04, alkyl halide groups i.e. C=F (stretching) at 1454.85,
Fourier- transform infrared spectroscopy (FTIR) spectra of
1266.87, 1225.51, 1179.08, are retained in the physical
pure drug, carbopol 940 and 1:3 ratio of the physical mixture
mixture. Thus it indicates that the drug is compatible with
of drug- carbopol 940 is presented in Fig-7 to 9 respectively.
the polymer used in the formulations as shown in Fig.4, Fig.5,
All the major peaks such as of alkenes i.e. C-H (stretching) at
Fig.6.
2988.29, 2949.21, 2867.97, carbonyl group i.e. C=O

Fig-4: FTIR Spectra of Pure Drug (Ibuprofen)

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Kashyap et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):20-25

Fig-5: FTIR Spectra of Carbopol 940

Fig-6: FTIR Spectra of Ibuprofen:Carbopol 940

DISCUSSION their physical mixture. Hence there is no interaction


between drug and Carbopol in their physical mixture.
The Carbopol gels of Ibuprofen were found to be
homogenous with good drug loading. The pH of all the gel CONCLUSION
formulations was found within the neutral pH range which is
compatible with skin. And the viscosity of all formulations It can be concluded that Carbopol can be effectively used as
the polymer for topical gel preparation. And F5 formulation
was found to be feasible for topical drug delivery. The drug
content of the three formulations was found in the range of containing 0.5 % w/w Carbopol 940 may be effectively used
as topical transdermal delivery for Ibuprofen.
87.56 to 90.45% which shows efficient drug loading. Results
of in-vitro drug release study showed that F5 formulation ACKNOWLEDGMENT
has better diffusion of drug through egg membrane and
hence further permeation studies were carried out through I am sincerely thankful to Girijananda Choudhury Institute of
rat epidermis. The compatibility study showed that the Pharmaceutical Science, Guwahati for carrying out the study
major peaks in Fourier- transform infrared spectroscopy and also grateful to my colleagues for their helping hand
(FTIR) spectra of the pure drug were found to be intact in support and coordination.

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Kashyap et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):20-25

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