Lincy john et al. Int. Res. J. Pharm.

2013, 4 (10)
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
www.irjponline.com ISSN 2230 8407
Research Article

FORMULATION AND EVALUATION OF AMLODIPINE TRANSDERMAL PATCHES USING

ETHYL CELLULOSE
Lincy john*, Arun Kumar and Sandra Samuel
Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India
*Corresponding Author Email: [email protected]

Article Received on: 17/08/13 Revised on: 21/09/13 Approved for publication: 20/10/13

DOI: 10.7897/2230-8407.041019
IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com
All rights reserved.

ABSTRACT
The aim of our study was to design and evaluate Amlodipine transdermal patches using polymers such as ethyl cellulose. Matrix type transdermal patches
containing Amlodipine were prepared by solvent casting method by using polymers like ethylcellulose 1 %, 1.5 %, 2 % and 2.5 % and a total of eight
formulations were prepared. Plasticizers used were propylene glycol and dibutylpthalate. The transdermal patches were evaluated for their physicochemical
properties like folding endurance, thickness, percentage moisture loss, percentage moisture absorption, drug content and water vapour transmission rate. The
diffusion studies were performed by using franz diffusion cell. Formulation E6 (1.5 % Ethylcellulose with dibutylphthlate) as plasticizers showed a maximum
release of 99 % in 24 hours. Out of these eight formulations of EC, 1.5 % Ethylcellulose (E6) was optimized since they produced a sustained and a complete
release over a period of 24 hours. Thus the knowledge on the use of ethyl cellulose to control drug release in transdermal delivery systems might be applicable
to other transdermal drug delivery system as well.
Keywords: Transdermal, ethylcellulose, Amlodipine

INTRODUCTION an electronic balance (Shimadzu AX200), magnetic stirrer

Delivering medicine to the general circulation through the (REMI model Mumbai), a sonicator (Spectra Lab, model
skin is seen as a desirable alternative to taking it by mouth or UCB 40), a hot air oven (Labhosp) and a Franz diffusion cell
by oral route. Transdermal drug delivery is defined as (self fabrication) were used in this study.
delivering the drug through the skin at controlled rate to the
systemic circulation. The transdermal patches uses a polymer Methodology
membrane to control the rate at which the drug contained in Formulation of Transdermal Drug Delivery System
the reservoir within the patch can pass through the skin and TDDS was developed using solvent evaporation method. In
into the blood stream1. Today most of the drug are taken this polymer is dissolved in particular solvent and then the
orally but, they are found not to be as effective as desired, So specified quantity of drug as well as plasticizers were added
to improve such character TDDS was emerged. Currently and was air dried for 24 h in petridish with help of inverted
TDDS is one of the most promising methods for drug funnel for controlled evaporation5,6. A total of 8 formulations
application. Transdermal drug delivery provides a leading were made in as shown in Table 1.
edge over injectables and oral route by increasing patient
compliances and avoiding first pass metabolism respectively. Preparation of Amlodipine Patches
TDDS not only provides a controlled, constant administration Drug loaded matrix type transdermal films of Amlodipine
of drug, but also allows continuous input of drug with short were prepared by solvent evaporation method. The polymers
biological half life and eliminates pulsed entry into systemic like EC were dissolved in particular solvents with help of
circulation which often causes undesirable side effect2. magnetic stirrer followed by the addition of drug into the
Transdermal drug delivery provides a leading edge over polymeric solution and then the plasticizers were
injectables and oral route by increasing patient compliances incorporated with continuous stirring and the volume was
and avoiding first pass metabolism respectively. TDDS not made up. The resultant solution was casted onto the petridish
only provides a controlled, constant administration of drug, and an inverted funnel was placed. After 24 hours the films
but also provide short biological half life and eliminates were removed by using sharp knife by inserting along the
pulsed entry into systemic circulation which often causes edge of the films and stored for further studies7.
undesirable side effect3,4. The objective of this research work
was to develop a transdermal system which can produce a Evaluation of Transdermal Patches
constant and prolonged release of the drug, to evaluate the Physical Appearance
effect of ethyl cellulose on the fabrication of the patch and All the prepared patches were visually inspected for color,
drug release from the patch, to evaluate the effect of clarity, flexibility and smoothness8.
plasticizers on the physico-chemical properties of the patch
and on drug permeation across the membrane. Thickness Uniformity
The thickness of the formulated film was measured at 3
MATERIALS AND METHODS different points using a calliper and average thickness was
Material calculated9.
Amlodipine was kindly supplied as gift samples by Microlabs
Pharmaceuticals, Banglore, India. Polymers and plastizier Folding Endurance
used were purchased by SD fine chemicals, India. The Drug The folding endurance was measured manually for the
analysis was performed using UV Spectroscopy. In addition, prepared films. A strip of film 1 cm2 was cut and repeatedly

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 Lincy john et al. Int. Res. J. Pharm. 2013, 4 (10)
folded at the same place till it broke. The number of times the RESULT
film could be folded at the same place without breaking or Calculation of Total Drug Loading
cracking gives the value of folding endurance10. The formulation of the patch was made in such a way that
each small circular patch of 1.4 cm radius (which is the
Percentage Moisture Absorption radius of the franz diffusion cell) contains 5 mg of the drug.
The films were weighed accurately and placed in desiccators The total amount of drug to be loaded in the patch was
containing 100 ml of saturated solution of potassium chloride calculated by measuring the total area of the petri dish in
after 3 days; the films were taken out and weighed. The which the patch will be casted. The calculation was done as
percentage moisture absorption was calculated using the follows;
formula11.
Area of the small circular patch = 6.1544 cm2
% moisture absorption= Final weight Initial weight x100 Desired drug content in the small patch = 5 mg
Initial weight Area of the petri dish = 67.89 cm2
Total amount of drug to be loaded = 67.89 x 5 / 6.1544 = 55 mg
Hence 55 mg of the drug was added in each formulation in order to get 5 mg
per small circular patch
Percentage Moisture Loss
The films were weighed accurately and placed in a Preparation of Transdermal Patches
desiccators containing anhydrous calcium chloride15. After 3 As per the methodology transdermal patches using EC were
days, the films were taken out and weighed. The percentage prepared by using solvent casting method.
moisture loss was calculated using the formula given below12.
Evaluation of Prepared Transdermal Patches
% moisture loss= Initial weight Final weight x100
Initial weight Folding Endurance
In general, folding endurance of all the films was found to be
Water Vapor Transmission Rate satisfactory indicating good strength and elasticity. The
Glass vials of 5ml capacity were washed thoroughly and observed values are given in Table 2. Folding endurance of
dried to a constant weight in an oven. About 1 g of fused EC was found to be in the range of 70-80. Folding endurance
calcium chloride was taken in the vials and the polymer films was found to increase with the polymer content.
were fixed over the brim with the help of adhesive tape. Then
the vials were weighed and stored in a humidity chamber of Thickness
70 80 % RH condition for a period of 24 h. The vials were Thickness of EC were evaluated with the use of a vernier
removed and weighed after 24 h to note down the weight gain caliper and was found to be in the range of 0.20 - 0.25 mm.
and transmission rate was found out13.
Percentage Moisture Loss
Transmission rate= Final weight Initial weight x100 Percentage moisture loss for ethyl cellulose containing
Time x Area patches was found in the range of 2.12 13.68 %. Percentage
moisture loss of prepared ethyl cellulose patches was found
Drug Content to be increased with increase in the percentage of the polymer
1.1544 cm2 areas of the small films were cut and were (1 %, 1.5 %, 2 % and 2.5 %) irrespective of the plasticizers
dissolved in sufficient quantity of methanol. The volume was (DBP and PG) used.
made up to 100 ml. The absorbance of the diluted solution
was measured at 238 nm and the drug content in the film was Percentage Moisture Absorption
calculated14. Percentage moisture absorption for EC was found in the
range of 6.21 10.31 %. Percentage moisture absorption
In- vitro Drug Diffusion Studies tends to decrease with increase in the percentage of EC (1 %,
In- vitro diffusion studies were performed by using franz 1.5 %, 2 %, 2.5 %) irrespective of plasticizers (DBP and PG)
diffusion cell with a receptor compartment capacity of 20 ml. used.
The synthetic cellophane membrane was mounted between
donor and receptor compartment of the diffusion cell. The Water Vapour Transmission Rate
formulated patches were cut into size of 1.4 cm radius and Water vapour transmission rates for EC was found in the
placed over the drug release membrane and the receptor range of 0.189 0.243 g/cm2/h. Water vapour transmission
compartment of the diffusion cell was filled with phosphate rate results were found to be similar to the results obtained in
buffer pH 7.4. The whole assembly was fixed on a magnetic moisture absorption studies.
stirrer, and the solution in the receptor compartment was
constantly and continuously stirred using magnetic beads at Drug Content
50 rpm. The sample of 2 ml were withdrawn at time intervals Drug content in each small circular patches were analyzed
of 30 minutes, 1 h, 1.30 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h and spectrophotmetrically and It was observed that all the
24 h and analyzed for drug content spectrophotomerically at formulations showed a satisfactory drug content values
238 nm15. ranging from 92 99 %.
Table 1: Formulations Containing EC Patches

Drug Polymers Plasticizers Polymer Percentage (%)

Amlodipine Ethyl DBP 1
cellulose PG 1.5
2
2.5
EC = Ethylcellulose ; PG = Propyleneglycol ; DBP = Dibutylphthlate

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 Lincy john et al. Int. Res. J. Pharm. 2013, 4 (10)
Table 2: Evaluation of Prepared EC Patches

Formulations Folding Thickness Percentage Moisture Percentage Moisture Water Vapor Transmission
Endurance (mm) loss (%) Absorption (%) Rate (g/cm2/h)
E 1 (1 % EC and PG) 72 0.21 2.12 9.31 0.2439
E 2 (1.5 % EC and PG) 74 0.22 8.69 6.54 0.2345
E 3 (2 % EC and PG) 75 0.23 11.36 6.59 0.2168
E 4 (2.5 % EC and PG) 76 0.24 11.62 5.71 0.2019
E 5 (1 % EC and DBP) 75 0.22 2.52 10.31 0.2303
E 6 (1.5 % EC and DBP) 77 0.23 5.25 8.52 0.2205
E 7 (2 % EC and DBP) 79 0.24 6.48 7.65 0.2032
E 8 (2.5 % EC and DBP) 80 0.25 13.68 6.81 0.1897
EC = Ethylcellulose ; PG = Propyleneglycol ; DBP = Dibutylphthlate

Table 3: Assay and Cumulative drug release of Prepared EC Patches

Formulation Assay (%) Cumulative drug release at 8 h (%) Cumulative drug release at 24 h (%)
E 1 (1 % EC and PG) 98.98 82.34 -
E 2 (1.5 % EC and PG) 98.41 61.38 92.80
E 3 (2 % EC and PG) 96.74 51.62 74.30
E 4 (2.5 % EC and PG) 97.97 32.14 65.98
E 5 (1 % EC and DBP) 92.29 85.21 -
E 6 (1.5 % EC and DBP) 95.95 58.23 99.12
E 7 (2 % EC and DBP) 96.39 56.24 76.80
E 8 (2.5 % EC and DBP) 97.97 40.12 69.39
EC = Ethylcellulose ; PG = Propyleneglycol ; DBP = Dibutylphthlate

Figure 1: Diffusion study of E1, E2, E3 and E4

Figure 2: Diffusion study of E5, E6, E7 and E8

Diffusion Study release respectively for PG and DBP containing patches at

Effect of EC Patches on Drug Release the end of 24 hours. When concentration of EC was further
As shown in Table 3, the formulations with 1 % EC with PG increased to 2 % and 2.5 %, the formulations showed the
and DBP (E1 and E5) as plasticizers showed a maximum least percentage drug diffusion of just 30 40 % at 8 hours
release of more than 80 % within 8 hours. The formulation and around 65 75 % at the end of 24 hours. From the above
with 1.5 % EC (E2 and E6) showed around a 61.38 % and result it was observed that 1.5 % EC containing formulations
58.23 % release at 8 hours and about 92.8 % and 99.12 %

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 Lincy john et al. Int. Res. J. Pharm. 2013, 4 (10)
produced a sustained and complete release over a period of recent years. The transdermal system offers several
24 hours. advantages over oral dosage forms which include avoidance
of hepatic first pass effect metabolism, decrease in frequency
DISCUSSION of administration, providing steady state plasma
The present study was aimed at preparing transdermal concentration and improves patient compliance etc. Hence in
patches containing Amlodipine for sustained release of drug this study an attempt was made to deliver Amlodipine
and studies the effect of polymer on rate of release. Since the transdermally in order to provide a constant serum level of
oral bioavailability of Amlodipine is poor due to first pass drug over the prolonged period of time. Polymers like EC
metabolism, different matrix type transdermal patches were were selected for the study and were used at different
formulated. Transdermal patches composed of different concentrations. PG and DBP were incorporated as
polymers such EC at different concentration of 1 %, 1.5 %, 2 plasticizers in the formulations. On evaluation of various
% and 2.5 % using two different plasticizers PG, DBP were parameters it was found that the polymers produced
prepared using solvent casting technique. A total of 8 satisfactory results with respect to the physical characteristics
formulations were made using Ethyl cellulose. The of the film and the release characteristics across synthetic
formulated patches were subjected to physicochemical membrane. The release profile suggested that increase in
evaluatory parameters i.e. folding endurance, thickness, polymer content led to decrease in release rate of the drug.
moisture loss, moisture absorption, water vapour Lower concentration of polymers gave an initial burst release
transmission rate and assay to ascertain their integrity and of about 50 % within 2 hours and as concentration were
physical stability. Folding endurance value of matrix films increased they were able to sustained the release for
were found within 230 310 no of folds, indicating good prolonged period but could not release the entire content in
strength and elasticity and that the patch would maintain the the prescribed time limit. Hence it was concluded that
integrity with general skin folding when applied. The concentration of 1.5 % for EC with DBP (E6) as plasticizers
thickness of all the formulations indicates physical will be the most suitable one for the transdermal systems of
uniformity among the prepared patches. The drug content Amlodipine as it showed sustained and complete release at a
analysis values show minimum batch variability. Hydrophilic period of 24 hours. Further studies using various animal
polymers like HPMC and CS with increased concentration models can throw more light on the variability of the
showed an increase in water vapor transmission rate and % prepared transdermal systems.
moisture absorption as it was able to retain water in the patch
while hydrophobic polymer like EC with increased ACKNOWLEDGEMENT
concentration showed a decrease value, as it was able to repel The authors are thankful to the staff and management of kovai medical
college, Coimbatore, India for providing all the facilities to accomplish my
water. Optimization of the formulated patches was done by research work.
performing in-vitro diffusion rate studies using franz
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Source of support: Nil, Conflict of interest: None Declared

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