FORMULATION AND EVALUATION OF TRANSDERMAL PATCH OF AN

Vol - 4, Issue - 1, Jan 2013 ISSN: 0976-7908 Ghinaiya et al

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PHARMA SCIENCE MONITOR

AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

FORMULATION AND EVALUATION OF TRANSDERMAL PATCH OF AN

ANTIHYPERTENSIVE DRUG

Mitali Ghinaiya*

N. R. Vekaria Institute of Pharmacy, C.L. College Campus, Bilkha road, Junagadh-362001, Gujarat, India

ABSTRACT Valsartan is a new potent, highly selective and orally active antihypertensive drug because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make valsartan a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS) of valsartan and to determine the effect of plasticizers and different polymeric grades of hydroxy propyl methyl cellulose (K4M, K15M, K100M) on drug release. The matrix type TDDS of valsartan were prepared by solvent casting technique. Six formulations were composed of hydrophilic polymers like sodium alginate and different polymeric grades of hydroxy propyl methyl cellulose (K4M, K15M, and K100M) and different plasticizers like PEG-400 and PG. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro drug release, ex-vivo permeation and skin irritation study. The ex-vivo permeation study was carried out using rat skin for optimized formulation. All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 12 hrs from the six formulations were 92.45 %, 76.95 %, 65.43 %, 99.8 %, 96.48 % and 89.4 % respectively. Ex-vivo drug release values for the cumulative amount of the drug permeated across the rat skin from optimized formulation was 95.95 %. By fitting the data into zero order, first order, Higuchi model and Korsemeyer peppas, it was concluded that drug release from matrix films followed zero order release model and the mechanism of the drug release was due to swelling of hydrophilic polymers. The patches were seemingly free of potentially hazardous skin irritation. In conclusion, the present data confirm the feasibility of developing TDDS of valsartan for potential therapeutic use. Keywords: Transdermal drug delivery, Valsartan, Hydrophilic polymers.

INTRODUCTION

Currently, transdermal drug delivery is one of the most promising methods for drug

application. Increasing numbers of drugs are being added to the list of therapeutic agents



that can be delivered to the systemic circulation via skin. The transdermal route offers

several advantages over conventional dosage forms such as tablets and injections,

including avoidance of first-pass metabolism by the liver, minimization of pain, reduction

of side effects, extended duration of activity, reduction in the fluctuations of drug

concentrations in the blood, and possible sustained drug release1.

Valsartan is a non peptide, orally active and specific angiotensin II antagonist acting on

the AT1 receptor subtype. The Valsartan heart failure trial demonstrated that the use of

Valsartan was associated with reduced rate of heart failure related hospitalizations and

mortality as well as shorter duration of hospitalization2. Valsartan, N- valeryl- N[[2- (1H-

tetrazol- 5- yl)biphenyl- 4- yl] methyl] valine has an empirical formula of C24H29N5O3

and a molecular weight of 435.5 g/mol3,4,5. It was synthesized in 10 steps and patented in

19903.Valsartan is available as a white, microcrystalline powder. Valsartan is considered

as a class II compound, i.e. water-insoluble and highly permeable6. Valsartan is poorly

soluble and aqueous solubility is reported to be less than 1 mg/ml. The drug is rapidly

absorbed following oral administration, with a bioavailability of about 23%. Peak plasma

concentrations of Valsartan occur 2 to 4 h after an oral dose and 94% to 97% of the drug

is bound to plasma proteins5.

The aim of the study is to achieve the objective of systemic medication through topical

application and release of drug via skin by developing transdermal drug delivery system.

To obtain a controlled, predictable and reproducible absorption and release in to blood

stream, more uniform plasma levels, improved bioavailability, reduced side effects,

painless and simple application are some of the potential need to formulate the

transdermal drug delivery system arises.

MATERIALS AND METHODS

Materials

Valsartan was received as gift sample from Torrent research centre, Ahmedabad, India.

Na alginate, Hydroxy propyl methyl cellulose (K4M, K15M and K100M), Polyethylene



glycol 400 and Propylene glycol were received from Yarrow chem. Ltd, Mumbai. All the

other solvents and chemicals were of Laboratory Reagent grade.

Determination of solubility of Valsartan7, 8

The Valsartan has very low aqueous solubility. The solubility was determined in distilled

water and phosphate buffer pH 7.4. Here, excess drug (50 mg) was added to 50 ml

distilled water/ phosphate buffer pH 7.4 in a 50 ml volumetric flask and the mixture was

shaken and kept for 48 h at room temperature. The sampling was done on 24th & 48th

hour and filtered immediately using a whatman filter paper. The filtered sample was

diluted suitably and assayed at 250 nm for valsartan. The solubility experiments were

replicated for three times (n=3).

Determination of partition coefficient8, 9

The partition coefficient study was performed using n-octanol as the oil phase and

phosphate buffer pH 7.4 as the aqueous phase. The two phases were mixed in equal

quantities by adding 20 mg of drug in a separating funnel and were saturated with each

other at room temperature for 24 hrs. The saturated phases were separated by

centrifugation. The two phases were separated and were then analyzed for respective

drug contents. The partition coefficient of drug (Ko/w) was calculated using the

following formula:

Preparation of Transdermal Patches:

The valsartan patches were formulated using solvent casting method, by dissolving

weighed quantity of drug in required volume of methanol in a beaker. The selected

concentrations of polymers were dissolved in 10 ml of distilled water in another beaker.

To this beaker, add the methanol solution containing drug. Keep the beaker on



thermostatically controlled magnetic stirrer which is maintained at 37±0.5ºC. The

required quantity of plasticizer is added drop wise to the beaker while stirring is

continued until the drug is dispersed with polymer. The solution was poured into

petridish; an inverted funnel was placed over the petridish to prevent fast evaporation of

the solvent and the films were allowed to dry overnight at room temperature. Then the

Patches were cut into 2×2 cm2 and packed in an aluminum foil and stored in desiccators

for further use.

Table 1: Formulation table of Valsartan Patches

Ingredients F1 F2 F3 F4 F5 F6

Valsartan (mg) 195 195 195 195 195 195

HPMC K4M (mg) 200 - - 200 - -

HPMC K15M (mg) - 200 - - 200 -

HPMC K100M (mg) - - 200 - - 200

Na alginate (mg) 200 200 200 200 200 200

PEG-400 (%) 30 30 30 - - -

PG (%) - - - 30 30 30

Methanol (ml) 5 5 5 5 5 5

Water(ml) 10 10 10 10 10 10

Note: Each patch (2×2 cm2) contained 20 mg of Valsartan.

PEG-400 and PG (30% w/w of total dry polymer), incorporated as

plasticizers.

EVALUATION OF TRANSDERMAL PATCHES

1. Physical appearance10

All the prepared patches were visually inspected for color, clarity, flexibility and

smoothness.

2. Patch thickness11



The thickness of the patch was measured at three different points using an aerospace

micrometer

and average thickness was found out.

3. Weight uniformity10

For each formulation, the patches were cut from different positions and were weighed

individually and the average weight was calculated.

4. Folding endurance12

Folding endurance of patches was determined by repeatedly folding a small strip of film

(2 cm x 2 cm) at the same place till it broke. The number of times, the patch could be

folded at the same place without breaking gave the value of folding endurance.

5. Moisture content13

The patches were weighed and kept in a desiccator containing calcium chloride at room

temperature for 24 hr. The final weight of patch was noted. The percentage of moisture

content was calculated as a difference between initial and final weight with respect to

final weight.

6. Tensile strength14

Tensile strength of the patch was determined with JAMCO tensiometer (Mfg by PONCO

MACHINE TOOLS, Ahmedabad). The sensitivity of the machine was 1 g. It consisted of

two load cell grips. The lower one was fixed and upper one was movable. The test film of

size (2.5 × 1 cm2) was fixed between these cell grips and force was gradually applied till

the film broke. The tensile strength of the film was taken directly from the dial reading in

g. Tensile strength is expressed as follows:

7. Drug Content 15

2×2 cm2 area of the patches was cut and each dissolved in minor quantity of methanol,

till it dissolved. The volume was made up to 10 ml with phosphate buffer pH 7.4. 0.1 ml



was then withdrawn from this solution and diluted to 10 ml (dilution factor: 100). The

absorbance was measured at 250 nm. From the absorbance and the dilution factor, the

drug content in the patch was calculated. Average of triplicate readings was calculated.

8. In-vitro diffusion study10, 11, 13

In vitro diffusion study was performed by using a modified Franz diffusion cell with a

receptor compartment capacity of 200 ml. The dialysis membrane was mounted between

the donor and receptor compartment of the diffusion cell. The formulated patches were

cut into size of 2×2 cm2 and placed over the drug release membrane and the receptor

compartment of the diffusion cell was filled with phosphate buffer pH 7.4. The whole

assembly was fixed on a magnetic stirrer, and the solution in the receptor compartment

was constantly and continuously stirred using magnetic beads at 50 rpm; the temperature

was maintained at 37 ± 0.5˚C. The samples of 5 ml were withdrawn at time interval of 1

hr upto 12 hrs and analyzed for drug content spectrophotometrically at 250 nm against

blank. The receptor phase was replenished with an equal volume of phosphate buffer pH

7.4 at each time of sample withdrawal. The cumulative amounts of drug permeated were

plotted against time.

9. Ex-vivo skin permeation studies11

Preparation of rat skin

Male rats weighing 100-120 gm, free from any visible sign of disease were selected.

Using a depilatory preparation the hairs of the male rat was cutting by scissor. After

cleaning the skin with phosphate buffer pH 7.4, animal was sacrificed by excessive ether

inhalation. An incision was made on the flank of the animal and the skin was separated.

The prepared skin was washed with phosphate buffer pH 7.4 and used.

Ex-vivo skin permeation study

The prepared skin was tied on the donor compartment with transdermal patch. While

placing the patch, the donor compartment contains patch on stratum corneum side of skin

and dermis side was facing receptor compartment. Receptor compartment contains 200



ml of phosphate buffer pH 7.4 and every one hour 5 ml of sample was taken and replaced

the same with receptor fluid. After 12 hours sampling absorbance taken at 250 nm against

blank of phosphate buffer pH 7.4 by UV spectrophotometer.

10. Skin irritation study16

A primary skin irritation test was performed since skin is a vital organ through which

drug is transported. The test was carried out on healthy rabbits weighing 1.3 to 1.5 kg.

Drug free polymeric film of diameter 2×2 cm2 was used as control. The dorsal surface of

rabbits was cleared well and the hair was removed by using a depilatory preparation. The

skin was cleared with rectified spirit. The patches were applied to the shaved skin of

rabbits and secured using adhesive tape USP (Leucoplast TM). On one side of the back

control patch (without any drug) and on the other side an experimental patch were

secured. A 0.8%v/v aqueous solution of formaldehyde was applied as a standard irritant

and its effect was compared with test on same rabbit. The animals were observed for any

irritation for a period of 7 days. All the experimental protocols involving laboratory

animals were approved by the IAEC (Research Proposal No. : - NRV-04/2012)

11. Release kinetic models20

In order to understand the mechanism and kinetics of drug release, the drug release data

of the In- Vitro diffusion study were analyzed with various kinetic models like zero

order, first order, Higuchi’s, Peppa’s model and co-efficient correlation values were

calculated for the linear curves by regression analysis of the above plots.

12. Permeation Data Analysis17, 18

The flux (μg cm-2 hr-1) (Jss) of Valsartan was calculated from the slope of the plot of the

cumulative amount of Valsartan permeated per cm2 of skin at steady state against the

time using linear regression analysis:

Jss = (dq/dt)ss × 1/A

Where, (dq/dt)ss = steady state slope

A = effective diffusion area



The steady state permeability coefficient (Kp) of the drug through rat skin was calculated

by using the following equation:

Kp = Jss / C

Where, C = the concentration of Valsartan in the patch.

The penetration enhancing effect of penetration enhancer was calculated in terms of

enhancement ratio (ER), and was calculated by using the following equation:

13. Accelerated stability study16, 19

The optimized patch was subjected to stability study to evaluate any change in the

performance when exposed to accelerated conditions of environment during storage,

handling transport and use. The patch was packed in the aluminum foil and was kept in

stability chamber at 40˚C and 75% RH for a period of one month. The patch sample with

an area of 4 cm2 was cut and it was analyzed for physical parameters and drug content at

the end of a month. The average of triplicate readings was taken.

RESULTS AND DISCUSSION

The solubility of Valsartan was determined and found very less as 0.472 mg/ml in

distilled water and 0.995 mg/ml in phosphate buffer pH 7.4 after 48 hrs.

n-Octanol (oil phase) and phosphate buffer pH 7.4 (aqueous phase) were considered to be

the standard system to determine drug partition coefficient. The partition coefficient

value was found to be 0.0316±0.0004, which is nearer to the reported value (0.033).

The IR spectrum of Valsartan (Figure 5.3) sample revealed presence of major functional

groups. The characteristic functional groups of the pure valsartan and physical mixtures

of valsartan and polymers showed the peaks at the following wave number region: C-H

stretching (Alkane): 2970 cm-1

, C=O stretching: 1725 cm-1

; N-H bending (Aromatic

secondary amine): 1600 cm-1

, 1510 cm-1

; C-N stretching (Aromatic tertiary amine): 1200



cm-1

, 1100 cm-1

; Aliphatic tertiary amine: 1410 cm-1

; Disubstituted benzene: 750 cm-1

.

There was no appearance of any characteristics peaks. This shows that there was no

chemical interaction between the drug and the polymers used .The presence of peaks at

the expected range confirmed that the materials taken for the study are genuine and there

were no possible interactions occurred. Hence the sample is considered to be authentic.

The IR spectra showed no incompatibility between the polymer and Valsartan drug.

Figure 1: IR spectra of pure drug

Figure 2: IR spectra of Drug + HPMC K4M





Figure 5: IR spectra of Drug + Sodium alginate



Figure 6: IR spectra of mixture of drug and polymer

The formulated valsartan transdermal patches were evaluated for thickness, weight

uniformity, folding endurance, moisture content, tensile strength and drug content were

observed in Table 2.

All the prepared patches were observed physically and they were found to be transparent,

smooth, uniform and flexible. The thickness of the patches varied from 0.213 to 0.247

mm. Low standard deviation values in the patch thickness measurements ensured

uniformity of patches prepared by solvent casting technique. The weight uniformity was

to be in the range of 0.095 to 0.117 gm, which indicates that different batches patch

weights were relatively similar. The folding endurance was found to be in the range of

252 to 285. This data revealed that the patches did not break and had good mechanical

strength along with flexibility and maintained their integrity with general skin folding

when applied. The moisture content was found to be in the range 1.72 to 2.62%. The low

moisture content in the formulations resulted in stability of patches and not giving a

completely dried and brittle film. The tensile strength was found to be in the range of

94.27 to 112.60 g/cm2. The tensile strength measures the ability of a patch to withstand



rupture. The drug content was in the range of 97.08 to 99.17 %, which revealed that the

drug content was almost uniform in all the patches.

Table 2: Physico-chemical characterization of Valsartan transdermal patches

Formulation code

Patch thickness

(mm)

Weight uniformity

(gm)

Folding endurance

Moisture content

(%)

Tensile strength (g/cm2)

Drug content

(%) F1 0.213±0.012 0.095±0.0015 260±9.54 1.76±0.598 103.44±2.40 97.08±0.382 F2 0.230±0.01 0.104±0.0021 264±16.04 1.89±0.955 97.68±1.64 98.42±0.878 F3 0.243±0.006 0.113±0.002 252±4.04 2.62±0.845 94.27±0.78 98.25±1.25 F4 0.223±0.012 0.097±0.0015 267±7.55 1.72±0.606 112.60±1.20 97.92±0.382 F5 0.237±0.015 0.109±0.001 275±10.58 2.16±1.048 101.34±0.79 98.75±0.25 F6 0.247±0.006 0.117±0.0015 285±10.02 1.42±0.485 96.89±1.20 99.17±0.144

The in-vitro drug diffusion for six formulations is given in the Table 3. Here, F4

formulation showed maximum drug release.

Table 3: In-vitro drug release data of Valsartan Transdermal patches

Time (hrs)

% Cumulative drug release F1 F2 F3 F4 F5 F6

0 0 0 0 0 0 0 1 17.65±0.616 11.81±0.727 6.33±0.476 20.58±0.18 14.51±0.186 8.1±0.131 2 24.42±0.236 17.57±0.425 11.24±0.626 28.78±0.285 21.4±0.082 17.78±0.335 3 29.16±0.285 20.79±0.137 16.42±0.411 36.06±0.207 30.22±0.155 24.72±0.131 4 34.21±0.374 28.85±0.26 23.89±0.919 41.83±0.416 36.04±0.262 31.23±0.19 5 38.98±0.81 36.26±0.605 32.35±1.153 50.77±0.138 43.95±0.157 36.69±0.235 6 46.69±0.801 40.6±0.321 35.71±0.493 59.85±1.427 51.2±0.235 45.19±0.16 7 55.04±0.692 49.42±0.32 40.77±1.352 66.27±0.786 60.62±0.262 51.37±0.21 8 63.5±0.722 56.05±0.427 46.69±0.582 77.13±1.295 68.27±0.154 60.95±0.315 9 70.55±1.376 59.03±0.274 51.26±0.106 86.66±2.854 76.03±0.257 67.39±0.436

10 77.39±0.239 64.71±0.368 55.22±0.327 95.65±2.198 83.58±0.158 72.76±0.215 11 84.43±0.269 71.24±0.18 61.09±0.404 98.89±0.525 90.96±0.31 82.37±0.225 12 92.45±0.216 76.95±0.297 65.43±0.551 99.8±0.145 96.48±0.37 89.4±0.266



Figure 7: In-vitro drug release study of Valsartan Transdermal patches

The ex-vivo drug permeation study was carried out for optimized formulation using rat

skin as a semipermeable membrane and drug release data is given in the Table 4.

Table 4: Comparison of In-vitro and Ex-vivo drug release data of optimized batch

Time (hrs)

In-vitro % cumulative drug release

Ex-vivo % cumulative drug release

0 0 0 1 20.58 17.83 2 28.78 25.6 3 36.06 32.84 4 41.83 38.83 5 50.77 44.63 6 59.85 53.1 7 66.27 61.35 8 77.13 71.18 9 86.66 79.26 10 95.65 83.45 11 98.89 90.1 12 99.8 95.95



Figure 8: Comparison of In-vitro and Ex-vivo drug release data of optimized batch

A primary skin irritation test of patch F4 on rabbit was studied. No signs of erythema,

oedema or ulceration were observed on the skin of albino rabbits after 7 days.

To know the mechanism of drug release, the in-vitro release data were fitted to models

representing Zero‐order, First‐order, Higuchi and Korsemeyer‐Peppas model. It was

found that the release of Valsartan from the transdermal patch followed zero‐order

kinetics. The coefficient of determination (R2) was found to be much closer to 1 for zero

order equation. This suggests that the drug permeation from transdermal patches,

possibly owing to swelling of hydrophilic polymer. As per Korsemeyer-Peppas model,

Formulation F1, F2, F4 and F5 follows anomalous type drug release mechanism, i.e. non-

fickian diffusion. The release kinetic parameters are shown in Table 5.



Table 5: Kinetic release parameters for Valsartan transdermal patches

Formulation code

Kinetics Modeling Model

Zero order First order Higuchi Korsemeyer-Peppas

k0 R2 k1 R2 K R2 n R2

F1 7.139

0.990 -0.038 0.090 26.82 0.936 0.687 0.964 Anomalous

F2 6.207 0.994 -0.05 0.973 23.36 0.944 0.791 0.984 Anomalous

F3 5.499 0.994 -0.078 0.882 20.62 0.937 0.966 0.995 Super case-II transport

F4 8.218 0.983 -0.183 0.767 31.34 0.957 0.684 0.981 Anomalous

F5 7.855 0.996 -0.101 0.860 29.54 0.944 0.793 0.991 Anomalous

F6 7.306 0.998 -0.07 0.909 27.21 0.928 0.939 0.997 Super case-II transport

The flux value for formulation F4 was found to be maximum, which is 2.632±0.023 μg

cm-2 hr-1 and permeability coefficient was 1.32±1.07 ×10-3 cm hr-1. The results obtained

for permeation data is given in the Table 6.

Table 6: Permeation data analysis of Valsartan Transdermal patches

Sr. No

Formulation code

Flux (J) (μg cm-2 hr-1)

Diffusion coefficient

(cm2/h)

Permeability co efficient

(KP) (cm hr-1×10-3)

Enhancement ratio (ER)

1 F1 2.286±0.012 0.0113±0.6 1.14±1.51 - 2 F2 1.981±0.004 0.0098±0.252 0.99±1.56 - 3 F3 1.750±0.001 0.0086±0.577 0.87±3.07 - 4 F4 2.632±0.023 0.013±0.0001 1.32±1.07 1.152±0.0049 5 F5 2.501±0.003 0.0123±1.1 1.25±1.5 1.263±0.0039 6 F6 2.328±0.001 0.01148±0.577 1.16±2.37 1.330±0.0015



In the present work stability study was carried out for selected formulation F4 for one

month. The samples were evaluated for physicochemical parameters like thickness,

folding endurance, tensile strength, moisture content, drug content and drug release.

Results are the mean of triplicate observations ± SD. From comparison results, it was

concluded that the release of drug after stability period was nearly same as those of patch,

before the stability period. Hence, stability study indicates that the formulation is quite

stable at accelerated conditions. The results after stability period are given in Table 7.

Table 7: Accelerated stability study for Optimized formulation

Test Parameters Result before stability period

Result after stability period

Patch thickness (mm) 0.243±0.006 0.220±0.010 Weight uniformity (gm) 0.097±0.0015 0.0963±0.0015

Folding endurance 267±7.55 256.7±5.86 Moisture content (%) 1.72±0.606 2.41±0.59

Tensile strength (gm/cm2) 112.60±1.20 108.36±1.72 % elongation (% cm-2) 62.67±2.31 64.9±1.51

Drug content (%) 97.92±0.382 97.08±0.63 Table 8: In-vitro drug release data after stability period for optimized batch

Time (hrs)

In-vitro % CDR before stability period

In-vitro % CDR after stability period

0 0 0 1 20.58 18.70129 2 28.78 26.87577 3 36.06 34.62423 4 41.83 40.80464 5 50.77 48.9317 6 59.85 56.78737 7 66.27 62.76418 8 77.13 73.17268 9 86.66 80.5232 10 95.65 89.72165 11 98.89 93.78351 12 99.8 96.30928



Figure 9: In-vitro drug release data after stability period for optimized batch

CONCLUSION

The transdermal patch formulation was found to be efficacious, safe, stable and non

irritant to skin. The formulation F4 (HPMC K4M and sodium alginate using propylene

glycol as a plasticizer) was optimized and it showed release in concentration independent

manner. The above formulation gave a maximum drug diffusion of 99.8 % over a period

of 12 hours. The drug release kinetics of all fabricated patches follows zero order kinetics

and the mechanism of drug release from all formulations were swelling type. Further, ex-

vivo studies have to be performed to correlate with in-vitro release data for the

development of suitable controlled release patches for Valsartan.

As an extension of this work pharmacokinetic studies, in-vivo studies on higher animals

and controlled clinical studies on human beings will be carried out in future.

REFERENCES

1. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of

transdermal drug delivery. Nature Reviews, Drug Discovery 2004, 3: 115-124.



2. Smith DG, Cerulli A, Frech FH. Use of valsartan for the treatment of heart failure

patient not receiving ACE inhibitors: a budget impact analysis. Clin Ther 2005;

27(6): 951.

3. Criscione L, Bradley W, Buhlmayer P, Whitebread S, Glazer R, Lloyd P, Mueller

P, Gasparo MD. Valsartan: preclinical and clinical profile of an antihypertensive

angiotensin-II antagonist. Cardiovasc Drug Rev 1995; 13(3): 230-250

4. Yan J, Chen L, Chen S. Electrochemical behavior of valsartan and its

determination in capsules. Colloids Surf B Biointerfaces 2008; 67: 205-209

5. Brookman LJ, Rolan PE, Benjamin IS, Palmer KR, Wyld P, Lloyd PJ, et al.

Pharmacokinetics of valsartan in patients with liver disease. Clin Pharmacol Ther

1997; 62(3): 272–8.

6. Brunella C, Clelia DM, Maria IA. Improvement of solubility and stability of

valsartan by hydroxy propyl-beta-cyclodextrin. J Incl Phenom Macrocycl Chem

2006; 54: 289-294.

7. Rao SPK, Chowdhary KPR. Factorial studies on the effects of hydroxy propyl β-

cyclodextrin and poloxamer 407 on the solubility and dissolution rate of BCS

class II drugs. J Chrono Drug Deli 2011; 2(2): 89-93

8. Arora P, Mukherjee B. Design, development, physicochemical and in-vitro and

in-vivo evaluation of transdermal patches containing diclofenac diethyl

ammonium salt. J Pharma Sci 2002, 91(9): 2067-2089

9. Garala KC, Shinde AJ, Shah PH. Formulation and in-vitro characterization of

monolithic matrix transdermal systems using HPMC/Eudragit S 100 polymer

blends. Int J Pharm Pharma Sci 2009; 1(1): 108-120

10. Shivaraj A, Selvam RP, Mani TT, Sivakumar T. Design and evaluation of

transdermal drug delivery of ketotifen fumarate. Int J Pharm Biomed Res 2010;

1(2): 42-47.

11. Jayaprakash S, Halith SM, Firthouse MPU, Yasmin, Nagarjan M. Preparation and

evaluation of celecoxibe transdermal patches. Pak J Pharm Sci 2010; 23(3): 279-

283.



12. Rathore RPS, Chauhan CS, Naruka PS, Tanwar YS, Chauhan LS. Transdermal

formulation of terbutaline sulphate. Pharmacy online 2006.

13. Gannu R, Vishnu YV, Kishan V, Rao YM. Development of nitrendipine

transdermal patches: In vitro and Ex vivo characterization. Curr Drug Deliv 2007,

4: 69-76.

14. Kavitha K, Kumar DP. Development of transdermal patches of nicardipine

hydrochloride: An attempt to improve bioavailability. Int J Res Pharma Biomed

Sci 2011; 2(1): 285-293

15. Patel HJ, Patel JS, Desai BG, Patel KD. Design and evaluation of amlodipine

basilate transdermal patches containing film former. Int J Pharma Res Dev 2009;

7; 1-12.

16. Dey S, Malgope A. Preparation of carvedilol transdermal patch and the effect of

propylene glycol on permeation. Int J Pharm Pharma Sci 2010; 2(1); 137-143

17. Mamatha T, Rao VJ, Mukkanti K, Gannu R. Development of matrix type

transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro

characterization. J Pharm Sci 2010; 18(1); 74-81

18. Patel RP, Patel G, Baria A. Formulation and evaluation of transdermal patch of

aceclofenac. Int J Drug Deli 2009; 1: 41-51

19. Gavali P, Gaikwad A, Radhika PR, Sivakumar T. Design and development of

hydroxy propylmethylcellulose (HPMC) based polymeric film of enalapril

maleate. Int J Pharm Tech Res 2010; 2(1): 274-282

20. Latha S, Selvamani P, Thirunavukkarasu C, Kadambavadani R. Formulation

development and comparison in evaluation of transdermal drug delivery system

for anti-emetic therapy. Int J Res Pharma Biomed Sci 2011; 2(2): 525-528

For Correspondence: Mitali Ghinaiya Email: [email protected]

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FORMULATION AND EVALUATION OF TRANSDERMAL PATCH OF AN