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Rekha Sudam Kharat* et al. International Journal Of Pharmacy & Technology

IJPT| June-2016 | Vol. 8 | Issue No.2 | 12609-12628 2609

ISSN: 0975-766X CODEN: IJPTFI

Available Online through Research Article

www.ijptonline.com FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES OF NICARDIPINE

HYDROCHLORIDE Rekha Sudam Kharat*, Ritesh Suresh Bathe.

Department of Pharmaceutics, Sahyadri College of Pharmacy, Methwade,

Sangola-413307, Solapur, Maharashtra, India.

Email: [email protected]

Received on 12-05-2016 Accepted on 05-06-2016

Abstract

The present study was carried out to develop the transdermal patches Containing Nicardipine Hydrochloride with

different polymers of PVA, HPMC, PVP K30 and EC was added in the formulation Polyethylene glycol (PEG400) used

as a plasticizer , DMSO and eugenol is used as penetration enhancers. Solvent evaporation method was used for the

formulation of patches. The patches showed satisfactory folding endurance and tensile strength. And it indicated good

physical stability. The drug-excipients compatibility studies were performed by Fourier Transform Infrared

spectrophotometer (FTIR). The diffusion studies were performed by using modified Franz diffusion cell. In -vitro drug

permeation test was carried for 24hrs. F9 contain eugenol is used as natural penetration enhancer it shows maximum drug

permeation 94.61% of at the end of 24hrs. Due to which reported that penetration enhancers had functional groups with

hydrogen- bonding ability effectively improving the drug transport through skin and also improvement in the partitioning

of the drug to stratum corneum. The mechanism of drug permeation was followed diffusion controlled by zero order and

Higuchi matrix kinetics respectively.

Keywords: Nicardipine Hydrochloride, Matrix type transdermal patch, PVA, PVPK30, HPMC, EC, PEG400, Solvent

evaporation method.

Introduction

Transdermal drug delivery system (TDDS) established itself as an integral part of novel drug delivery systems which

employ a structure as a reservoir for the drugs. [1]

The administration of drug by transdermal route offers the advantage of

being relatively painless. The appeal of using the skin as portal of drug entry lies in case of access, its huge surface area,


IJPT| June-2016 | Vol. 8 | Issue No.2 | 12609-12628 Page 12610

and systemic access through underlying circulating network and noninvasive nature of drug delivery. Self-contained,

discrete dosage form which, when applied to the intact skin, deliver the drug, through the skin, at a controlled rate to the

systemic circulation called transdermal delivery was first used in 1981. Transdermal drug delivery offers controlled

release of the drug into the patient, it enables a steady blood level profile, resulting in reduced systemic adverse effects

and, sometimes, improved efficacy over other dosage forms. [2]

For transdermal products the goal of dosage design is to maximize the flux through the skin into the systemic circulation

and simultaneously minimize the retention and metabolism of the drug in the skin.[3]

Transdermal drug delivery is the

delivery of drugs across epidermis to achieve systemic effects. The success of transdermal patches lies in their

commercialization. Transdermal patches control the delivery of drugs at controlled rates by employing an appropriate

combination of hydrophilic and lipophilic polymers. [4]

Nicardipine hydrochloride [2-(Benzyl (methyl) amino) ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-

3,5-dicarboxylate hydrochloride] is rapidly and completely absorbed from the gastrointestinal tract but is subject to

saturable first pass hepatic metabolism. Following oral administration of nicardipine hydrochloride was shown to be

rapidly and extensively metabolised in the liver and to be rapidly eliminated from plasma through urine and faeces,

mainly as inactive metabolites. Bioavailability of about 35% has been reported after a 30-mg dose at steady state.

Administration of nicardipine hydrochloride following a meal reduced the bioavailability. The pharmacokinetics of

nicardipine hydrochloride are non-linear due to the saturable first-pass hepatic metabolism and an increase in dose may

produce a disproportionate increase in plasma concentration. The terminal plasma half-life is about 8.6 hours, thus steady-

state plasma. Delivery via the transdermal route is an interesting option in this respect because transdermal routeis

convenient and safe. [5-7]

The aims of the present study were to develop transdermal patches of Nicardipine Hydrochloride with different ratios of

hydrophilic and hydrophobic polymer combinations such as Polyvinyl Alcohol, Polyvinyl Pyrrolidone K30, HPMC, EC,

and Polyethylene Glycol 400 as a plasticizer, DMSO and Eugenol is used as penrtration enhancer by using solvent

evaporation techniques and performed physicochemical characterization and In-vitro permeation studies. The purpose was

to provide the delivery of the drug at a controlled rate across intact skin to improve bioavailability and hypertension

control for longer period from transdermal patches.



Materials and Methods:

Materials

Nicardipine Hcl was received as a gift sample from Kekule Pharma Limited, Hyderabad. Polyvinyl Alcohol, Polyvinyl

Pyrrolidone K30, HPMC, EC, Polyethylene Glycol 400, Methanol, DMSO, Eugenol obtained from Seva fine Chemical

Ltd, Mumbai. All other materials and chemicals used were of either pharmaceutical or analytical grade.

Formulation of transdermal patches:

Patches compose of different ratio of polymers, Polyvinyl pyrrolidone (PVP), Ethyl cellulose, HPMC and PEG400 where

prepared by solvent evaporation techniques using bangles. The bottom of the bangle was wrapped with aluminum foil on

which backing membrane was cast by pouring 5%w/v aqueous PVA solution followed by drying at 500C for 8hours.Drug

matrix was prepared by dissolving requisite amount of drug (Nicardipine hydrochloride) and EC in methanol. To this

solution PEG400 (40%w/w of polymer composition) was added and stirred. The uniform dispersion obtained was casted

on PVA backing membrane and dried at room temperature for 24hrs.The rate of solvent evaporation was controlled by

inverting a glass funnel over the Petri plate.

The dry Patches were removed and wrapped in aluminum foil and kept in a desiccator until used. Then the solution was

poured on the Petri dish having surface area of 63.58 cm2. Then the patches were cut into 2x2 cm

2.

Fig. 1: Prepared transdermal patch of Nicardipine hydrochloride.



Table 1: - Composition of various formulation of Nicardipine Hydrochloride patches.

Name of ingredient F1 F2 F3 F4 F5 F6 F7 F8 F9

Drug (mg) 30 30 30 30 30 30 30 30 30

Methanol (ml) 3 3 3 3 3 3 3 3 3

PEG400 (%) 40 40 40 40 40 40 40 40 40

PVA (%) 5 5 5 5 5 5 5 5 5

HPMC (%) 2 5 10 - - - - - -

PVPK30 (%) - - 2 5 10 - - -

EC (%) - - - - 2 5 10

DMSO (%) - - - - - - - 5 -

Eugenol (%) - - - - - - - - 5

Characterization of Transdermal Patches:

In the pre-formulation studies λmax, IR, solubility, partition coefficient and melting point of drug was determined.

The prepared transdermal patches were evaluated for evaluation parameters to check the integrity of formulation such as

thickness uniformity, weight uniformity, drug content uniformity, folding endurance, tensile strength, percentage

elongation, flatness, moisture content, moisture uptake, swelling index, In-vitro drug diffusion through cellophane

membrane.

Characterization of API and Polymer:

Compatibility studies:

IR spectroscopy study was carried out to determine the physical or chemical interaction between drug and polymers. The

combinations were compared with the spectra of pure drug and individual polymer. The principle peak obtained for the

combinations were almost similar to that of the drug. The FTIR spectra of drug, PVA, PVPK30, EC and HPMC, drug –

PVA-PVPK30, drug-PVA-EC and drug–PVA-HPMC did not shown any changes. The possibility of interaction was ruled

out as there was no major shift in the absorption bands of drug and the formulation.



Fig. 2: FTIR of Pure Nicardipine Hydrochloride.

Table 2: Interpretation data FTIR of Pure Nicardipine Hydrochloride.

Sr .No Functional Group Standard Value Obtained Value

1 Nitro group 1550-1350 cm-1

1502 cm-1

2 Amine group 1350-1000 cm-1

1052 cm-1

3 Ester 1750-1730 cm-1

1737 cm-1

4 C-H 1450 cm-1

1443 cm1

5 Aromatic substitution 750 cm-1

750 cm-1

Fig.3: FT-IR Spectra of Nicardipine Hydrochloride + Polyvinyl alcohol+ Hydroxy propyl methyl cellulose.



Fig. 4: FT-IR Spectra of Nicardipine Hydrochloride + Polyvinyl alcohol+ Polyvinyl-pyrrolidone K30.

Fig. 5: FT-IR Spectra of Nicardipine Hydrochloride + Polyvinyl alcohol+ Ethyl Cellulose.

Thickness: [8-10]

The thickness of patches was measured by digital vernier calipers with least count 0.001mm. The thickness uniformity

was measured at five different sites and average of five readings was taken with standard deviation

Weight variation: - [11-15]

The three disks of 2x2 cm2was cut and weighed on electronic balance for weight variation test. The test was done to check

the uniformity of weight and thus check the batch- to- batch variation.



Percentage Elongation: -

The percentage elongation break is to be determined by noting the length just before the break point from the below

mentioned formula.

Where,

L1- is the final length of each strip

L2- is the initial length of each strip.

Folding endurance: [16-20]

This was determined by repeatedly folding one patch 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.

Tensile Strength: [21]

The tensile strength was determined by the apparatus designed as shown in fig 5.2.The instrument was designed such that

it had horizontal wooden platform with fixed scale and attachments for two clips that holds transdermal patch under test.

Out of the two clips one was fixed and other was movable. Weights were hanged to one end of pulley and the other end of

pulley was attached with movable clip.

The wooden plat form was such fitted that it would not dislocate while the test is running. Three strips of patch were cut

having 2cm length and 2cm breadth. The thickness and breadth of strips were noted at three sites and average value was

taken for calculation. The rate of change of stress was kept constant with the increment of 0.5g per 2 minutes. The

elongation was observed and the total weights taken were used for calculation. The tensile strength was calculated by

using following formula.

Where,

L - Length, b – Thickness,

a – Width, ΔL- Elongation at break



Fig .6: Assembly for tensile strength.

Moisture content: [22]

The films were weighed and kept in desiccator containing calcium chloride at 40°C in a dryer for at least 24 hrs or more

until it showed a constant weight. The percentage of moisture content was the difference between constant weight taken

and the initial weight and as reported in terms of percentage by weight moisture content.

Moisture uptake study: [23]

After films, of which the size is 2x2 cm2, were put in a desiccator with silica gel for 24 hrs and weighed, the patches were

transferred to another desiccator containing saturated solution of potassium chloride solution (relative humidity 85%)

after equilibrium was attained, the patches were taken out and weighed. Moisture uptake capacity was calculated

according to the following equation:

Swelling index: [24]

The patches of 2x2cm² was weighed and put in a Petri dish containing 10 ml of double distilled water and were allowed to

imbibe. Increase in weight of the patch was determined at preset time intervals, until a constant weight was observed. The

degree of swelling (% S) was calculated using the formula

S (%) = Wt – Wo/Wo x 100

Where, S is percent swelling, Wt is the weight of patch at time t and



Wo is the weight of patch at time zero

Drug content: [25]

The film sample of 2x2cm2 was cut and dissolved in 100 ml volumetric flask containing phosphate buffer (pH7.4) the

flask was sonicated for 15 min. A blank was prepared in the same manner using drug free placebo film of same area. The

solution was then filtered using a 0.45µm filter and the drug content was analyzed at 238nm by UV spectrophotometer.

Diffusion studies: [26, 27]

Diffusion Cell:

The glass Franz diffusion cell was used for release studies. The cellophane membrane was mounted between donor and

receptor compartment.The transdermal patch was fixed on between donor and receptor compartments were clamped

together and placed in a water bath maintained at 37 ± 0.5°C. The volume of receptor cell was 25 ml and the effective

surface area available for permeation was 4.9062 cm2. The receptor compartment filled with pH 7.4 phosphate buffer. The

hydrodynamics of the receptor fluid was maintained by stirring the fluid at 600 rpm with star head magnet. Samples 2 ml

were withdrawn at specific interval of time. The same volume of phosphate buffer pH 7.4 was added to receptor

compartment to maintain sink conditions and the samples were analyzed at 238 nm UV-spectro-photomertically.

Fig.7: Diffusion cell.

Stability studies: [28-30]

The stability studies of the formulations were carried out as per ICH guidelines. The study was conducted at temperature

of 40°C and 75 % RH. Transdermal systems of 2x2 cm2 area were wrapped individually in a butter papers, packed in

aluminum foils and placed in petri-dishes. These petri-dishes containing patches were stored at 40°C and 75 % RH for a



period of one month. The samples were observed for physical changes like colour, flexibility, etc. The drug content was

determined at an interval of one month.

Result and Discussion

Table 3: Physicochemical evaluation data of Nicardipine Hydrochloride Transdermal patches.

Formulation

Code

Thickness

(mm)

Weight variation

(mg)

% Drug

Content

Folding

endurance

Tensile strength

Kg/mm2

F1 0.35±0.01 0.233±0.01 93.94±3.31 134.6±11.06 2.46±0.80

F2 0.34±0.03 0.216±0.006 92.61±3.12 134±13.22 3.3±0.78

F3 0.35±0.003 0.219±0.011 91.41±2.91 132±10.53 2.9±1.25

F4 0.39±0.004 0.226±0.009 93.39±2.02 127±22.33 3.84±1.90

F5 0.38±0.03 0.221±0.020 94.40±1.54 134±18.35 4.49±1.00

F6 0.41±0.06 0.229±0.013 94.68±2.41 145±24.0 5.06±2.79

F7 0.37±0.04 0.221±0.017 92.81±2.89 132±9.53 3.66±0.85

F8 0.42±0.09 0.229±0.011 94.70±2.12 131.6±22.03 4.6±2.78

F9 0.35±0.08 0.225±0.019 94.81±1.43 146±15.04 3.93±1.87

Table 4: Physicochemical evaluation data of Nicardipine Hydrochloride Transdermal patches.

Formulation

Code

% Elongation % Moisture

Content

% Moisture

uptake

Swelling

index

F1 23.80±2.13 1.93±0.45 5.8±1.73 23.40±2.26

F2 28.05±2.26 2.0±0.85 6.13±2.66 22.84±1.28

F3 22.42±1.05 2.5±0.88 5.8±1.55 24.19±0.90

F4 28.05±4.75 3.1±1.27 4.86±3.15 25.99±1.16

F5 22.42±2.52 3.16±1.60 3.4±1.70 23.44±0.77

F6 29.61±3.21 3.23±2.77 4.46±1.05 24.18±1.39

F7 26.11±5.21 3.2±1.85 4.7±0.95 25.50±2.11



F8 25.85±2.61 3.6±1.90 5.3±1.24 24.28±2.32

F9 26.26±4.16 2.7±0.98 3.6±3.9 25.65±0.71

Table 5: In-vitro Drug Permeation of Nicardipine Hydrochloride From F9 through cellophane membrane.

Time in

(hrs)

Square

root of

time (hrs)

Log time

(hrs)

F9

% Drug

Permeated

Log % Drug

Permeated

Log % Drug

Retained

2 1.41 0.30 9.57 0.98 1.95

4 2.00 0.60 16.77 1.22 1.92

6 2.45 0.78 28.13 1.44 1.85

8 2.83 0.90 39.47 1.59 1.78

10 3.16 1.00 50.14 1.70 1.69

12 3.46 1.08 62.97 1.81 1.54

16 4.00 1.20 73.07 1.86 1.43

20 4.47 1.30 80.94 1.90 1.28

24 4.90 1.38 94.61 1.97 0.73

Table 6: In-vitro Drug Permeation of Nicardipine Hydrochloride Data Batches F1-F9.

Time (hrs) F1 F2 F3 F4 F5 F6 F7 F8 F9

2 5.94 6.99 8.71 13.64 5.98 9.97 4.8 6.9 9.57

4 16.33 15.29 13.96 25.74 16.21 21.61 13.98 18.94 16.77

6 25.67 30.33 27.69 35.25 25.67 33.12 23.69 31.51 28.13

8 36.87 37.68 38.26 44.35 33.89 41.66 31.94 41.65 39.47

10 44.31 52.14 45.63 50.31 44.61 52.97 42.68 51.28 50.14

12 55.67 59.49 54.69 61.99 53.74 61.87 53.61 62.34 62.97

16 63.84 65.11 63.87 72.38 65.98 72.58 64.89 72.97 73.07

20 76.91 76.43 69.64 80.13 72.94 79.94 75.98 82.13 80.94

24 87.36 82.64 77.94 89.23 88.31 84.73 85.64 90.36 94.61


IJPT| June-2016 | Vol. 8 | Issue No.2 | 12609-12628 620

Fig. 8 Comparative In-vitro Permeation Profile of Nicardipine Hydrochloride

According to Zero Order Kinetics Formulations F1-F9.


According to First Order release Kinetics Formulations F1-F9.


According Higuchi Matrix Kinetics for Formulations F1- F9.


According to Korsmeyer-Peppas Kinetics for Formulations F1- F9.



Table 7: In-vitro Permeation of Nicardipine Hydrochloride patches through Cellophane membrane.

Sr. No Zero

Order

First

Order

Higuchi Korsmeyer-Peppas Best Fit Model

(r2) (r

2) (r

2) (r

2) (n)

F1 0.997 0.911 0.998 0.879 1.41 Higuchi matrix

F2 0.992 0.971 0.989 0.854 1.10 Zero order

F3 0.994 0.981 0.992 0.983 1.03 Zero order

F4 0.995 0.928 0.997 0.916 0.87 Higuchi matrix

F5 0.995 0.881 0.996 0.886 1.14 Higuchi matrix

F6 0.993 0.974 0.992 0.872 0.98 Zero order

F7 0.994 0.920 0.998 0.882 1.20 Higuchi matrix

F8 0.998 0.932 0.997 0.856 1.11 Zero order

F9 0.997 0.852 0.998 0.920 1.06 Higuchi matrix

Stability Study:

Present study was carried out to check the permeation and physical appearance of optimized batch F9 was selected as an

optimum batch and the stability study was carried out at accelerated conditions of 400C and 75% RH at an interval of one

month.

Table 8: Stability Study for F9 batch:

Sr. no Evaluation Parameter At oth

day After 30 days

1 Thickness (mm) 0.39 ± 0.096 0.37 ± 0.066

2 Weight variation 0.225±0.011 0.223 ± 0.018

3 % Drug Content 94.81 ± 1.43 93.67 ± 1.23

4 Folding endurance 146 ± 15.04 144 ± 19.67

5 Tensile Strength Kg/mm2 3.93 ± 1.87 3.43 ± 1.68

6 % Elongation 26.26 ± 4.16 25.42 ± 4.3

7 % Moisture content 2.7 ± 0.984 2.5 ± 0.929

8 % Moisture uptake 5.2 ± 2.5 4.83 ± 3.03

9 Swelling index 25.65 ± 0.71 23.47 ± 0.99



Table 9: Drug permeation study:

Time in

(hrs)

Cumulative % Drug

permeated (At 0 day)

Cumulative % Drug

Permeated (After 30 days)

2 9.57 8.23

4 16.77 15.71

6 28.13 27.39

8 39.47 36.93

10 50.14 49.67

12 62.97 61.38

16 73.07 72.03

20 80.94 78.82

24 94.61 93.50

Compatibility studies:

The combinations were compared with the spectra of pure drug and individual polymer.

The principle peak obtained for the combinations were almost similar to that of the drug.

The FTIR spectra of drug, PVA, PVPK30, EC and HPMC, drug –PVA-PVPK30, drug-PVA-EC and drug–PVA-HPMC

did not shown any changes. The possibility of interaction was ruled out as there was no major shift in the absorption

bands of drug and the formulation.

FTIR:

FTIR spectrum for Nicardipine hydrochloride indicated characteristics peaks belonging to measure functional groups such

as principle peaks at wave number at 1507 cm-1

due to NO2 stretching , at 1052 cm-1

owing to –N-H stretching, at 1737

cm-1

owing to –C=O ,at 750 cm-1

due to aromatic substitution and at 1443 cm-1

due to –C-H deformation as shown in

(Figure.2) respectively.

Formulations of Transdermal Patches:

Nine formulations of Nicardipine Hydrochloride transdermal Patches compose with different polymers PVA, PVPK30,

Ethyl cellulose, HPMC and PEG400 as a plasticizer also DMSO and Eugenol is used as penrtration enhancer. Where

prepared by solvent evaporation techniques using bangles.



The bottom of the bangle was wrapped with aluminum foil on which backing membrane was cast by pouring 5%w/v

aqueous PVA solution followed by drying at 50°C for 8hrs.Drug matrix was prepared by dissolving requisite amount of

drug (Nicardipine hydrochloride) and EC in methanol. To this solution PEG400 (40%w/w of polymer composition) was

added which is shown in (Table-1).

The formulations are subjected to evaluation for different parameters which are enlisted in the (Table-3) and (Table-4).

The prepared transdermal therapeutic systems were thin, flexible and smooth. The solvent evaporation method used for

the preparation of patches was found satisfactory.

Physicochemical Evaluation:

The thickness of the patches varied from 0.34 ± 0.035 to 0.42 ± 0.096mm. The values obtained for all the formulations are

given in the table. The low SD values in the Patches thickness measurements ensured uniformity of thickness in each

formulation (Table-3). The weight variation was to be in the range of 0.216 ± 0.006 to 0.233 ± 0.011mg. The values for

all the formulations are tabulated in the table. The weights of all transdermal systems were found to be uniform with their

low SD values (Table-3).

The drug content uniformity was determined for all transdermal systems. The results of this study revealed that, the drug

content was uniform in all systems with relatively low SD values i.e. 91.41 ± 2.91 to 94.81 ± 1.43 (Table-3).

The folding endurance of patch is frequently used to estimate the ability of patch to withstand repeated bending, folding

and creasing and may encountered as a measure of the quality of the patch .The folding endurance was found to be in the

range of 127 ± 6.4 to 146.66 ± 15.04 number of folds. The values for all eleven formulations are given in the table. This

data revealed that the patches had good mechanical strength along with flexibility (Table-3). Tensile strength of the patch

was determined to measure the ability of patch to withstand rupture. The tensile strength was found to be in the range of

2.46±0.80 to 5.06±2.79 Kg/mm2. The formulation F6 showed the best tensile strength. The values for all the patch are

tabulated in the table (Table-3). The % elongation was found to be in the range of 22.42±1.05 to 29.61±3.21%. The

results obtained for all the formulations are tabulated in the (Table -4).

The percentage moisture content study was carried out to check the integrity of the transdermal patches at dry condition.

The moisture content was found to be in the range of 1.19 ± 0.45 to 3.6±1.9. The values for all the patches are tabulated in

the respective table. The percentage moisture uptake test was carried out to check physical stability or integrity of the



patch at humid condition. Moisture uptake was found in the range of 3.4±1.70 to 6.13±2.66 (Table- 4). Swelling index

was found in the range of from 22.42±1.12 to 29.61±3.21 (Table-4).

In vitro Drug Permeation Kinetics:

The results obtaining in In-vitro release studies were plotted in different model of data treatment as follows:

Cumulative percent drug permeated vs. time (Zero order kinetics)

Log Cumulative percent drug remaining to be permeated vs.time (First order kinetics)

Cumulative percent drug permeated vs. square root of time (Higuchi Matrix plot)

Log Cumulative percent drug permeated vs. log time ( Korsmeyer-peppas plot)

The penetration of drug from the Patches is dependent on the type of polymer as well used concentration. In-vitro

permeation studies were carried out by using franz diffusion cell through cellophane membrane in Phosphate Buffer pH

7.4. In drug Permeation study the formulation F9 contain eugenol is used as natural penetration enhancer it shows

maximum drug permeation 94.61% of at the end of 24hrs. Due to which reported that penetration enhancers had

functional groups with hydrogen- bonding ability effectively improving the drug transport through skin and also

improvement in the partitioning of the drug to stratum corneum. The drug permeation data was plotted for Zero order,

First order, Higuchi model and Korsmeyer-Peppas model to evaluate the permeation pattern of the dosage form. From

these plots, kinetic values of the drug permeation were determined. In Zero order plot the r2value was obtained 0.992 to

0.998, 1storder it was 0.852 to 0.981 for Higuchi model it was 0.992 to 0.998 and for Korsmeyer-Peppas it was 0.852 to

0.983 describing the permeation rate independent of concentration of drug. Hence, formulation prepared containing PVA,

PVPK30, EC and HPMC fit into zero order and Higuchi model behavior. The process of drug permeation in most

controlled permeation devices including transdermal patches is governed by diffusion and the polymer matrix has a strong

influence on the diffusivity as the motion of a small molecule is restricted by the three–dimensional network of polymers

chain. The In-vitro permeation profile could be best expressed by Higuchi’s equation for the permeation of drug from the

matrix. from a homogeneous- polymer matrix type delivery system that depends mostly on diffusion characteristics. To

know the mechanism of drug permeation release kinetics from these formulations, the data were treated according to;

Korsmeyer-Peppas model (log cumulative percentage of drug permeated vs.log time) equations (Figure.11 ) All

formulations F1 to F9 showed high linearity with slope (n) values ranging from 0.87 to 1.41 this (n) value indicating that



the drug permeation is controlled by more than one mechanism, The exponent (n) values was obtained for optimized

formulation F9 by fitting data into Korsmeyer-Peppas equation i.e. 1.065 indicating diffusion of drug from the

formulation followed Non Fickian case II.

Stability Studies:

Stability is the essential factor for quality, efficacy and safety of drug product. The drug product with insufficient stability

can result in change of their physical as well as chemical characteristics. The selected formulations namely, F9 were

subjected for stability studies and observed for changes in color, appearance, flexibility and drug content at a temperature

of 400C and 75%RH, at an interval of one month.

There were no physical changes in appearance, flexibility and color and physicochemical evaluation parameter was

slightly changed (Table-8). The percentage of degradation with respect to drug content was observed 1-2 %. Hence, the

formulations were stable (Table-9).

Conclusion:

Transdermal drug delivery systems are ideally suited for drugs that undergo hepatic first pass metabolism along with a

short elimination half-life. Hypertension being a very common disorders leading to preventable death & been treated with

different classes of drugs in form of several dosages. Oral being the popular route of administration for these

antihypertensive has come across several demerits.

The matrix type transdermal drug delivery system of Nicardipine Hcl was successfully designed & developed by trial and

error method. Results of FT-IR revealed that there was no chemical interaction between the drug and the polymer used.

The prepared transdermal patches were, thin, smooth and flexible, uniformity in drug content, physicochemical properties

were observed with their low SD values. Among the formulations F9 was found to be best with respect to drug release rate

i.e. 94.61% at the end of 24 hr. F9 contain eugenol is used as natural penetration enhancer it shows maximum drug

permeation. Due to which reported that penetration enhancers had functional groups with hydrogen- bonding ability

effectively improving the drug transport through skin and also improvement in the partitioning of the drug to stratum

corneum.

From all the formulations shows zero order and Higuchi matrix kinetic releases the drug by Non‐Fickian case II

mechanism. From the above result formulation F9 was found to be best formulation for transdermal delivery of



Nicardipine Hydrochloride that complied with all the parameters. However In-vivo experiments need to be carried out to

know the permeation pattern and bioavailability of drug from the transdermal patches and thus enabling to establish In-

vitro In-vivo correlation.

Acknowledgement:

The authors are highly thankful to the Sahyadri College of Pharmacy, Methwade, Sangola, Solapur, Maharashtra, India

for proving all the facilities to carry out the research work.

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Corresponding Author:

Rekha Sudam Kharat*,

Email: [email protected]

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