Development and Evaluations of Transdermal Delivery of Selegiline Hydrochloride

Volume 2, Issue 6, June 2017 International Journal of Innovative Science and Research Technology
ISSN No: - 2456 2165
Development and Evaluations of Transdermal

Delivery of Selegiline Hydrochloride
Sandip A. Murtale*, Doddayya Hiremath, Vishnu A. Kangralkar, Veerrendra C. Yeligar, Sachinkumar V. Patil,
Shitalkumar S. Patil
1
Department of Pharmaceutics N.E.T Pharmacy College, Mantralayam Road, Raichur-584103, Karnataka, India.
2
Department of Pharmaceutics Ashokrao Mane College of Pharmacy, Peth Vadgaon,kolhapur
murtalesandy@gmail.com
Abstract :- A reservoir type transdermal film for significantly increase the number of drug molecules suitable
delivery of Selegiline hydrochloride (SH) is a SSRI 2
for transdermal delivery .
(selective serotonin reuptake inhibitors) agent with anti-
depressant activity and acts by inhibiting MAO type B Selegiline, a preferential MAO-type B inhibitor, is
inhibitor. Studies were carried out to investigate the currently used in the treatment of depression. Selegiline
effect of permeation enhancers on the in vitro Hydrochloride has steady state half-life of 2 hours, oral dose
permeation of SH across cellophane/ rat skin. Films were of 10 mg daily, oral bioavailability 4.4% and protein
prepared by using hydroxy propyl methyl cellulose 3, 4
binding of 94% . Selegiline is readily absorbed from
(HPMC), polyvinylalcohol (PVA) and methyl cellulose gastrointestinal tract from conventional preparations and
(MC) polymers by incorporating glycerine as plasticizers crosses the blood brain barrier. It undergoes extensive
using solvent casting method. A total of eighteen first pass metabolism in the liver to produce at least 5
formulations were prepared by using different drug metabolites excreted mainly in the urine and about 15%
polymer ratio of 1:1, 1:2 and 1:3 from these ratios 1:3 5
ratio of polymers is selected for incorporated terpenes as appears in the feaces to improve its therapeutic efficacy by
permeation enhancers in same concentrations. The improving bioavailability, patient compliance and as well as
maximum percent of drug permeation was observed to reduce the frequency of dosing and side effects, the
with PVA monolithic transdermal film containing 5% transdermal drug delivery approach was considered to be
eucalyptol (F12). The in vitro release studies revealed better suitable for Selegiline hydrochloride.
that eucalyptol showed better permeation enhancement The objective of the present work was to formulate and
than d-limonene and menthol the release was sustained evaluate the Selegiline hydrochloride the form of
up to 24 h and it follows fist-order kinetics. The release reservoir type controlled TDDS for in vitro release,
flux of selegiline hydrochloride from different permeation, and mechanical properties. To avoid the oral
transdermal films prepared in the range of 0.114 to 0.036 tablet undergoes extensive first pass metabolism and other
2 relented side effects.
g/cm /hr. All the films were found to be stable at 37C
and 45C with respect to their physical parameters.
Key words: Selegiline hydrochloride (SH), transdermal II. MATERIALS AND METHODS
films, in-vitro release and in- vivo studies.
2.1 Materials
I. INTRODUCTION
Selegiline hydrochloride was obtained as a gift sample
The transdermal route now ranks with oral treatment as the from Embio Limited, Mumbai. Hydroxy propyl methyl
most successful innovative research area in drug delivery, cellulose was gift sample from Colorcon Ltd, Goa
with around 40% of the drug delivery candidate products Polyvinyl alcohol Ethyl, cellulose and Methyl cellulose
under clinical evaluation related to transdermal or dermal was purchased from S.D Fine Chemicals Pvt Ltd,
system. The worldwide transdermal patch market Mumbai. All other chemicals and reagents used were of
approaches two billion pounds, based on some drugs analytical reagentgrade.
including scopolamine, nitroglycerine, clonidine, estrogen,
testosterone, fentanyl, and nicotine, with a lidocaine patch 2.2 Preparation of drugreservoir
soon to be marketed. The success of a dermatological drug
to be used for systemic drug delivery depends on the ability The polymeric solution was prepared by dissolving the
of the drug to penetrate through skin in sufficient quantities required quantity of polymer in distilled water (2.5 ml)
1 and glycerine (30% w/w of polymer) was added as
to achieve the desired therapeutic effect. However, the
plasticizer to this solution under stirring. The weighed
highly organized structure of stratum corneum forms an
amount of Selegiline hydrochloride was added to the
effective barrier to the permeation of drugs, which must be
above solution. After proper mixing the casting solution
modified if poorly penetrating drugs are to be administered.
2
The use of chemical penetration enhancers would was pouredinacleanglassb angle(anareaof9.61cm )which
IJISRT17JU173 www.ijisrt.com 391

ISSN No: - 2456 2165
is placedon the mercury surface. The films were dried at

2.3.6. Tensile Strength10
room temperature for 24 hrs. The dried films thus
obtained were cut by cork borer into circular discs of
14
2 Tensile strength of the film was determined with
definite size of 20 mm diameter (an area of 1.539 cm )
Universal Strength Testing Machine (Hounsfield,
containing 10 mg of drug.
Slinfold, Horsham, U.K). The sensitivity of the machine
was 1g. It consisted of two load cell grips. The lower one
2.2.1. Preparation of rate limiting membrane was fixed and upper one was movable. The test film of
2
The rate controlling membrane was prepared by size (4 /1 cm ) was fixed between these cell grips and
dissolving required quantity of ethyl cellulose in force was gradually applied till the film broke. The
chloroform. Dibutyl phthalate (30% w/w of polymer) tensile strength of the patch was taken directly from the
was added as plasticizer. The polymeric solution was 2
dial reading in kg/cm .
poured on a clean glass petridish and dried at room
temperature for 12 hrs. Circular discs of 20mm diameter 2.3.7. Drugcontent11
were cut using cork borer.
Specified area of patch is to be dissolved in a suitable
solvent in specific volume. Then the solution is to be
2.2.2 Preparation of transdermal films filtered through a filter medium and analyze the drug
contain with the suitable method (UV or HPLC
The reservoir films containing the drug were sandwiched technique). Each value represents average of three
in between the rate controlling membranes. They were different samples.
fixed by applying chloroform on the edges of the rate
controlling membrane.
2.4. Experimental procedure
2.3. Physicochemical e valuation of films Selegiline 12
hydrochloride transdermal films 2.4.1. In vitro release studies
In vitro skin permeation studies were performed by using

2.3.1. Uniformity of weight6 a Franz diffusion cell with a receptor compartment
capacity of 65 ml. The excised rat abdominal
2 skin/cellophane was mounted between the donor and
The film was cut into 10 patches of 1cm each and their
average weight was calculated. Percentage deviation receptor compartment of the diffusion cell. The
from average weight for each patch was also determined. formulated patches were placed over the skin. The
receptor compartment of the diffusion cell was filled with
2.3.2. Thickness7 phosphate buffer pH 7.4. The whole assembly was fixed
on a magnetic stirrer, and the solution in the receptor
Patch thickness was measured using micrometer at three compartment was constantly and continuously stirred
different places and the mean value plus standard using magnetic beads at 50 rpm; the temperature was
1
deviation (S.D.) was calculated. maintained at 32 0.5 C. The samples were withdrawn at
different time intervals and analyzed for drug content
2.3.3. Moisture content spectrophotometerically. The receptor phase was
replenished with an equal volume of phosphate buffer at
The films were weighed and kept in a decicator each sample withdrawal. amounts of drug permeated per
containing calcium chloride at room temperature for 24 square centimeter of patches were plotted against time.
hours. The films were reweighed after deciccant.
2.3.4. Moisture absorption8 2.4.2. In vitro permeation study of optimized transdermal
13
film cross rat abdominalskin Preparation of the rat skin
The weighed films were kept in a decicator at room
temperature for 24 hours. Then they were taken out and The experiment was conducted according to the protocol
exposed to 75% relative humidity (saturated solution of approved by the institutional animal ethics commitee
sodium chloride) (IAEC). The experiment was conducted according to the
2.3.5. Folding endurance9 guidelines of CPCSEA (Committee for the purpose of
control and supervision of experiment on animal). The
It was determined by repeatedly folding a small strip of male abdominal rats were sacrificed by decapitation. The
film at the same place till it break. The number of time, fresh abdominal skin was excised from male albino rat
the film could be fold at the same place without breaking weighing 170-190 g. The abdominal skin of excised
gave the folding endurance value. The average of the hairless rat skin was separated along the epidermal
three reading was calculated. junction. The hair of skin was removed using
depilatories. The process of the removal of hair did not

ISSN No: - 2456 2165
alter the skin properties and delivery of the drug. It was 17

2.6. Kineticstudy
kept at water bath maintained 60C for exactly 50 sec.
The heat treated skin was cleared of it subcutaneous fatty
To know the mechanism of drug release from these
substance and immediately kept in refrigerator at 10C.
formulations, the data were treated according to first-order
This step maintained integrity and viability of theskin.
(log percentage of drug to be released vs. time), Higuchis
(percentage of drug released vs square root of time), and
Permeation studies
zero-order (percentage of drug released vs time) patterns.
The permeation study were carred out by same procedure 18
2.7. Stability Studies
as used in in vitro release studies, except for the
cellophane membrane the excised rat abdominal skin was The selected transdermal patch were wrapped with
used as a membrane. aluminum foil and stability studies were carried out
o
2.4.3. In vivo studies according to ICH guidelines at 402 C/755%RH for one
month by storing the samples in stability chamber.
2.4.3.1. Anti-depressent activity14 III. RESULTS AND DISCUSSION
Male mice (20-25 gm) were used for testing the Anti- All the patches prepared with different polymer
depressent activity. Groups of 6 animals were treated concentration (1:1, 1:2 and 1:3 Drug: polymer ratio) were
with the test compound (the film being attached dorsal found to be flexible, smooth, opaque, non-sticky and
surface of mice) 30 min. prior to testing. After homogeneous in nature. This may be due to the presence of
application of patch, mice are suspended from a height plasticizer.
58 cm above a table top and the fixed wring a The weights of transdermal films were determined by
adhesive tape placed approximately 10 cm from the electronic balance. The weights were found to be in between
(tip of the tail). The duration of immobility was recorded 26.160.66 to 52.260.44 mg. The results are shown in the
for a time period of 5 min. Mice were considered Table4, 5 & 6.
immobile when they hung passively and completely
motionless for at least 1 min. The thickness of the prepared transdermal films was
determined by micrometer screw gauge. The thickness of
2.4.3.2. Skin irritation studies15 the transdermal films was found to be directly proportional
to the polymeric concentration. The thickness of the
The skin irritation test was performed on six healthy albino transdermal films varied between 0.180.01 to 0.360.4
rabbits weighing between 2.0 to 3.5 kg. Aqueous solution mm. The results are shown in the Table 4, 5 & 6.
of formalin 0.8% was used as standard irritant. Drug free
2 The folding endurance of a film is frequently used to
polymeric patches of 20 cm were used as test patches. estimate the ability of the film to withstand repeated
0.8% 0f formalin is applied on the left dorsal surface of bending, the folding endurance for transdermal films was
each rabbit, whereas the test patches was placed on found in the range of 98 to 217. Table 4, 5 & 6.
identical site, on the right dorsal surface of the rabbit. The
patches were removed after a period of 24 hrs with the
The percentage moisture absorption and percentage
help of alcohol swab. The skin was examined for
moisture loss test was carried out to check physical stability
erythma /edema.
or integrity of the film at humid condition. Among all the
formulations, containing PVA as a polymer showed
16
2.5. Data Analysis maximum moisture absorption 12.740.21% the
formulations containing HPMC and MC 12.640.19 and
The cumulative amount of drug permating per unit area 12.680.10 respectively. The relatively high moisture
versus time was plotted. The slope of the linear portion of absorption by hydrophilic nature of PVA then compared to
2 HPMC and MC. Percentage moisture loss from prepared
the plot was calculated as the flux (g/cm /hr.). For
films, the formulations containing MC showed maximum
precisely analyzing the skin permeation of selegiline
moisture loss (12.560.21) when compared to the
hydrochloride, the time course of skin permeation of drug
formulations containing HPMC and PVA (12.530.07 and
across a freshly excised rat abdominal skin was studied
12.370.10). This was due to less hydrophilic nature of
using Franz diffusion cell. Pure selegiline hydrochloride
methyl cellulose compared to the formulations containing
(without the mediation of an organic solvent or drug
HPMC and PVA which leads to the moisture loss. The
delivery system) was used in this investigation. For the
values are shown in Table 4, 5 & 6.
comparison between two groups of data .Significance eas
determined by student t-test were considered significant at
The drug content in all the formulations was found to be in
p <0.05.
between 93.400.27% (F13) to 97.250.55% (F12). The
results showed that, the drug content was uniform and

ISSN No: - 2456 2165
reproducible in each batch of different transdermal film menthol and eucalyptol were used. All the three permeation
formulations. The results of the drug content are shown in enhancers were used at 5% of polymer concentration in
Table 4, 5 & 6. all the formulations prepared. The release of selegiline
hydrochloride from HPMC transdermal patches with
Tensile strength of the film was determined to measure the permeation enhancers and EC as rate controlling membrane
ability of a patch to withstand rupture. As the ratio of was as follows: F4 (d-limonene) - 91.23%, F5 (menthol) -
concentration of drug :polymer is increased tensile strength 94.85% and F6 (eucalyptol) - 97.45% in 24 hrs. Fig.9.
also increased so tensile strength of transdermal film PVA transdermal films with permeation enhancers and EC
prepared by HPMC, PVA and MC. gave in the range of 0.30 as rate controlling membrane released the drug as follows:
2 F10 (d- limonene) - 93.71%, F11 (menthol) - 95.84% and
0.0 to 0.51 0.0 kg/mm . Addition of permeation
F12 (eucalyptol) - 98.27% in 24 hrs (Fig. 10). MC
enhancers did not have any effect on the tensile strength of transdermal films showed the in vitro release as follows:
the films. The results are shown in Table 4, 5 & 6. F16 (d- limonene) - 89.57%, F17 (menthol) - 92.57% and
F18 (eucalyptol) 94.85%. The results are shown in the Fig.
3.1 In- vitro release study 11. From the above results it can be observed that Selegiline
hydrochloride transdermal films prepared with PVA using
Transdermal films prepared by taking different drug: permeation enhancers showed highest release profile
polymer ratio such as 1:1, 1:2 and 1:3 (by making use of compared to HPMC and MC films. This in vitro release
drug reservoir polymers like HPMC, PVA and MC) and EC nature of PVA films can be attributed to hydrophilic
(2% of polymer concentration) as rate limiting membrane character of PVA resulting in more affinity towards water
were analyzed for in vitro release studies. The formulations and hence an increased thermodynamic activity of drug in
F1, F7 and F13 (drug: polymer ratio 1:1) containing HPMC, the films. The higher hydrophilic character of PVA,
PVA and MC as polymers released 93.20, 95.19 and compared to HPMC and MC is also supported by %
92.68% of drug respectively, for a period of 12 hrs (Fig. 1, 2 moisture absorption studies of the films. When the release
& 3). Similarly formulations F2, F8 and F14 (drug: polymer profile of HPMC, PVA and MC transdermal films based
ratio 1:2) containing HPMC, PVA and MC as polymers with different permeation enhancers was observed, it was
released 95.37, 96.79 and 95.37% of drug respectively, for a evident that eucalyptol polymeric films released maximum
period of 20 hrs (Fig. 1, 2 & 3). The drug release from the amount of drug (Fig. 4). Eucalyptol based formulations F6,
formulations prepared using drug: polymer ratios i.e., 1:1 F12 and F18 released 97.45, 98.27 and 94.85% of drug in
and 1:2 were for a period of 12 and 20 hrs, for all the three 24 hrs, whereas d-limonene formulations F4, F10 and F16
polymers used. To get once-a-day formulation for selegiline released 91.23, 93.71 and 89.57% of drug. Menthol based
hydrochloride another drug: polymer ratio 1:3 was used. formulations F5, F11 and F17 released 94.85, 95.84 and
Formulations F3, F9 and F15 containing HPMC, PVA and 92.57% of drug in 24 hrs. Fig. 13. Among all the
MC as polymers were prepared and they released 88.11, formulations prepared with penetration enhancers, PVA -
90.08 and 86.77% of drug for a period of 24 hrs (Fig. 1, 2 & selegiline hydrochloride film containing eucalyptol i.e., F12
3). As it can be observed from the release studies, released 98.27% of drug in a period of 24 hrs which was
formulations obtained from 1:3 ratio controlled the release maximum release compared to other films. This formulation
of drug for more extent compared to 1:2 or 1:1 ratio. This was selected as optimized one and was used for in vitro
was also supported by the thickness of films. The thickness permeation studies using excised rat abdominal skin (Fig.
of films increased with an increase in polymer concentration 5).
thereby controlling the release of drug for longer period of
time. Formulations F3, F9 and F15 (with 1:3 drug: polymer
3.2 In vitro permeation study using rat abdominalskin
ratio) containing HPMC, PVA and MC as drug reservoir
polymers were selected for further studies to know the effect
The permeation of selegiline hydrochloride across the rat
of permeation enhancers on the drug release. Since the main
abdominal skin was investigated using formulation F12 in
barrier or rate limiting step in transdermal drug delivery of
Franz diffusion cell. 97.08% of drug permeated through
polar, water soluble drugs is the lipophilic part of stratum
the film in 24 hrs. The reduced permeation of the drug
corneum, in which lipids (ceramides) are arranged in the
through rat skin compared to in vitro release in cellophane
form of a bilayer. Ceramides (specially ceramides 2 and
(Fig. 6) may be due to the skin structure having startum
ceramides 5, which are abundantly present in stratum
corneum, in which ceramides are arranged in the form of a
corneum) are tightly packed in the bilayer due to the high
bilayer which leads to slower permeation.
degree of hydrogen bonding. When, skin is treated with
terpenes, the existing network of hydrogen bonds between
3.3 In vitro permeation study (data analysis)
ceramides may get loosened because of competitive
hydrogen bonding. The hydrogen bond network at the head
The release flux of selegiline hydrochloride from different
of ceramides breaks as terpenes (e.g. terpineol) enter into
the lipid bilayer of stratum corneum. Since alcoholic OH transdermal films prepared was calculated and is given in
group can accept or donate the H bond, it leads to Table. For PVA films flux values were 0.114, 0.052 and
disruption of exiting hydrogen bonding between ceramides 2
0.039 g/cm /hr for 1:1, 1:2 and 1:3 drug: polymer ratios,
head groups, thereby facilitating the permeation of drug. In indicating flux decreased with increase in polymer
the present study three permeation enhancers d-limonene, concentration and thickness of the films. The same was

ISSN No: - 2456 2165
observed with HPMC and MC films. In case of transdermal

films prepared using different permeation enhancers, highest Interaction between drug and formulation was studied using
release flux was observed with eucalyptol based PVA film FTIR analysis. The FTIR spectrum revealed that there were
2 no interaction between drug and excipients [Figure 7 a,
F12 i.e., 0.042 g/cm /hr compared to HPMC and MC
b,c,d]. DSC thermograms observations shows the nature of
films. It was concluded that films with eucalyptol had
the endothermic peaks and their corresponding values
higher flux compared to d- limonene and menthol based
indicating the formulations SH, SH +PVA (F6 Drug:
films.
polymer ratio 1:3) similar to the reported literature. These
For precisely analyzing the skin permeation kinetics of
values indicate that there is no interaction of the drug with
selegiline hydrochloride transdermal films, the time course
the polymer and various excipients used for the study as
for the permeation of pure drug across excised rat
shown in [figure 8 a, b]. Thus like FTIR spectra DSC
abdominal skin was done. Pure selegiline hydrochloride
thermo grams also support the fact that no interaction of the
penetrated through the rat abdominal skin at a first order
drug with the polymers in the formulations prepared.
2
rate of 0.131g/cm /hr for a period of 8 hrs. The
2 IV. CONCLUSION
releasefluxofoptimizedformulationF12(0.042g/cm /hr)was
31%slowerthan that by pure drug, indicating the role of rate
controlling polymers in controlling the release of the drug Various batches of Selegiline hydrochloride transdermal
from the films. films were prepared using solvent casting method and
evaluated. Reservoir type transdermal films (formulation
3.4 In vivo studies F12) consisting of 5% eucalyptol satisfied all the
pharmaceutical parameters of transdermal films and
3.4.1 Anti-depressant activity showed the highest percent of drug release in controlled
manner over the period of 24 hrs. The said promising
formulation would be able to offer benefits such as
To find out the efficacy of drug in controlling deperssion,
increase permeation of drug, prolonged drug release,
anti-depressant activity for the formulation F12 was
reduction in frequency of administration and thereby may
evaluated using Tail suspension method. The data was
help to improve the patient compliance with the limitation
analysed by using paired-t test. Formulation F12 showed a
that formulation is non-erodible. Further work may be
highly significant anti- depressant activity with P<0.01.
carried out to establish the therapeutic utility of this system
by pharmacokinetic and pharmaco dynamic studies in
3.4.2 Skin irritation studies
human beings.
Skin irritation study was performed to determine whether ACKNOWLEDGEMENT
the developed transdermal film might cause irritation and
pain, after its application on the skin. The skin irritation The authors are grateful to Embio Limited, Mumbai for
study was performed by applying the sterile optimized providing gift sample of Selegiline hydrochloride. The
transdermal film F 12 on the skin of Swiss albino rabbits. authors would like to acknowledge the management, N.E.T
No signs of redness or erythma were observed up to 24 hrs Pharmacy College, Raichur, India for providing facilities
after application of the transdermal film (Fig. 9 a,b). Thus it during research.
was concluded that the formulation remained nonirritant to
rabbitskin.
3.5 Mechanism of drug release
The release kinetics of the transdermal films followed first

order and Higuchis diffusion kinetics. According to the first
order, the release of drug is based on the concentration of
the drug in the formulation. Further as per Higuchi release
kinetics, the drug release follows diffusion mechanism.
Percentage of drug released when plotted against square
root of time, the plots showed high linearity. It indicated
that release pattern followed Higuchis diffusion mechanism
which indicates that as the time increases, the diffusion path
length also increases.
Stability studies showed that, there is no significant change

in physical characteristics and drug content. Based on these
results it was concluded that the formulated transdermal
films were found to be physically and chemically stable
during the study period (30 days). Hence, the films were
found to be compatible with the skin.

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Table 1: Composition of Selegiline hydrochloride transdermal films by using HPMC

Plasticizer Rate
Drug Reservoir Permeation Enhancers (30% of Limiting
(5% of Polymer) Polymer) Membrane
Formulation
Code Terpenes (ml)
Selegiline HPMC Ratio Glycerine Ethyl
hydrochloride (mg) (ml) Cellulose
(mg) (%)
d-limonene
Menthol eucalyptol
F1 63 63 1:1 - - - 0.0150 2
F2 63 126 1:2 - - - 0.0150 2
F3 63 189 1:3 - - - 0.0150 2
F4 63 189 1:3 0.0037 - - 0.0150 2
F5 63 189 1:3 - 0.0035 - 0.0150 2
F6 63 189 1:3 - - 0.0034 0.0150 2
Casting Water (2.5 ml) Chloroform
Solvent
Table 2: Composition of Selegiline hydrochloride transdermal films by using PVA
Plastici Rate
Drug Reservoir Permeation Enhancers zer (30% Limiting
(5% of Polymer) ofPolyme Membra
Formulat
r) ne
ion Code
Terpenes (ml)
Selegiline PV Rati Glyceri Ethyl
d-
hydrochlor A o Menth eucalyp ne (ml) Cellulos
limone
ide (mg) ol tol e (%)
ne
(m
g)
F7 63 63 1:1 - - - 0.0150 2
F8 63 126 1:2 - - - 0.0150 2
F9 63 189 1:3 - - - 0.0150 2
F10 63 189 1:3 0.0037 - - 0.0150 2
F11 63 189 1:3 - 0.003 - 0.0150 2
5
F12 63 189 1:3 - - 0.0034 0.0150 2
Casting Water (2.5 ml) Chlorofo
Solvent rm

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Table 3: Composition of Selegiline hydrochloride transdermal films by using MC

Plastici Rate
Drug Reservoir Permeation Enhancers zer (30% Limiting
(5% of Polymer) ofPolyme Membra
Formulat
r) ne
ion Code
Terpenes (ml)
Selegiline M Rati Glyceri Ethyl
hydrochlor C o ne (ml) Cellulos
d-
ide (mg) limone menth eucalyp e (%)
(m ne ol tol
g)
F13 63 63 1:1 - - - 0.0150 2

F14 63 126 1:2 - - - 0.0150 2
F15 63 189 1:3 - - - 0.0150 2
F16 63 189 1:3 0.0037 - - 0.0150 2
F17 63 189 1:3 - 0.003 - 0.0150 2
5
F18 63 189 1:3 - - 0.0034 0.0150 2
Casting Water (2.5 ml) Chlorofo
Solvent rm
Table 4: Physicochemical evaluation of Selegiline hydrochloride - HPMC transdermal films

Formulation Weight Thickness % % Folding Tensile % Drug
code variation (mm) Moisture Moisture endurance strength content
(mg) Loss Absorption 2
(Kg/mm )
F1 27.140.44 0.230.001 12.730.18 12.360.18 98 94.500.27 94.50.27
F2 36.190.39 0.290.01 12.600.13 12.550.19 131 94.050.22 94.050.22
F3 47.850.45 0.360.09 12.550.20 12.630.09 189 95.320.32 95.320.32
F4 51.550.45 0.350.01 12.420.19 12.670.19 188 95.050.22 95.050.22
F5 51.670.43 0.360.02 12.490.09 12.670.08 195 95.600.04 95.600.04
F6 52.260.44 0.360.01 12.530.07 12.640.19 193 95.150.27 950.150.27
Average of three determinations SD

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Table 5: Physicochemical evaluation of Selegiline hydrochloride - PVA transdermal films

(mg) loss absorption 2
(Kg/mm )
F7 26.80.49 0.180.01 12.680.37 12.490.18 105 0.470.06 95.870.17
F8 35.760.44 0.200.01 12.600.28 12.600.28 161 0.490.02 96.150.28
F9 45.200.40 0.220.01 12.490.11 12.720.11 210 0.500.05 96.700.10
F10 47.170.55 0.210.01 12.420.10 12.780.10 208 0.490.03 96.420.23
F11 48.510.58 0.220.01 12.470.10 12.780.20 213 0.510.01 96.700.27
F12 48.900.5 0.220.01 12.370.10 12.740.21 217 0.510.02 97.250.55
Table 6: Physicochemical evaluation of Selegiline hydrochloride - MC transdermal films

(mg) Loss Absorption 2
(Kg/mm )
F13 26.160.66 0.200.02 12.830.10 12.260.19 101 0.430.05 93.400.27
F14 35.140.36 0.230.01 12.670.14 12.390.14 151 0.450.03 93.950.28
F15 42.790.39 0.280.01 12.640.23 12.520.11 191 0.460.01 94.050.22
F16 45.020.33 0.280.02 12.470.10 12.620.11 190 0.460.02 94.950.20
F17 45.460.36 0.280.01 12.550.22 12.530.22 195 0.460.05 95.050.10
F18 46.170.43 0.280.02 12.560.21 12.600.10 195 0.460.09 95.100.12

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Table No. 7 In vitro permeation of Selegiline hydrochloride transdermal film
Formulation Flux Cumulative

code 2 percentage of
(g/cm /hr)
drugpermeated
F1 0.107 93.20
F2 0.051 95.37
F3 0.038 88.11
F4 0.039 91.23
F5 0.040 94.85
F6 0.041 97.45
F7 0.114 95.19
F8 0.052 96.79
F9 0.039 90.08
F10 0.040 93.71
F11 0.041 95.84
F12 0.042 98.27
F13 0.110 92.68
F14 0.052 95.37
F15 0.037 86.77
F16 0.036 89.57
F17 0.040 92.570
F18 0.040 94.85
Fig. 1: In vitro release profile of Selegiline hydrochloride - HPMC transdermal films

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Fig. 2: In vitro release profile of Selegiline hydrochloride - PVA transdermal films

Fig. 3: In vitro release profile of Selegiline hydrochloride - MC transdermal films
Fig. 4: Effect of different permeation enhancers on Selegiline hydrochloride release profile
HD- HPMC:d-limonene, HM- HPMC:menthol, HE-HPMC:eucalyptol, PD- PVA:d-limonene, PM- PVA: menthol, PE-
PVA: eucalyptol, MD- MC d- limonene, MM- MC: menthol, ME- MC: eucalyptol

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Fig. 5: Comparison of in vitro release profile of Selegiline hydrochloride eucalyptol oil transdermal films
Fig. 6: In vitro release and in vitro permeation profile of Selegiline hydrochloride optimized transdermal film
IVP In vitro permeation, IVR - In vitro release

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Fig 7: IR spectra
Fig 8: DSC thermogram

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Skin irritation:
Figure : 9 a)Photograph showing rabbit with applied transdermal film
Figure: 9 b) Photograph of rabbit showing no signs of redness or erythma after removal of the film after 24 hrs

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Development and Evaluations of Transdermal Delivery of Selegiline Hydrochloride

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Volume 2, Issue 6, June 2017 International Journal of Innovative Science and Research Technology

ISSN No: - 2456 2165