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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

ISSN: 0975-7538
Research Article
www.ijrps.pharmascope.org

Preparation and evaluation of Transdermal patches of

Papaverine hydrochloride
Prabhu Prabhakara*, Marina Koland, Vijaynarayana K, Harish NM, Shankar G, Mohd Gulzar Ahmed,
Narayana Charyulu R, Satyanarayana D.

NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte Post, Mangalore, - 574 160 India

ABSTRACT

Transdermal patches of Papaverine hydrochloride were prepared by solvent casting method using ethyl cellulose:
PVP, PVA: PVP and eudragit RL-100: eudragit RS-100 in different ratios. The physicochemical parameters like flex-
ibility, thickness, smoothness, weight variation, moisture content, hardness and tensile strength were evaluated
and found to be flexible, uniform thickness and weight, smooth, good drug content (92 to 96%) and little moisture
absorption. The in-vitro diffusion studies were carried out using modified Keshery-Chein cell with cellophane as
diffusion membrane and the formulation followed Higuchi diffusion mechanism. The formulation containing
PVA:PVP as polymers showed faster release rate (hydrophilic polymers) compared to eudragit RL-100:eudragit RS-
100 (hydrophobic polymers) or combination of hydrophilic and hydrophobic polymers (Ethyl cellulose and PVP).
The stability studies indicated that all the patches maintained good physicochemical properties and drug content
after storing the patches in different storage conditions. Compatibility studies indicated that there was no interac-
tion between the drug and polymers. In vivo studies showed that papaverine hydrochloride helps in decreasing the effect
of isoproterenol induced myocardial necrosis.
Key words: Transdermal patch; Papaverine HCl; in-vivo study; ethyl cellulose; eudragit polymers.
INTRODUCTION delivery systems for clinical use (Scopolamine, Nitroglyce-
rine, Clonidine, Estradiol, Nicotine, Isosorbide dinitrate,
The goal of pharmaceutical research is to find drugs
Norethristerone acetate, etc.), which established the
with desirable therapeutic and low risk of undesirable
dermal route for systemic drug delivery (Udupa N,
side effects. Recent research and development efforts
Shaila lewis, Pandey S, 2006). Papaverine is an alkaloid
have been channelized into the development of drug
present in opium. It belongs to the group of medicines
delivery systems for controlled drug administration
called the vasodilator. It has direct relaxant action on
through various routes (or parts) of administration, for
smooth muscle, which is attributed in part to its ability
example, the skin, to maximize the bioavailability, to
to inhibit phosphodiesterases. It has been given in the
optimize the therapeutic efficacy, and/or minimize the side
management of cerebral, peripheral and coronary dis-
effects of the drug. In this system (transdermal drug de-
orders. The biological half life of papaverine HCl given
livery), the drug reservoir is encapsulated in a com-
by oral route is reported to be between 1-2 h. It shows
partment molded from a drug impermeable backing
less solubility in intestine pH. Papaverine HCl is rapidly
layer and a rate controlling polymeric membrane. In
absorbed orally and undergoes extensive first pass me-
the drug reservoir compartment, the drug particles are
tabolism in the gut wall and liver and the bioavailability
either dispersed or suspended in the solid polymer ma-
is as low as 30%. For the prolonged duration of action,
trix. It is anticipated that transdermal drug delivery system
sustained formulation is required because of low bio-
can be designed to input drugs at appropriate rates to
logical half life (Lloyd E, Matheson Jr., 1979). Hence, to
maintain a suitable plasma-drug level for therapeutic
improve its therapeutic efficacy, patient compliance
efficacy, without the periodic sojourns into the plasma
and to reduce the frequency of dosing and side effects,
concentration that would accompany toxicity or lack
as well as to avoid its extensive first pass metabolism,
of efficacy (Chein YW, 1987). Till date, various drugs
transdermal drug delivery approach was considered to
have been successfully incorporated into transdermal drug
be better suitable for papaverine hydrochloride. In view
of the above facts, in the present investigation, an
* Corresponding Author attempt is made to develop matrix type transdermal
Email: [email protected] patches of papaverine hydrochloride using suitable poly-
Contact: +91- 9448156797 Fax: +91-8242203992
mers like polyvinyl alcohol, polyvinylpyrrolidone, ethyl cellu-
Received on: 26-03-2010
Revised on: 09-05-2010
lose, eudragit RL-100 and eudragit RS-100.
Accepted on: 12-05-2010

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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

Table 1: Composition of Formulations

Ethyl Eudrgit Eudrgit

Formulation PVP PVA Drug
Cellulose RL-100 RS-100
Code (mg) (mg) (mg)
(mg) (mg) (mg)
F1 100 - 400 - - 150
F2 200 - 300 - - 150
F3 167 333 - - - 150
F4 250 250 - - - 150
F5 - - - 125 125 150
F6 - - - 100 250 150

Table 2: Physicochemical properties of the prepared Transdermal patches

*Tensile Percentage drug

Formulation *Hardness *%Moisture *Thickness
*%Elongation strength content in
code (kg) absorption (mm)
(kg/mm) 1 cm2
F1 0.326 ± 0.024 2.91 0.320 ±. 021 78.10 ± 08.12 0.416 ±0.051 93.24 ± 0.5127
F2 0.306 ± 0.012 3.14 0.328 ±. 016 82.40 ± 10.31 0.439 ±0.047 95.40 ± 0.5714
F3 0.386 ± 0.021 5.26 0.321 ± .028 89.70 ± 09.41 0.493 ±0.078 92.88 ± 0.4015
F4 0.419 ± 0.018 5.17 0.332 ±. 023 85.70 ± 07.85 0.452 ±0.063 95.04 ± 0.7481
F5 0.396 ± 0.028 3.20 0.249 ±. 071 91.20 ± 08.34 0.545 ±0.022 93.02 ± 0.5104
F6 0.418 ± 0.031 3.50 0.260 ±. 062 90.70 ± 10.94 0.520 ±0.035 93.60 ± 0.7345
MATERIALS For PVA and PVP Polymers (F3 and F4)
Papaverine hydrochloride was gift sample from Biologi- The casting solutions were prepared by dissolving
cal E.Ltd., Hyderabad. Polyvinyl alcohol (PVA) was ob- weighed quantities (Table 1) of polymers in water by
tained from LDH Laboratory Reagents, Mumbai, poly- heating on water bath. The drug was dissolved in dis-
vinyl pyrrolidone (PVP) was procured from Ozone In- tilled water and added to the above polymer solution
ternational, Mumbai and ethyl cellulose was procured along with propylene glycol (0.1 ml), as plasticizer, and
from Sulab Reagent, Mumbai. The other chemicals 0.1 ml of DMSO as penetration enhancer which is tho-
used in the study were of AR grade. roughly mixed to form a homogeneous mixture. The
volume was made up to 10 ml with water. En-
ANALYSIS
trapped air bubbles were removed by applying va-
Samples were analyzed by UV-visible spectrophotome- cuum.
ter (Jasco V-530) for the drug content.
For Eudragit RL-100 and Eudragit RL-100 (F5 and F6)
METHODS
The casting solutions were prepared by dissolving
Formulation of Transdermal Patches weighed quantities (Table 1) of polymers in etha-
nol:acetone (6:4). The drug was dissolved in chloro-
In the present study, matrix type transdermal patches
form and added to the above polymer solution along
of papaverine HCl were prepared by molding tech-
with propylene glycol, propylene glycol (0.1 ml), as
nique. A flat square shaped, aluminium foil coated
plasticizer, and 0.1 ml of DMSO as penetration enhanc-
glass molds having surface area of 25 cm2 were fabri-
er which is thoroughly mixed to form a homogeneous
cated for casting the patches.
mixture. The volume was made up to 10 ml with
Preparation of casting solutions ethanol. Entrapped air bubbles were removed by
applying vacuum.
For Ethyl cellulose and PVP (F1 and F2)
Preparation of Transdermal Patches
The casting solutions were prepared by dissolving
weighed quantities (Table 1) of polymers in chloro- The casting solution (10 ml) was poured into glass
form. The drug was dissolved in chloroform and added moulds and dried at room temperature for 24 h for
to the above polymer solution along with propylene solvent evaporation. The patches were removed by
glycol, propylene glycol (0.1 ml), as plasticizer, and 0.1 peeling and cut into square dimension of 3 cm x 3 cm
ml of DMSO as penetration enhancer which is tho- (9 cm2). These patches were kept in dessicator for 2
roughly mixed to form a homogeneous mixture. The days for further drying and wrapped in aluminium
volume was made up to 10 ml with chloroform. En- foil, packed in self-sealing covers. Transdermal
trapped air bubbles were removed by applying vacuum. patches were prepared with different polymer ratio,
with constant plasticizer concentration and permeation
enhancers (Saxena M et al., 2006).
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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

Evaluation of physicochemical properties were again weighed and % moisture absorption was
calculated (Das MK et al., 2006).
All the transdermal patches were visually inspected for
colour, flexibility, homogenecity and smoothness. The Drug Content Uniformity
thickness of the patches was measured at five differ-
Drug content estimation was carried out in triplicates
ent places on a single patch of each formulation using a
on each formulation. Each patch from different formu-
screw gauge and the mean values were calculated (Pra- 2
lations (patch size of 1 cm , equivalent to 6 mg of
shant M et al., 2005). Weight variation between the
drug)) was transferred into a graduated flask and
formulated patches can lead to a difference in drug
phosphate buffer pH 6.8 was added up to 100 ml mark
content and hence in vitro release behavior. A set of
for extracting the drug from the patch. The flask was
three patches from each batch having a diameter of
2 shaken for 4 h in a mechanical shaker. After extraction
1 cm were weighed on a digital balance and the
of the drug, the solution was filtered and diluted
mean values were calculated. The folding endurance
suitably with phosphate buffer pH 6.8 and the ab-
is expressed as the number of folds (number of times
sorbance was measured at 249 nm, against the pla-
the film is folded at the same place) required to break
cebo patch solution as blank and the drug content was
the specimen or to develop visible cracks. This also
calculated (Murthy SN & Hiremath SR, 2001).
gives an indication of brittleness of the film. A strip
2
of 2 cm x 2 cm (4 cm ) was subjected to folding en- Compatibility Studies
durance by folding the patch at the same place repeat-
In the present study, compatibility studies were car-
edly several times until a visible crack was observed and
ried out to assess any incompatibility between the
the values were reported (Das MK et al., 2006).
drug and polymers. The FT-IR studies were performed
The mechanical properties (percentage elongation to check the compatibility with excipients. Spectra of
and tensile strength) were evaluated using Instron the pure drug and the formulated patch were taken
universal testing instrument (model F. 4026), Instron individually. This is to ensure that there is no incompa-
Ltd., Japan,) with a 5 Kg load cell. Tensile strength is tibility between the drug and the polymers and other
the maximum stress applied to a point at which the components with plasticizer and penetration enhancer.
film specimen breaks. Film strips in special dimen-
sion and free from air bubbles or physical imperfec-
tions were held between two clamps positioned at a
distance of 3 cm. During measurement, the strips were
pulled by the top clamps at a rate of 100 mm/min; the
force and elongation were measured when the film
broke. Results from film samples, which broke at and
not between the clamps, were not included in the
calculations. Measurements were run in triplicate for
each film.
To determine the hardness of the patches, an appara-
tus was designed in our laboratory to study the hard- Figure 1: FT-IR spectra of papaverine hydrochloride
ness of the films using the literature report. It con-
sists of a wooden stand of 11 cm height and top area
of 16 cm x 16 cm. A small pan was fixed horizontally
to one end of the 2 mm thick iron rod whose other end
is reduced to a sharp point. A hole of 0.2 cm was made
at the center of tip area of wooden stand, which was
supported on the pan rod. An electric circuit was de-
veloped through a 3 volt battery in such a way that the
bulb glows only when the circuit is completed through
the contact of a metal plate and sharp end of the rod.
The film was placed between the metal plate and
sharp end of the rod. The weights were gradually add-
Figure 2: FT-IR spectra of EC: PVP formulation
ed at an interval of 10 sec for the stabilization of the
force till the bulb was glow. The final weight was consi-
In vitro drug release studies
dered as a measure of hardness (Das MK et al., 2006).
In vitro drug release profiles were carried out by
Moisture absorption
using modified Keshery - Chein diffusion cell with
Films (1cm2) of each formulation were accurately cellophane membrane. The cellophane membrane
weighed and exposed to ambient atmospheric con- was soaked in 100 ml of phosphate buffer pH 7.4 for
ditions of temperature (avg. temp 34 °C) and humidi- overnight and then cut into pieces of 7 cm2 area. It was
ty (75%) for three days. After three days, the films mounted on the diffusion cell and equilibrated with re-
©Pharmascope Foundation | www.pharmascope.org 261
 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

ceptor fluid for 15 min and used for the drug release stu- parameters at regular intervals (0, 15, 30, 45 and 60
dies. The modified Keshery - Chein diffusion cell de- days).
signed and fabricated in our laboratory as per the litera-
Skin Irritancy Studies
ture (Das MK et al., 2006). The cell consists of two
compartments, the donor and the receptor compart- Patches were applied to the shaved skin on one side of
ment. The donor compartment was in contact with the back of rabbit and secured using adhesive tape. On
ambient conditions of the atmosphere. The receptor other back side of the rabbit, control patch (without
compartment was in contact with a solution in the drug) was secured in a similar way. The animal was
receptor compartment (phosphate buffer pH 6.8.) and observed for any sign of erythema or oedema for a pe-
the contents were stirred by a rod-shaped magnetic riod of 48 h.
2
bead driven by a magnetic stirrer. One patch of 1 cm
Effect of drug on Isoproterenol induced myocardial ne-
was placed in the donor compartment of the diffusion
crosis
cell. The receptor fluid (5 ml) was withdrawn at prede-
termined time intervals (0 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 Male wistar rats (8) weighing 150-200 g were considered
h, 16 h and 24 h) and replaced immediately with same for this study. They were divided into three groups (4 in
volume of phosphate buffer pH 6.8. The samples each group). Group 1 was first pretreated with the test
were analyzed for drug content at 249 nm using UV- drug by applying the transdermal patch of 0.9 cm2 con-
visible spectrophotometer after suitable dilution taining 5.4 mg of drug /200 g of animal (Ghosh MN,
with phosphate buffer pH 6.8. 1984). Group 2 were applied transdermal patch contain-
ing no drug, and group 3 was normal control did not re-
ceive any treatment (for comparison). After 6 h, other
than the normal control group, were injected with 8.5
mg/kg isoproterenol by subcutaneous route on two con-
secutive days. After 48 h of first isoproterenol adminis-
tration, the rats were sacrificed and autopsied. Blood
samples (0.5 ml) were withdrawn on both the days [(day
1, after 24 h of first dose of isoproterenol inj), and day 2,
after 48 h of first dose of isoproterenol inj] for Lactate
dehydrogenase enzyme estimation by Wroblewski and
La Due method (Wroblewski F and La Due JS, 1955). The
animal heart was removed from the retro orbital route
Figure 3: FT-IR spectra of PVA: PVP formulation and weighed, and frontal sections were embedded for
histological examination. The histological examination of
the hearts was undertaken to study the severity of infarc-
tion. Necrosis produced by ischemia reperfusion injury
was graded (Vogel HG & Vogel WF, 2002). After micro-
scopic examination, grades were given as follows: grade
0, no change; grade 1, focal interstitial response; grade 2,
focal lesions in many sections,consisting of mottled stain-
ing and fragmentation of muscle fibres; grade 3, conflu-
ent retrogressive lesions with hyaline necrosis and frag-
mentation of muscle fibres and sequestrating mucoid
oedema; grade 4, massive infarct with occasionally acute
aneurysm and mural thrombi. This study was conducted
after obtaining the Animal ethical clearance from Institu-
Figure 4: FT-IR spectra of eudragit RL-100: eudragit tional Animal Ethics Committee (K.S. Hegde Medical
RS-100formulation Academy).
Stability Studies Curve fitting analysis
To any rational design and evaluation of dosage In vitro drug release data were fitted to kinetic models
forms, the stability of the active component must be such as zero-order (Brazel & Peppas, 2000), first-order
major criterion in determining the acceptance or rejec- (Lapidus & Lordi, 1966), Higuchi equation (Higuchi,
tion. The stability studies of the formulated trans- 1963). Qt versus t (zero order), log Qt versus t (first
dermal patches were carried out on prepared films order), Qt versus square root of t (Higuchi), where Qt is
at different temperature and humidity 25-30°C the amount of drug released at time t. The criteria for
(60%RH) and 45-50°C (75%RH) over a period of 60 selecting the most appropriate model are highest R2
days. The patches were wrapped in aluminium foil and value as it indicates the linearity of dissolution data
stored in stability chamber for stability study. The (Thakkar et al., 2009).
patches were characterized for drug content and other

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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

RESULTS AND DISCUSSION ters. In the present study total six formulations were
prepared by varying polymer ratio, and by using different
Formulation of Transdermal Patches
polymers. These patches were subjected to evaluation of
Transdermal patches of Papaverine HCl were prepared various physicochemical characteristics and drug release
by casting method on glass moulds, using PVA, PVP, studies. Different formulations (F1, F2, F3, F4, F5 and
ethyl cellulose, eudragit RL-100 and eudragit RS-100 as F6) were prepared using PVA, PVP, ethyl cellulose, eu-
polymers, propylene glycol as plasticizer, DMSO as dragit RL-100 and eudragit RS-100 to study the effect of
penetration enhancer. Chloroform was used as sol- polymers at different ratios on the physicochemical
vent for EC: PVP and water was used as solvent for PVA: properties. Physical appearance of the patches was
PVP and mixture of ethanol: acetone (6:4) was used as evaluated. All the patches prepared with different
solvent for eudragit RL-100: eudragit RS-100. Effect of polymer concentration were found to be flexible, smooth,
concentration ratio of polymers and nature of poly- opaque, non sticky and homogeneous. Thickness of the
mers was studied by preparing various formulations of patches in each set was measured. Marginal differ-
transdermal patches. In the preparation, set-up addition ence in thickness was observed among each group
of ingredients particularly propylene glycol and DMSO was indicated that more the amount of polymer higher the
followed after careful evaluation of patches for physical thickness values (Table 2). All the six patches have
characteristics. In all these formulations a constant showed good folding endurance (75-100) indicated
amount of drug (150 mg) was maintained. The casting that the patches have good flexibility. Water absorption
solution (10 ml) was poured into 25 cm2 moulds, so studies revealed that as the concentration of PVP,
that each cm2 contains approximately 6 mg of drug. PVA, eudragit RS-100 (F2, F3, F6) increased the
Polymers were used in different ratios and the concen- amount of water absorption also increased. Among the
tration of other ingredients such as plasticizer and pene- patches, F3 (PVA: PVP ratio 2:1) absorbed higher mois-
tration enhancers were kept constant. ture content. This may be due to the hydrophilic nature
of the PVA and PVP. The least percentage of moisture
Evaluation of Transdermal Patches
absorption was observed for F-1 patch (EC: PVP) as com-
Transdermal patches of papaverine hydrochloride pared to other patches because of hydrophobic nature of
were formulated and evaluated for various parame- ethyl cellulose. The effect of concentration of polymers

Figure 5: Comparison of in vitro release profiles of formulations

Figure 6: Comparison of prolonged in vitro release profiles of F2, F3 and F5

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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

was observed on the percentage elongation and tensile Curve fitting analysis
strength. It was found that as the concentration of PVP
To know the mechanism of drug release from these
increased the percentage elongation and tensile
formulations, the data were treated according to first-
strength was also increased within the patches contain-
order, Higuchi’s and zero order pattern. The release
ing the combination of EC and PVP. Eudragit patches
kinetics of the transdermal patches followed first order
showed better tensile strength due to the nature of po-
(0.9456 – 0.9724) and Higuchi’s diffusion kinetics
lymers (Table 2). There was no significant difference in
(0.9755 – 0.9992). According to the first order the re-
the drug content among the patches indicated content
lease of drug is based on the concentration of the drug
uniformity. All the patches were found to be opaque,
in the formulation. Further as per Higuchi’s release
smooth, flexible and non-sticky in nature. This may be
kinetics; the drug release followed diffusion mechan-
due to the presence of plasticizer. It was observed that
ism. Percentage of drug released when plotted against
there was no significant difference in the thickness
square root of time, the plots showed high linearity. It
among the patches, indicated that the patches are
indicated that release pattern followed Higuchi’s diffu-
uniform.
sion mechanism which states that as the time increases the
Compatibility Study diffusion path length also increases.
The FT-IR spectra of pure drug, polymers and formula- Stability Studies
tions were carried out and represented as in Fig 1-4. The
Stability studies were carried out for 60 days at
principal peaks of pure drug papaverine hydrochloride 0
room temperature, temperature of 25- 30 C, 60%RH
were obtained at wave number 1602.90 cm-1, 1512.24 0
and 45- 5 0 C , 75% RH. The patches were observed
cm-1, 1026.16 cm-1, 1278.85 cm-1 which corresponds to
for physical change and drug content. It was found
the theoretical peaks at wave number 1598 cm-1, 1508
that, when the patches were stored at 25-
cm-1, 1026 cm-1, 1279 cm-1. The corresponding peaks of
300 C, 60%RH, the loss of drug was approximately 2-
pure drug were also present in transdermal formulations.
3% at the end of 60 days. However, the amount of
From the spectral studies, it was concluded that there
drug loss was found to be much higher (14-18%)
was no interaction between drug and polymers.
when stored at 45- 50°C, 75% RH. Further, the
In vitro drug release studies amount of drug loss was found to be more (18%)
from hydrophilic polymers (F3 & F4) compared to
In vitro drug release study was carried out using cello-
combination of hydrophilic and hydrophobic po-
phane membrane and modified keshery-chein diffusion
lymers or only hydrophobic polymers.
cell. It was observed that from hydrophilic polymers (F3
and F4) the drug release was found to be faster com- Skin Irritancy Study
pared to the combination of hydrophilic and hydro-
Results of skin irritancy study revealed that neither blank
phobic polymers (F1 & F2) or only hydrophobic poly-
patch nor patch containing papaverine hydrochloride
mers (F5& F6) used in the study (Fig 5). Patches pre-
caused any noticeable sign of erythema or oedema on
pared with PVP and EC as polymers, found that more the
rabbit skin throughout the period of 48 h. Hence the
amount of PVP better the drug release due to the hydro-
patches were found to be compatible with the skin.
philic nature of PVP. A significant change in drug release
was observed from patches containing more amount of Effect of drug on Isoproterenol induced myocardial ne-
PVA showed highest release (F3 compared to F4). This crosis
may be attributed to hydrophilic nature of the poly-
From the in vivo effect of drug on isoproterenol induced
mers which has more affinity for water results in in-
myocardial necrosis study, it was found that the LDH
creased thermodynamic activity of the drug in the film.
(Lactate dehydrogenase) level increased marginally in
Patches containing eudragit RL-100 and eudragit RS-100
rats treated with transdermal patch (404 IU/L) on day
(F5 and F6) showed slower release as the patches con-
one (after 24 h), and reduced to normal level of 280 IU/L
tains only hydrophobic polymers, which might have lead
after 48 h, compared to the group of animals which
to slower release of drug from the patches. Further the
were not treated with drug containing transdermal
drug release study (F2, F3, and F5) was when conducted
patch, where the level of LDH remained very high (717
for 40 h (Fig 6), it was observed that approximately 75-
IU/L) even after 48 h. The normal value for LDH is 100-
80% of drug was released. Hence transdermal patches
330 IU/L (Abraham N et al, 2006). Thus the extent of
can be used for extended period of time. The release profile
damage was found to be minimum in group of animals
was correlated with the moisture absorption which further
treated with transdermal patch containing papaverine
reflected by the nature of polymer.
HCl compared to the group of animals applied with pla-
From the above data, it can be concluded that the release cebo patch (without drug). The initial (in 24 h) rise in LDH
characteristics may be restricted to only in vitro release level in animals treated with drug containing transdermal
study, as the in vitro release model mainly favours the hy- patch was probably due to the slow absorption of the
drophilicity. However, when theses patches applied to the drug into the blood stream and hence sufficient amount
skin results may differ as the lipophilicity may play a major of drug was not present in the blood. However, the LDH
role for drug transport system. level reached to normal within 48 h indicates that the
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 Prabhakara et al. | Int. J. Res. Pharm. Sci. Vol-1, Issue-3, 259-266, 2010

transdermal patches can be used as controlled drug deli- ACKNOWLEDGEMENT

very system in the treatment of myocardial necrosis.
The authors are grateful to Nitte University, Manga-
Further, it was found that there was significant decrease
lore, NITK Suratkal and DR. Pathani Scintific & Industri-
in myocardial necrosis in rats applied with the transder-
al Research, Mumbai, for providing the necessary facili-
mal patch containing papaverine hydrochloride com-
ties to carry out this study.
pared to the group of animals not treated with trans-
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