Journal of Drug Delivery Science and Technology 45 (2018) 408–414

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Journal of Drug Delivery Science and Technology

journal homepage: www.elsevier.com/locate/jddst

Controlled delivery of rivastigmine using transdermal patch for effective T

management of alzheimer's disease
Mayank Kumar Malaiya, Ashish Jain, Hurkat Pooja, Anki Jain, Dharmendra Jain∗
Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, 470003, India

A R T I C LE I N FO A B S T R A C T

Keywords: Alzheimer's disease is a chronic neurodegenerative disease. Preparation of transdermal patches is a useful
Alzheimer's disease strategy for management of the disease. The transdermal patches bearing Rivastigmine tartarate were prepared
Rivastigmine using solvent casting method to provide good drug content uniformity. Transdermal patches were characterized
Transdermal patches for various attributions viz. patch weight, patch thickness, folding endurance, surface morphology study, X-Ray
Solvent casting method
diffraction study, Differential Scanning Calorimetry, tensile strength, surface pH, percent swelling, percent
Folding endurance
moisture sorption, drug content uniformity, In vitro release study, and ex-vivo study. Results of in vitro drug
release studies clearly indicate that the drug release governed polymer interaction. No lag time was observed
then reduction in drug release rate was observed. Extended drug release of 75.15 ± 1.43% within 24 h was
observed with formulation. The results of the permeation study indicated that the rate of drug permeation was
slow and it was found that 61 ± 1.43% of Rivastigmine tartrate could permeate through the skin membrane in
24 h. In the light of the above mentioned considerations, it is clear that the developed transdermal patch bearing
Rivastigmine tartrate was retained in skin layer and delivers the therapeutic amount of drug in blood for longer
time. This indicates the potential use of transdermal patches in the treatment of Alzheimer disease.

1. Introduction positron Emission Tomography (FDG-PET) measurements of decline in

Alzheimer's disease (AD) accounts for 60–70% of cases of dementia
[4]. It is a chronic neurodegenerative disease that usually starts slowly
and gets worse over time [8]. Alois Alzheimer recorded the first case of
Alzheimer's disease (AD) in 1906 [17]. The most common early
symptom is complexity in remembering recent events (short term
memory loss). As the disease advances, symptoms can include: pro-
blems with language, disorientation (including easily getting lost),
mood swings, loss of motivation, not managing self-care, and beha-
vioural issues [4]. As a person's condition declines they often withdraw
from family and society. Gradually, bodily functions are lost, ultimately
leading to death [20]. The pathophysiological hallmarks of AD include
extracellular β-amyloid protein (Aβ) deposition in the forms of senile
plaques and intracellular deposits of the microtubule-associated protein
tau as neurofibrillary tangles in the brain.
Presently, a definitive diagnosis of AD is possible only after death,
when the presence of plaques and neurofibrillary tangles in the brain
parenchyma can be revealed after pathological examination. The best
established measurements for the detection and tracking of AD include
cerebrospinal fluid (CSF) measures of Aβ and tau, structural magnetic
resonance imaging (MRI) of hippocampal atrophy, fluorodeoxyglucose
the metabolic rate of glucose, PET measurements of brain Aβ by
Pittsburgh Compound B (PIB) [23].
Scientists do not yet fully understand what causes AD, but it is clear
that it develops because of a complex series of events that take place in
the brain over a long period of time. It is likely that the causes include
genetic, environmental, and lifestyle factors. There is no cure for
Alzheimer's disease; available treatments offer relatively small symp-
tomatic benefit but remain palliative in nature. Current treatments can
be divided into pharmaceutical, psychosocial and care giving. Common
medications are only symptomatic and aim to restore the disrupted
neurotransmission between the degenerated neurons [16]. Current
therapies for AD include the Acetylcholinesterase inhibitors (Donepezil,
Galantamine and Rivastigmine), and a low-affinity NMDA (N-methyl-d-
aspartate) receptor antagonist (Memantine) for moderate to severe AD.
The acetylcholinesterase inhibitors mediate their effects by re-
mediating, in part, the cholinergic deficit in AD, whereas the precise
mechanism of action of memantine remains to be elucidated. Overall,
the effects of these drugs are limited as they modestly improve some of
the symptoms but do not treat the underlying causes of the disease [13].
At present, the most common form of delivery of drugs is the oral route.
While this has the notable advantage of easy administration, it also has

∗
Corresponding author. Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, 470003, India.
E-mail address: dharmjain@gmail.com (D. Jain).

https://doi.org/10.1016/j.jddst.2018.03.030
Received 2 August 2017; Received in revised form 17 November 2017; Accepted 25 March 2018
Available online 10 April 2018
1773-2247/ © 2018 Elsevier B.V. All rights reserved.
M.K. Malaiya et al.
significant drawbacks-namely poor bioavailability due to hepatic me-
tabolism (first pass) and the tendency to produce rapid blood level
spikes (both high and low), leading to a need for high and/or frequent
dosing, which can be both cost prohibitive and inconvenient.
Reduction in the activity of the cholinergic neurons is a well-known
feature of Alzheimer's disease [1]. Acetylcholinesterase inhibitors are
employed to reduce the rate at which acetylcholine (ACh) is broken
down, thereby increasing the concentration of ACh in the brain and
combating the loss of ACh caused by the death of cholinergic neurons
[2]. There is evidence for the efficacy of these medications in mild to
moderate Alzheimer's disease, [14, 15] and some evidence for their use
in the advanced stage.
The blood-brain barrier (BBB) is a common obstacle in treating CNS
diseases. The BBB represents such an insurmountable obstacle for most
drugs and contrast agents, an effective treatment or diagnosis of many
brain diseases is difficult or not possible. Therefore, a number of dif-
ferent strategies such as osmotic opening of the tight junctions, direct
surgical administration of molecules into the brain, and the use of
prodrugs or carrier systems interacting with specific transporters and/
or receptors expressed at the luminal (blood) side of the endothelial
cells employed during the past years to overcome this barrier [18,26].
Woo et al. [25] and Ravi & Gupta [22] also presented transdermal
patches as treatment option for Alzheimer's disease. To overcome the
limitations posed by BBB, transdermal patches can be used to deliver a
specific dose of medication through the skin into bloodstream. Trans-
dermal delivery provides controlled, constant administration of the
drug, and allows continuous input of drugs with short biological half-
lives and eliminates pulsed entry into systemic circulation [27].
Nausea, vomiting and diarrhoea are much less common side effects
with the patch than with the capsule and tablets. They provide ex-
tended therapy with a single application, improving compliance over
other dosage forms requiring more frequent dose administration. The
drug rivastigmine possess suitable characteristics for transdermal de-
livery such as low daily doses (1.5–6 mg twice daily), short half-life
(1.5 h), low molecular weight (400.43 gms). The rivastigmine patch
provides a viable treatment option for patients with mild to moderate
AD; it has an improved tolerability profile compared with rivastigmine
capsule doses providing comparable drug exposure and efficacy. This
has been mainly attributed to the favourable properties of lack of first
pass metabolism effects of liver, better patient compliance, steady re-
lease profile and lowered pill burden in transdermal system.
Therefore, it is envisaged that transdermal patches bearing
Rivastigmine can overcome most of demerits of conventional delivery
and will be able to release the drug at predetermined rate into systemic
circulation for a prolong period of time, thereby minimizing its adverse
effect and improving patient compliance.
The main components to a transdermal patch are polymer matrix,
drug, permeation enhancers, adhesive, backing laminates, release liner,
other excipients like plasticizers and solvents [28].
2. Materials and methods
2.1. Materials
The drug Rivastigmine tartrate was obtained as a gift sample from
Cipla limited, Mumbai India. Polyvinyl pyrolidone and Ethyl cellulose
(Central Drug House, Ltd), polyvinyl alcohol and Chloroform (Himedia
Laboratories), Dibutyl phthalate (Ranbaxy Laboratories Limited) was
obtained from Drug Delivery Research Laboratory, Department of
Pharmaceutical Sciences, Sagar. Other chemicals, solvents and reagents
were of analytical grade.
2.2. Methods
A transdermal patch used for targeting a drug to a particular region
of body for extended period of time is used to deliver a specific dose of
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Journal of Drug Delivery Science and Technology 45 (2018) 408–414
medication through the skin and into bloodstream. Transdermal patch
bearing Rivastigmine tartarate were prepared by solvent casting
method.
2.2.1. Preparation of backing membrane
The backing membrane was prepared using an aqueous solution of a
6% w/v of polyvinyl alcohol (PVA). Weighed amount of polyvinyl al-
cohol (600 mg) was added to a 10 ml of warm distilled water and was
constantly stirred on a magnetic stirrer at 60 °C for 5 min without for-
mation of bubbles to attain a homogeneous solution. Then 3 ml of
homogeneous solution was poured into a glass bangle placed on the
surface of aluminium foil in a Petridish. The rate of evaporation of the
solvent was controlled by inverting the funnel over the Petridish. Glass
spherical Petridish mold (1.4 cm depth, 5.2 cm internal diameter) to
one of the open end and circumference was wrapped by aluminum foil.
Smooth uniform, transparent backing membrane was obtained after
keeping the mold at 60 °C for 6 h [5,6].
2.2.2. Formation of drug matrix over the backing membrane
Blend of polymers polyvinyl pyrolidone (PVP) and ethyl cellulose
(EC) were measured in the requisite ratios of 1:2 and were dissolved in
5 ml of chloroform and a homogeneous solution was prepared using
magnetic stirrer. Then the plasticizer Dibutyl phthalate (DBP) and
Rivastigmine tartrate (100 mg) were added to the mixture and stirred
for 20 min until a homogeneous suspension was obtained. Then 5 ml of
the homogeneous suspension was casted on the prepared backing
membrane and dried at room temperature for 24 h, which yielded a
uniform, flat medicated matrix patch of Rivastigmine tartrate [7,10].
Formulation shows maximum water vapor transmission in 24 h i.e.
4.76 × 10−3 g/cm2 and it shows extended drug release i.e. 36 h.
3. Characterization of transdermal patches
3.1. Patch weight
For evaluation of patch weight three patches of each formulation
were taken and weighed individually and average weight was calcu-
lated.
3.2. Patch thickness
For evaluation of patch thickness, 3 patches of formulation were
taken and the patch thickness was measured using screw gauge of three
different places and the mean thickness of patches was calculated.
3.3. Surface morphology (SEM)
Scanning Electron Microscope (SEM) was used as visualizing aid for
surface morphology. The patches were mounted on an aluminium
sample support by means of a conductive and double sided adhesive
tape. The morphologies of the patch surfaces analyzed using a Philips
XL30 TMP SEM (LEO 435 UP, Eindhoven, The Netherlands) at an ac-
celeration voltage of 30 kV, the photomicrographs were taken at sui-
table magnification. The images were taken without the use of a metal
coating. Photomicrographs (Fig. 1) shows the SEM image of the patch.
3.4. X- ray diffraction pattern (X-RD study)
X-ray diffraction study was carried on pure drug and transdermal
patch containing drug using the XRD technique (model X'Pert-the
Netherlands). XRD study was performed on the samples by expose them
to Cu K-α-1 radiation (45 kV, 40 mA) and scanned from 2 to 50° 2θ, at a
step size of 0.0170 2θ and a step time of 20.0271 s. Fig. 2 shows the
XRD pattern of pure drug and transdermal patch.
M.K. Malaiya et al.
Fig. 1. (A) SEM images of transdermal film, (B) SEM image of after transdermal film after dissolution of 4 h.
3.5. Differential scanning calorimetry
The physicochemical compatibility between Rivastigmine and
polymers used in the patches was studied using differential scanning
calorimetry (Jupiter STA 449 F1 Nersch). In DSC analysis, the samples
were weighed (2 mg), hermetically sealed in flat-bottom aluminum
pans, and heated over a temperature range of 50–250 °C (in case of pure
drug) and 50–150 °C (in case of patch) in an atmosphere of nitrogen
(50 mL/min) at a constant increasing rate of 10 °C/min. The
Thermograms (Fig. 3) obtained for Rivastigmine and transdermal patch
and compared.
3.6. Folding endurance
The folding endurance is important to check the ability of sample to
withstand folding was measured manually for the prepared patches. It
is expressed as number of times the patch is folded at the same place
either to break the patch or to develop visible cracks. This also gives an
indication of brittleness [21]. This was determined by repeatedly
folding one patch at the same place till it break. The number of times
Fig. 2. X ray diffraction pattern of (A) Pure drug and (B) Drug loaded film.
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Journal of Drug Delivery Science and Technology 45 (2018) 408–414
the patch could be folded at the same place without breaking/cracking
gave the value of folding endurance [9].
3.7. Tensile strength
A tensile strength study for patch is total weight necessary to break
or rupture the patch and this was done by a device has rectangular
frame with two plates made up of Plexiglas's. The one plate is in front
and is movable part of device and can be pulled by loading weights on
the string, which is connected to movable part, the 2 × 1 cm2 plate. The
force needed to fracture the patch was determined by measuring the
total weight loaded in the string. The weight loaded corresponds to
break the patches were taken as tensile strength and the values are
given in Table 1. Following formula was used to calculate the me-
chanical properties of the patches.
Force of break(g)
Tensile Strength =
Initial cross sectional of the sample(cm2)
M.K. Malaiya et al. Journal of Drug Delivery Science and Technology 45 (2018) 408–414

Fig. 3. (A): Differential scanning calorimetry of pure drug Rivastigmine. (B) Differential scanning calorimetry of transdermal film.

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M.K. Malaiya et al. Journal of Drug Delivery Science and Technology 45 (2018) 408–414

Table 1
Evaluation of transdermal patches. 6 Percent moisture sorpƟon
Parameters Observation 5

Percent moisture sorpƟon

4
Film Weight (mg) 35.23 ± 0.19
Thickness (mm) 00.38 ± 0.01 3
Folding Endurance 276 ± 08 2
Tensile strength (gcm−2) 287 ± 1.8
Surface pH 5.4 ± 0.08 1
Drug content uniformity (%) 95.87 ± 2.3 0
1 2 3
N = 3, Mean ± SD. Time (In days)

3.8. Surface pH Fig. 5. Percent moisture sorption of different transdermal patches (n = 3).

Normally skin pH is around 5.8. Surface pH of the patches was

determined by the method described by Ref. [3]. The patches were
allowed to swell by keeping them in contact with phosphate buffer
(pH5.8) for 2 h in glass tubes at room temperature. The surface pH was
then noted by bringing a combined glass electrode near the surface of
the patch and allowing it to equilibrate for 1 min.
3.9. Swelling
Three patches of formulation was allowed to swell on the surface of
agar plate kept in an incubator at 37 ± 0.2ᵒC. Increase in weight of the
patch (n = 3) was determined at every hour upto 6 h. The percent
swelling was calculated using the following equation:
3.11. Drug content uniformity
From the prepared drug contained patches specified surface area
(1 cm2) were cut and dissolved in 100 ml of pH 7.4 phosphate buffer,
and vigorously shaken for 2hrs, and then centrifuged at 5000 rpm for
30 min. Then the drug contained polymeric solution was filtered
through 42 number whatman filter paper, and drug content was de-
termined at ƛmax 264 nm using double beam UV–Visible spectro-
photometer (Shimadzu 1601, Japan). Respected Placebo patch was
taken as blank solution preparation and results in reported in Table 1.
3.12. In vitro drug release study

Wt − Wo In vitro drug release study is a prerequisite for evaluating the In vivo

Percent Swelling =
Wo performance of a drug delivery system because the in vitro drug release
where, Wt is the weight of the swollen patch after time t, and Wo is the profile provides the most sensitive and reliable information for in vivo
initial patch weight at zero time (The mean values of three readings are evaluation that helps in ascertaining the future behaviour of the de-
calculated and reported in Fig. 4). signed formulation with regards to its drug release pattern and the time
duration of its action in a biological system.
3.10. Percent moisture sorption The in vitro release was carried out with the dialysis membrane
using Franz diffusion cell (Fig. 7). The cell consists of two chambers, the
Three patches (1 × 1cm size) were dried in the oven at 30 ± 2ᵒC. donor and the receptor compartment. The donor compartment was
After drying the weight of each patch was measured. The patches were open at the top and exposed to the atmosphere. The temperature was
successively transferred to desiccators over saturated salt solution of maintained at 37 ± 0.5 °C and receptor compartment was provided
sodium nitrite (75 ± 5% RH) at 25ᵒC. After each 1, 3, 5 days, the with sampling port. The diffusion medium used was PBS pH 7.4 solu-
conditioned patches were weighed and noted the weight and placed tion. The drug containing patch with a support of backing membrane
back to desiccators. Percentage moisture sorption was calculated using was kept in the donor compartment and it was separated from the re-
following formula: ceptor compartment by dialysis membrane. The dialysis membrane was
previously soaked for 24 h in PBS (pH 7.4). The donor and receptor
we − wc
Percentage moisture sorption = ×100 compartments were hold together using clamp. The receptor compart-
wc ment with 15 ml of PBS pH 7.4 was maintained at 37 ± 0.5 °C and
where, We = Weight of exposed patch, and Wc = Weight of conditioned stirred on magnetic stirrer, to prevent the formation of concentrated
patch. drug solution layer below the dialysis membrane. The release study was
The mean values of three readings are calculated and reported in performed for 24 h. After every 1 h, 1 ml samples were withdrawn from
Fig. 5. receptor compartment and immediately replaced with fresh media. The
withdrawn samples were filtered; 1 ml of the filtrate was diluted to
10 ml using PBS (pH 7.4). The samples were analyzed spectro-
Time Percent Swelling
photometrically at 264 nm. In vitro percentage cumulative release of
80 drug from transdermal patch formulation is shown in Fig. 6.
70
Percent swelling

60 3.13. Ex- vivo drug permeation studies

50
40 3.13.1. Preparation of excised goat skin
30 Goat skin was procured from the local slaughter house (Sagar). The
20 pouch was washed and rinsed with the normal saline to remove any
10 looser material from a pouch. A thin layer of mucosa of about 30 mm
0 diameter was stripped with the help of forceps. The mucosa was flat-
1 2 3 4 5 6
tened, kept in normal saline at refrigerated temperature overnight.
Time (in Hours)

3.13.2. Modified diffusion cell

Fig. 4. Percent swelling of transdermal patch (n = 3). For exvivo drug permeation study, a modified diffusion cell was

412
M.K. Malaiya et al.
Fig. 6. In vitro release profile of rivastigmine tartarate from transdermal patch.
Fig. 7. Franz diffusion cell.
used. It considered of an open-ended glass cylinder of approximate 4 cm
diameter and a beaker filled with 100 ml PBS (pH 7.4). The excised
mucosa was tied delicately on to one end of the glass cylinder. The
cylinder acts as donor compartment while the beaker act as a receptor
compartment. The glass cylinder was fixed vertically in the glass beaker
in such a way that the mucus membrane just baths the content of the
beaker. This assembly set up was placed over a magnetic stirrer with a
teflon bead inside the receptor compartment for constant stirring the
content of media and temperature of 37 ± 0.5ᵒ C was maintained
throughout the experiment.
The ex-vivo drug permeation study of transdermal patch through
excised goat buccal mucosa was studied using the modified diffusion
cell. A 1 × 1 cm size patch was placed intimate contact with the goat
buccal mucosa. The sample were withdrawn at every hour, filtered,
diluted suitably and then absorbance were taken. Ex-vivo percent cu-
mulate drugs permeated from formulation (Fig. 8).
4. Results and discussion
Solvent casting method was selected for the preparation because of
easy availability of the processing requirements in the laboratory,
economical scale up and good drug content uniformity.
Ethyl cellulose (EC), polyvinyl pyrolidone (PVP) and polyvinyl al-
cohol (PVA) were selected for the preparation of rivastigmine trans-
dermal patch because of Compatible with drug, economic, nonirritating
to skin and good patch forming capacity. Dibutyl phthalate was selected
as the plasticizer in the present study as it is economic with good
elasticity to make the patches. It also provides adhesiveness to the
patches.
Formulation showed4.76 × 10−3 g/cm2 maximum water vapor
413
Journal of Drug Delivery Science and Technology 45 (2018) 408–414
Fig. 8. Ex Vivo drug permeation profile of transdermal patch through goat
membrane (n = 3).
transmission in 24 h.
These transdermal patches were characterized for various attribu-
tions viz. patch weight, patch thickness, folding endurance, surface
morphology study, X-Ray diffraction study, Differential Scanning
Calorimetry (DSC), tensile strength, surface pH, percent swelling, per-
cent moisture sorption, drug content uniformity, In vitro release study,
and ex-vivo study.
The patch weight and thickness was found to be 35.23 ± 0.19 mg
and 00.38 ± 0.01 mm, respectively. The folding endurance measures
the ability of patch to withstand rupture. It was found to be 276 ± 08.
The folding endurance values of patches were found to be optimum and
therefore the patches exhibited good physical and mechanical proper-
ties. The result indicated that the patches would not break and maintain
their integrity with general skin folding when applied.
In order to examine the surface morphology, formulations were
examined under Scanning Electron Microscope (SEM). It was found that
the surface morphology of patch was smooth surface as shown by
photomicrographs (Fig. 1A). On keeping the patches in the dissolution
medium the pore were formed that are clearly seen in the SEM pho-
tograph of the patch after 240 min (Fig. 1B). The pore formation on
patch surface may be due to the dissolution of the hydrophilic polymer
of patch.
The X-ray diffraction gives us about the crystalline and amorphous
nature of the drug within the transdermal patches. The sharp peaks
present in diffractogram indicates crystalline of the compound which
were absent in case of amorphous compounds. In case of Fig. 2 both
(pure drug and transdermal patch) have the sharp peak so it indicates
that the drug is in crystalline state in the patch.
DSC studies were carried out for Rivastigmine tartarate pure drug
and its physical mixture form of transdermal patch. The DSC thermo-
gram (Fig. 3A and B) of drug showed an exothermic peak at 107.19 °C
corresponding to its melting temperature, which was absent in the
thermograms of physical mixture, signifying no interaction between
drug and the polymers.
The tensile strength was determined to evaluate mechanical
strength to the patches and found to be 287 ± 1.8. Appropriate swel-
ling behaviour of transdermal patches is an essential property for uni-
form and prolonged release of the drug and for effective skin adhesion.
The study of the hydration of polymers used in sustained release ap-
plications has been an area of interest because it is believed that it af-
fects drug release from controlled release matrix. The consequence of
water uptake could be the formation of empty spaces within the patch
that could make its structure less resistant to mechanical stresses. It
varied from 35.13 ± 1.09 to 68.13 ± 2.43 after 1 h–6 h. The swelling
ability may vary with nature and composition of patches. Hydrophilic
polymer showed considerable swelling, as it increased the surface
wettability and consequently water penetration within the matrix.
The surface pH of the patch was found to be 5.5 ± 0.08.
Considering the fact that acidic or alkaline pH may cause irritation to
the skin mucous membrane and influence the degree of hydration of
M.K. Malaiya et al.
polymers, the surface pH of the transdermal patch was determined to
optimize the drug permeation and skin adhesion. Attempts were made
to keep the surface pH close to skin pH as possible. The surface pH of
formulations was within the range of skin pH. Hence the patches will
not cause any irritation to the skin after its application. The surface pH
of formulations was determined in order to investigate the possibility of
any side effects.
Drug content was found to be 95.87 ± 2.3% of Rivastigmine tar-
trate for formulations. On this basis it was found that the drug dispersed
uniformly throughout the patch.
The drug release profile of rivastigmine tartrate from formulation is
shown in Fig. 6. Results of drug release study clearly indicate that the
drug release governed polymer interaction. No lag time was observed as
the patch was directly exposed to the dissolution medium. Slow drug
release rate was observed as the presence of ethyl cellulose in the for-
mulation. This may be due to the hydrophobic nature of the polymer,
which reduces the penetration of the dissolution medium into the
patches and retarded the drug release. Extended drug release
75.15 ± 1.43% within 24 h was observed with formulation.
The results of the permeation study indicated that the rate of drug
permeation was slow and it was found that 61 ± 1.43% of
Rivastigmine tartrate could permeate through the skin membrane in
24 h.
5. Conclusions
Alzheimer's disease (AD) is one of the most common neurodegen-
erative disorders, comprising 50–70% of all reported cases of dementia
[12] and affecting the middle to old-aged individuals [11]. The
blood–brain barrier (BBB) is a highly regulated interface that separates
the peripheral circulation and central nervous system (CNS). It is a
dynamic and functional neurovascular unit. The tight junctions be-
tween the endothelial cells serve to restrict blood-borne substances
from entering the brain. Nanotechnology based strategies have gained
tremendous importance as some of them are capable of overcoming the
limitations inherent to BBB passage. These include various types of li-
pidic, polymeric, inorganic and other types of nanoparticles (NPs) for
controlled drug delivery and release pertinent to various CNS condi-
tions [19,24]. Today about 74% of drugs are taken orally and are found
not to be as effective as desired. To improve such characters trans-
dermal drug delivery system was emerged. Drug delivery through the
skin to achieve a systemic effect of a drug is commonly known as
transdermal drug delivery and differs from traditional topical drug
delivery. Transdermal drug delivery systems (TDDS) are dosage forms
which involves drug transport to viable epidermal and or dermal tissues
of the skin for local therapeutic effect while a very major fraction of
drug is transported into the systemic blood circulation. The adhesive
character of the transdermal drug delivery system is critical to the
safety, efficacy and quality of the product. Topical administration of
therapeutic agents offers many advantages over conventional oral and
invasive methods of drug delivery. Several important advantages of
transdermal drug delivery are limitation of hepatic first pass metabo-
lism, enhancement of therapeutic efficacy and maintenance of steady
plasma level of the drug. It is expected that this approach will improve
management of drug therapy in alzheimer's patients, minimize the drug
toxicity and improve patient's compliance by delivering the drug at
controlled rate for prolonged period of time at a desired site. It is
concluded that transdermal patch bearing Rivastigmine tartarate was
able to deliver the drug at a controlled rate for an extended period of
time. The proposed system expected to be popular substituted of the
tablets and capsules. Newly developed system would likely to overcome
all the drawbacks of the presently available therapy of Rivastigmine.
Thus, developed system can be considered as an effective and con-
venience drug delivery system for treatment of Alzheimer disease.
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Journal of Drug Delivery Science and Technology 45 (2018) 408–414
Conflicts of interest
None.
Acknowledgement
Authors acknowledge Cipla Ltd Mumbai for providing Rivastigmine
and All India Council of Technical Education (AICTE) for providing
financial assistance (JRF) to one of the authors.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://dx.
doi.org/10.1016/j.jddst.2018.03.030.
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