Social & Pharmacy
Social & Pharmacy
Social & Pharmacy
1
Shri Shankracharya Technical Campus Shri Shankaracharya group of Institutions, Faculty of
Pharmaceutical Sciences, Junwani, Bhilai (C.G.).
2
MJ College of Pharmacy, Junwani, Bhilai (C.G.).
ABSTRACT
Article Received on
28 Feb. 2020, Objective: The main objective of this work is to fabricate Diclofenac
Revised on 19 March 2020, Sodium transdermal patch to avoid first pass metabolism and to
Accepted on 07 April 2020,
DOI: 10.20959/wjpr20205-17296 overcome the problems associated with its biological short half-life
and fluctuations in plasma concentration upon oral administration.
Method: The patch were prepared using Solvent Casting Method,
*Corresponding Author
Gyanesh Kumar Sahu using Methyl cellulose as polymer, Dibutyl phthalate as permeation
Shri Shankracharya enhancer and Ethanol: distilled water as solvent. The physical
Technical Campus Shri evaluation of the prepared patch include organoleptic observation,
Shankaracharya Group of
moisture uptake, moisture loss, content uniformity test, stability
institutions, Faculty of
studies, swelling index, folding endurance. The drug release was
Pharmaceutical Sciences,
Junwani, Bhilai (C.G.). determined using Franz diffusion cells in phosphate buffer (pH 7.4).
Result: The result of physiochemical parameters of the transdermal
patch were found satisfactory. Formula F2 produce best result among all patchs with smooth
transparent texture and maximum folding endurance with minimum moisture loss and
moisture uptake. The patch weight, thickness were found to be uniform. The drug content in
F2 was 98%. Stability study indicates that drug remain stable for six months. Conclusion:
This work is further aimed to analyse, concentration of drug reaching in the body and to
study its effect.
KEYWORDS: Diclofenac Sodium, Transdermal patch and conventional dosage Form
1. INTRODUCTION
Since last decade, TDDS acquired a lot of interest due over the conventional dosage forms
and oral controlled release delivery, specifically for the avoidance of hepatic first pass
effect.[1] Optimization of drug release through the skin directly into the systemic circulation
and parallel minimize the retention and metabolism of the drug in the skin is the major goal
of transdermal products.[2]
Transdermal patches were developed in the 1970’s and the first transdermal system,
Transderm Scop (ciba, now Novartis) was approved by Food and Drug Administration
(FDA) in 1979 for prevention of nausea and vomiting associated with travel, particularly by
sea.[5] A Transdermal patch is a medicament adhesive patch which when applied to the skin
utilizes passive diffusion of drug at controlled rate through the skin and into the blood
stream.[6]
NSAIDs (Non-steroidal anti-inflammatory drugs) are mostly used for the preparation of
transdermal patches for the treatment of inflammation or pain. The NSAIDs patches are safer
and convenient to use than its oral dosage form. NSAIDs tablets for rheumatism leads to
various side effects like internal stomach bleeding, increased acidity, ulcers can be avoided
by using transdermal patches of NSAIDs.[7] On the other hand, the analgesic patch
of NSAIDs can be used on the site of sprain or strain. These patch when applied on the skin
in form of transdermal patch, without reaching higher plasma drug concentrations the drug
penetrate the various layer of skin in sufficient amount to exert local therapeutic effect.
Hence NSAIDs transdermal patches offers advantages of painless drug delivery, is easy to
apply, provides faster and longer relief, and have no or few gastrointestinal side effects from
the drug itself. That’s the reason now a days patients are advised to take the NSAIDs patch
over the other route because of its minimal side effects related to systemic toxicity and GIT
irritation.[8]
Mainly, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used
drugs, which are prescribed in both acute and chronic condition of rheumatoid arthritis,
osteoarthritis, dysmenorrhea treatment because of their analgesic, antipyretic and anti-
inflammatory effect. Diclofenac (2-[2-(2,6 dichlorophenyl amino) phenyl]acetic acid) is one
of the most likely and commercially successful drug in the family of NSAIDs. The main
mechanism of action of diclofenac is to inhibit the activity of cyclooxygenase (COX) by
interdicting the prostaglandin (PG) synthesis thereby controlling the synthesis of
thromboxanes and prostaglandins. The cyclooxygenase is an enzyme released during pain
and inflammation whereas, thromboxanes and prostaglandins are mediators of
[9-11]
vasoconstriction and inflammation. The drug undergoes substantial hepatic first-pass
metabolism and only about 50% of administered dose reaches systemic circulation. Its
biological half-life is also very short, it is considered as a suitable candidate to formulate it
into a sustained release matrix type transdermal patch system.[12]
The Diclofenac sodium also possesses the ideal characteristics such as poor bioavailability,
short biological half-life and smaller dose etc., to be formulated in to a transdermal patch.
Main added advantage of transdermal patches as it maintain constant and prolonged drug
level, and dose frequency is reduced, self-administration, quick onset of action and easy
termination of medication leads to provide higher level of patient compliance.[13,14]
Diclofenac was chosen as a model drug for present study as it possess near ideal
characteristic, that the drug must have in formulation to develop different transdermal matrix
films with different ratios of hydrophilic and hydrophilic –lipophilic combination containing
the drug and to perform the physicochemical and in-vitro, in-vivo evaluation along with study
of the prepared films.[15]
Diclofenac is efficiently and rapidly absorbed after conventional oral, rectal or intramuscular
administration.[16,17] After intramuscular administration peak plasma concentrations are
attained after 10 to 15 minutes. With the enteric-coated formulation peak concentration are
reached after 1.5 to 2.5 hours, and this is delayed by food to 2.5 to 12 hours. After a single
50mg dose of this formulation, mean peak plasma concentration of unchanged diclofenac is
0.7 to 1.5 mg/L.[18-21] Like other NSAIDs, diclofenac is highly (>9.5%) protein bound. The
mean total volume of distribution is 0.12 to 0.17 L/kg and that of the central compartment is
0.04 L/kg. The drug efficiently penetrates inflamed synovial fluid where high concentrations
are maintained compared with plasma concentrations. Diclofenac and its metabolites cross
the placenta in animals, and small amount may be found in the breast milk of women.[22-26]
In healthy volunteers, mean plasma clearance of diclofenac is 16 L/h, and the mean
elimination half-life of the terminal phase is 1.1 to 1.8 hours. The mean elimination half-life
after a radiolabelled dose is about 30 hours for the tracer.[27-32] The initial dosage of
conventional or enteric-coated Tablets of diclofenac is 150mg daily in 2 or 3 divided doses
with meals, and in most patients therapeutic control can be maintained on 100mg daily.[33-35]
A sustained release formulation can be administered once daily, and suppositories can be
administered once or twice daily. Intramuscular diclofenac 75mg can be given for the urgent
relief of acute pain such as renal or biliary colic. A further dose may be administered after 30
minutes if necessary, but as with oral administration the daily dosage should not exceed
150mg.[36-42]
funnel in inverted position. The solvent was allowed to evaporate and left undisturbed at
room temperature for the next 24 hour. The patch was obtained intact by slowly lifting from
the Petri dish and transdermal patches were cut into radius of 2cm2.[44-46] Ingredients to be
used are shown in Table 2.
3.5 Surface pH
Each film was allowed to swell by adding 0.5mL of distilled water on the film surface for 1hr
at room temperature. Then, pH was noted by bringing the electrode into contact to the surface
of the film and allowing it to equilibrate for 1 min.[52]
Swelling index =
Moisture loss % =
The thickness of patch was determined. It was found that F2 (0.2452mm) show less thickness
whereas F1 (0.295mm) shows more thickness.
Uniformity of weight was measured. It was found that F2 (598mg) shows more weight
whereas F4 (587mg) shows less weight.
Folding endurance of prepared transdermal patches were noted. It was found that more
folding endurance value is seen in F2 (30) and less folding endurance value in F4 (27).
4.2.5 Surface pH
Surface pH of F1 to F4 were determined. The results were tabulated in Table 8.
Swelling index after completion of 2 hour was found that F3 has more percentage of swelling
index in couple of hour and also film gets erode firstly as compare to other formulated
patches.
Moisture contents in various formulated patch were determined. It shows that F1 (2.98%) has
more moisture content and F2 (2.11%) shows less moisture content.
Moisture loss were determined and found that F3 (0.98%) shows more moisture loss and F2
(0.79%) shows less loss in moisture.
Drug content were determined. It shows that F2 with (98%) drug content and F1 (91%)
shows less drug content.
Figure 5: Graphical representation data of drug absorption by the Franz diffusion cell.
5. CONCLUSION
Transdermal application is one of the most promising method over the conventional form.
Patch of Diclofenac sodium was successfully prepared with different polymers by solvent
casting method. The present studies were helped in understanding the effect of formulation
process variables especially the concentration of different polymers on the drug release
profile. This study is further aimed to perform in-vivo studies for the concentration of
Diclofenac sodium reaching into the skin and to study its effect, which will help to avoid the
first pass metabolism and to make novel transdermal dosage form.
6. ACKNOWLEDGMENT
Authors want to acknowledge the facilities provided by the Shri Shankracharya Technical
Campus, Faculty of Pharmaceutical Sciences, Junwani, Bhilai, and Chhattisgarh. Special
thanks to Dr. A. k. Jha Sir for providing the lab to perform work.
List of Tables
Table 1. Ingredients Table of Diclofenac Sodium Patch.
Table 2.Composition of Diclofenac Sodium Transdermal Patch in Different Ratio.
Table 3. Concentration and Absorption of Diclofenac Sodium.
Table 4. Physical Appearance of Patch.
Table 5. Determination of Thickness of Patch.
Table 6. Determination of Uniformity of Weight.
Table 7. Determination of Folding Endurance.
Table 8. Determination of Surface pH.
Table 9. Determination of Swelling Index after 1 hour.
Table 10. Determination of Swelling Index after 2 hour.
Table 11. Determination of Moisture Uptake.
Table 12. Determination of Moisture Loss.
Table 13. Determination of Content Uniformity Test.
List of Figures
Figure 1. Preparation of Transdermal Patch by Solvent Casting Method.
Figure 2. Standard Graph of Diclofenac Sodium.
Figure 3. Transdermal Patch.
Figure 4. Working of Franz Diffusion Cell.
Fig 5. Graphical representation data of drug absorption by the Franz diffusion cell.
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