PREPARATION AND IN-VITRO EVALUATION OF DICLOFENAC SODIUM TRANSDERMAL PATCHES

 

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ABOUT AUHTOR
SUSMITA DAS*
Department of Pharmaceutical Technology, 
Jadavpur University,
West Bengal, India

*sdas53662@gmail.com

ABSTRACT:
Objectives: The aim of the present study was to develop transdermal matrix patches with a fixed ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC), containing the drug diclofenac sodium and to perform the physicochemical, in vitro relese pattern evaluation of the prepared patches. The prospective objective was the demonstration that the system provides the delivery of drug at a controlled rate across intact skin to achieve a therapeutically effective drug level for a longer period of time from transdermal patches.
Methods: In this study, matrix-type transdermal patches containing diclofenac sodium were prepared using different ratio of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), and in-vitro release kinetics and permeation studies were performed across cadaver skin using a modified diffusion cell.
Results and conclusion: Variations in drug release profiles among the formulations studied were observed. From the formulated patches FA 1, containing PVP/EC in ratio of 1:3 shows sustained release action with 38% release after 24 h and 10 µg of drug permeation accross 1 cm2 of patch area. Hence, it can be reasonably concluded that diclofenac sodium can be formulated into the transdermal matrix type patches to sustain its release characteristics for manufacturing transdermal patches of diclofenac sodium

REFERENCE ID: PHARMATUTOR-ART-2482

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 5, Issue 4

Received On: 20/12/2016; Accepted On: 28/12/2016; Published On: 01/04/2017

How to cite this article: Das S;Preparation and In-Vitro evaluation of Diclofenac Sodium Transdermal Patches; PharmaTutor; 2017; 5(4); 46-54

INTRODUCTION
Administration of drugs  in the conventional dosage forms usually results in large range fluctuations in plasma drug concentrations leading to undesirable toxicity or poor effectiveness along with limitations such as repetitive dosing and unpredictable absorption, led to the concept of the controlled drug delivery system or therapeutic system.[1] Skin is a well researched and easily approached target which declares its versatility in terms of advantages such as maintenance of constant and prolonged drug level, reduced frequency of dosing, minimization of inter- and intra-patient variability, self administration, and easy termination of medication, leading to patient compliance.[2] Anatomically skin is a multilayered organ comprising three layers from outsides acting as a primary physical immunological barrier.[2,3] The blood flow in different regions are highly variable pertaining to the relative permeability and cellular density which makes the difference in pattern of drug absorption along with several other factors like hydration of skin, contact time and temperature of the area. There are three major routes of penetration across the membrane namely transcorneal, intra follicular and intra appendeageal penetration. On an average, the human skin surface contains 40-70 hair follicles and 200-250 sweat ducts per cm2 and these skin appendages play an important role in the permeation of drug at an early and steady state. [4]

Diclofenac is a widely prescribed nonsteroidal anti-inflammatory drug, widely used in musculoskeletal disorders, arthritis, toothache, dysmenorrhea, etc., for symptomatic relief of pain and inflammation.[5] Sodium salt of diclofenac which is slightly acidic is reportedly used for topical applications and it has a molecular weight of 296.149 which is administered in dose of 25-50 mg oral daily. The limitation pertaining to the oral delivery of the drug undergoes substantial hepatic first-pass metabolism by CYP 450 2C9 and UDP-glucuronosyltransferase and thus only about half of the administered dose reaches systemic circulation.[6]

 

Transdermal therapeutic systems are defined as medicated dosage forms in form of patch which, when applied to the intact skin, deliver specific dose of drug(s), through the skin, at a controlled rate to the systemic circulation. The drug has a log P value of 4.5 conforming high lipid solubility along with 98% of protein binding. The elimination half-life is 1.2-2 h with clearance of  65% drug unchanged and 35% metabolized in urine. The drug has volume of distribution of 1.4 L. These factors suggests it to be a suitable candidate for incorporation into matrix patches to enhance the delivery.[7]

The first transdermal drug delivery (TDD) system, Transdermal Scop, developed in 1979, used the drug scopolamine for the treatment of motion sickness and over the last two decades more than 35 transdermal patch products have been approved in US. 2004 patch sales in the US were approximately $3.4 billion.[3] Current drugs utilized in TDD systems include nicotine, nitroglycerin and various hormones such as estradiol and testosterone etc and a market analyis is shown in figure 1.

Figure 1: Chart according to the marketability of different patches

Some FDA Approved and widely used marketed Dicofenac patches are FLECTOR® Patch (diclofenac epolamine topical patch)[12] and NuPatch® drug delivery system (India’s first indigenously manufactured patch formulated by Zydus Cadila)[5]

The aim of the present study was to develop different transdermal matrix patches with fixed ratio of polyvinylpyrrolidone (PVP) and ethylcellulose (EC), containing the drug diclofenac sodium and to perform the physicochemical, and in-vitro evaluation of the prepared patches. The purpose was to provide the delivery of drug at a controlled rate across intact skin to achieve a therapeutically effective drug level for a longer period of time from transdermal patches. In this approach, the drug reservoir is formed by homogeneously dispersing of drug solids in a polymeric matrix composed of a suitable blend of PVP K-30 and EC and then molded into medicated disc with a defined surface area and controlled thickness followed by evaluation in-vitro and in-vivo.

MATERIALS AND METHODS:
Diclofenac sodium was obtained as gift sample from Micro Labs Ltd., Hosur, India. Polyvinylpyrrolidone (PVP) (Loba Chemie Pvt Ltd, Mumbai, India), polyvinyl alcohol (PVA) (molecular weight 125,000 Dalton, viscosity of 4% aqueous solution at 20 °C is 23  - 38  cp), tween 80 and ethyl cellulose (EC) (Ethoxy content 47.5–49%, viscosity 14 cps in 5% w/w solution in 80:20 toluene/ethanol at 25°C) (SD Fine-Chem. Ltd., Mumbai, India), dibutyl phthalate (DBP) (Qualigens Fine Chemicals, Mumbai, India) were procured. All the other chemicals used were of analytical grade.

Preparation of backing membrane
The bottom of the mold was wrapped with aluminium foil. Adequately weighted PVA was solubilised into preheated water by slow addition into the water by constant stirring till it forms a homogeneous  solution. On the  aluminium foil  backing membrane was cast by pouring 2% w/v PVA Solution and 4%  w/v PVA Solution into glass molds (2.55 cm inner diameter and 2 cm height) followed by drying at 80°C for  24 h. Initially from the above two combinations 4% w/v was screened to achieve appropriate consistency and tensile strength and used for future backing membrane preparation.[8,11,12]

Casting of matrix containing the drug to form transdermal patches:
Matrix-type transdermal patches containing diclofenac sodium were prepared using the 1:2 ratio of PVP and EC by solvent evaporation technique in cylindrical both sides open glass molds (Figure 6). The two polymers were weighed in requisite ratio and they were then dissolved in chloroform. Di-n-Butyphthalate 30% w/w of polymer composition was used as a plasticizer. The drug was added, calculating an amount of  20% w/w of polymer per mold, in the homogeneous dispersion, by sonicating it with an ultra sonicator followed by slow stirring  with a mechanical stirrer. 2 mL of the uniform dispersion was cast on the PVA backing membrane cast earlier and dried at 60°C for 24 h. They were kept in desiccators until used.[8,12]

Formulation Code

Rario of PVP/EC

Total weight of PVP and EC (mg)

Chloroform

(mL)

di-n-Butylphthalate

Drug

FA 1

1:3

600

10

30% w/w of polymers

20% w/w of polymers

FA 2

1:2

600

10

30% w/w of polymers

20% w/w of polymers

FA 3

1:1

600

10

30% w/w of polymers

20% w/w of polymers

FA 4

2:1

600

10

30% w/w of polymers

20% w/w of polymers

FA 5

3:1

600

10

30% w/w of polymers

20% w/w of polymers

Table 1: Composition of the prepared batches of transdermal patches

In-vitro evaluation of prepared transdermal patches:
Physicochemical parameters test:
Weight variation test:
Randomly selected twenty patches from each type were directly weighed on a digital balance (Sartorius, GD-103, Goettingen, Germany) and average mass was calculated. Deviations of mass of individual patch from the mean value were determined.[9,10]

Diameter and area of patch:
The diameter (D) of  the whole patch (adhesive matrix with the drug(s) plus the backing membrane) was measured at five different randomly selected points of 10 patches using digital calipers (Digmatic Massschieber, CD-6, CSX, Mitutoyo Corp., Japan) in mm scale and average diameter and area (πD2/4) were determined.[11,12].

Thickness of the patches:
The thickness of the backing membrane and the whole patches were measured using digital calipers (Digmatic Masschieber, model CD-6 CS, Mitutoyo, Tokyo). The average thickness of the backing membrane and the whole patch were determined.[11]

Moisture content:
The prepared films were marked, weighed individually and kept in a desiccator containing anhydrous silica at room temperature for 24 h. The mass was taken time to time till it became constant. [11]  Percent moisture content was determined as follows:

% Moisture content = X- Y /X × 100  ; where X = initial mass, Y= final mass

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