Abstract
Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.
KEY WORDS: Transdermal drug delivery system, plasticizer, diclofenac sodium
Diclofenac is non steroidal anti-inflammatory agent, widely used in musculoskeletal disorders, arthritis, toothache, etc., for symptomatic relief of pain and inflammation. It is reportedly used for topical applications. The drug undergoes substantial hepatic first-pass metabolism and only about 50% of administered dose reaches systemic circulation. This originates the need of an alternative choice of route of administration for such drugs. 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.[1]
Transdermal patches offer added advantages such as maintenance of constant and prolonged drug level, reduced frequency of dosing, self administration and easy termination of medication leading to patient compliance.[2] Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch.
Subjects and Methods
Method
The casting solutions were prepared by dissolving weighed quantities [Table 1] of polymers, plasticizer and drug in to solvent compositions. The casting solution (10 ml) was poured into glass petridishes and dried at room temperature for 24 h for solvent evaporation. The patches were removed by peeling and cut into square dimension of 3 cm×3 cm (9 cm2). These patches were kept in dessicator for 2 days for further drying and wrapped in aluminum foil, packed in self-sealing covers.[3]
Table 1.
Composition of formulations
Evaluation
All the transdermal patches were visually inspected for colour, flexibility, homogenecity and smoothness.
The thickness of the patches was measured at five different places on a single patch of each formulation using a screw gauge and the mean values were calculated.
Patch having a diameter of 1 cm2 was weighed on a digital balance and the mean values were calculated.
A strip of 2 cm×2 cm (4 cm2) was subjected to folding endurance by folding the patch at the same place repeatedly several times until a visible crack was observed and the values were reported which is indication of brittleness of the film.
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 to measure elasticity.[4]
Each patch from different formulations (patch size of 1 cm2) was transferred into a graduated flask and phosphate buffer pH 6.8 was added up to 100 ml mark for extracting the drug from the patch. After extraction of the drug, the solution was filtered and the absorbance was measured at 276 nm, against the placebo patch solution as blank and the drug content was calculated.
In vitro drug release profiles were carried out by using modified Keshery-Chein diffusion cell with cellophane membrane using pieces of 7 cm2 area. One patch of 1 cm2 was placed in the donor compartment of the diffusion cell. The receptor fluid (5 ml) was withdrawn after 24 hr and was analyzed for drug content at 276 nm using UV-visible spectrophotometer.
Results
In view of low permeability of DS, monolithic device of drug has been attempted. Transdermal patches were studied for clarity, elasticity, folding endurance, and ease of removal of films from the molds and also for thickness uniformity, drug content and in vitro drug release profile [Table 2]. Study shows that HPMC and EC are good polymers rather than PVP and PVA (TP1 to TP6). With HPMC and EC, glycerin shows good folding endurance and elasticity as compared to PEG-4000. These both polymers and glycerin shows good solubility and dispersivity in acetone:water solvent composition by giving transparent patch (TP2 and TP5).
Table 2.
Physicochemical properties of the prepared transdermal patches
Conclusion
Present study can conclude that HPMC shows a better transdermal patch of diclofenac sodium in combination with glycerin as a plasticizer in solvent acetone:water (TP2). As the compositions for fabrication of patch is varied, physicochemical properties of the patch is also varied. Sometimes breakable patches are also observed (TP7 and TP9).
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
References
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