DESIGN OF DICLOFENAC SODIUM TRANSDERMAL FILMS: PREPARATION, PHYSICAL CHARACTERIZATION, EX VIVO AND IN VIVO STUDIES
DESIGN OF DICLOFENAC SODIUM TRANSDERMAL FILMS: PREPARATION, PHYSICAL CHARACTERIZATION, EX VIVO AND IN VIVO STUDIES
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Date
2014-05
Authors
OGWU, Nkechi Ngozi
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Abstract
Diclofenac sodium is a non steroidal anti-inflammatory drug, which undergoes potential problems such as substantial hepatic first pass effect and gastrointestinal irritation when given through the oral route, and this necessitates an alternative choice of route for the administration of such drugs. The aim of this study was to formulate diclofenac sodium into a transdermal film using blends of Eudragit RS 100 (a hydrophobic polymer) and Hydroxypropylmethylcellulose HPMC (a hydrophilic polymer) as matrices, and to evaluate the formulation. The films were prepared by the solvent casting technique using diclofenac sodium as the drug of choice, plasticizer (PEG 8000), permeation enhancer (Tween 80), and varying the combinations of film forming polymers (Eudragit RS 100 and HPMC). The formulated films were subsequently evaluated for any possible interaction which may occur between the drug and the excipients using the Fourier Transform Infrared Spectroscopy (FT-IR) and the Differential Scanning Calorimetry (DSC) Technique. The physicochemical characteristics of the formulated films were evaluated with reference to their physical appearance, weight uniformity, thickness uniformity, folding endurance, moisture uptake, moisture loss, flatness and drug content. Ex vivo studies were also carried out using a modified Franz diffusion cell, and the films that showed the best pattern in terms of permeation rate were further studied for their in vivo anti inflammatory activities. Skin irritation studies were carried out, as well as stability studies at room temperature under a relative humidity of 75%. The FT-IR and DSC spectroscopy revealed that the drug was compatible with the excipients used in the formulation, while the physicochemical properties showed that films with a higher proportion of HPMC gave good mechanical and flexibility properties. The ex vivo permeation studies revealed that formulation F1 and F7 with a greater proportion of HPMC, gave a faster rate of permeation, with a cumulative
amount of drug permeation of 57.10 % and 45.61 % respectively, while formulation F5 with a high proportion of Eudragit RS 100 gave the least rate of permeation of 18.79 %. The in vivo anti inflammatory studies indicated that the edema volume for the test group remained well below that of the control group, and percentage inhibition was found to be 79 % and 88 % respectively for F1 and F7. The result of the skin irritation test revealed no erythema and no edema with the formulated films F1 and F7. The data obtained from the stability studies showed no change in the physical appearance and drug content of the formulated films, indicating that they are relatively stable. The result obtained indicates the feasibility for a transdermal delivery of diclofenac sodium using Eudragit RS 100 and HPMC polymer blends as matrices
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES,
AHMADU BELLO UNIVERSITY, ZARIA
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR AWARD OF THE DEGREE OF MASTER OF SCIENCE IN PHARMACEUTICS
DEPARTMENT OF PHARMACEUTICS AND PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACEUTICAL SCIENCES
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA
JUNE, 2014
Keywords
DICLOFENAC,, SODIUM,, TRANSDERMAL,, PREPARATION,, PHYSICAL,, CHARACTERIZATION,,, EX VIVO,, IN VIVO,