A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation

Abstract

The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of dexamethasone using blends of two different polymeric combinations, povidone (PVP) and ethylcellulose (EC) and Eudragit with PVP. Physical studies including moisture content, moisture uptake, flatness to study the stability of the formulations and in vitro dissolution of the experimental formulations were performed to determine the amount of dexamethasone present in the patches were performed and scanning electron microscopy (SEM) photographs of the prepared TDDS were taken to see the drug distribution pattern. Drug–excipient interaction studies were carried out using Fourier transform infrared (FTIR) spectroscopic technique. In vitro skin permeation study was conducted in a modified Franz's diffusion cell. All the formulations were found to be suitable for formulating in terms of physicochemical characteristics and there was no significant interaction noticed between the drug and polymers used. In vitro dissolution studies showed that the drug distribution in the matrix was homogeneous and the SEM photographs further demonstrated this. The formulations of PVP:EC provided slower and more sustained release of drug than the PVP:Eudragit formulations during skin permeation studies and the formulation PVP:EC (1:5) was found to provide the slowest release of drug. Based on the above observations, it can be reasonably concluded that PVP–EC polymers are better suited than PVP–Eudragit polymers for the development of TDDS of dexamethasone.

Introduction

Transdermal drug delivery is the delivery of drugs across epidermis to achieve systemic effects. The success of transdermal patches lies in their commercialization. Transdermal patches control the delivery of drugs at controlled rates by employing an appropriate combination of hydrophilic and lipophilic polymers [1], [2], [3], [4].

Dexamethasone, a synthetic glucocorticoid [5] suppresses inflammation [6] and normal immune response [7]. It is widely used as a therapeutic agent in alcohol withdrawal syndrome [8], cerebral oedema [9], congenital adrenal hyperplasia [5], nausea and vomiting specially associated with high dose of anticancer agents [10], high altitude disorder, cerebral malaria, opportunistic mycobacterial infections, respiratory disorders, skin disorders [5], rheumatism [11], meningitis, early mild carpal tunnel syndrome and as a diagnostic agent in Cushing's syndrome [12]. Commercial topical preparations of dexamethasone include dexamethasone aerosol, dexamethasone gel [13] among others. Although a good number of topical gel formulations of dexamethasone are available, they are not suitable for prolonged, controlled and systemic delivery of the drug through intact skin. Moreover, they are not a suitable drug delivery option to transdermal patches. Topical dexamethasone administered as an osmotic pump to brain tumor beds resulted in an increase in survival similar to systemic dexamethasone. To avoid complications of systemic steroid treatment, dexamethasone given topically is a more suitable alternative in such conditions [14]. Moreover, dexamethasone possesses most of the ideal physicochemical and biological properties, e.g. biological half-life ranging between 2 and 5 h, plasma protein binding nearly about 67%, a small dose ranging from 0.5 to 9 mg daily, hepatic first pass effect of the drug and gastric irritation upon oral administration [15], to be formulated into a transdermal patch type delivery system. A number of researchers have also reported some methodologies for increasing the transdermal absorption of dexamethasone from solution/gel formulation by employing iontophoresis [16] and phonophoresis [17], [18]. But so far, no work related to the development of pre-filled transdermal patches of dexamethasone has been reported in the literature.

The system designs for transdermal patches include matrix, microreservoir, reservoir, adhesive and membrane–matrix hybrid. Matrix type transdermal patches remain among the most popular, as they are easy to manufacture.

The present study was designed to develop a suitable matrix patch type transdermal drug delivery system (TDDS) for dexamethasone employing various ratios of polyvinylpyrrolidone (PVP) and EC as well as PVP and Eudragit^®. The aim was to compare the polymeric combinations in terms of in vitro skin permeation of the drug and to find out the best possible ratio of hydrophilic and lipophilic polymeric combination, which may be chosen for further studies.