Design and Evaluation of Polysaccharide-Based Transdermal Films for the Controlled Delivery of Nifedipine

Abstract

It was aimed to develop the matrix type polysaccharide-based transdermal films of nifedipine (NFD) to provide its long term plasma concentration. The mechanical tests were carried out on gel formulations which were utilised in the fabrication of transdermal films to determine the type of polymer (pectin, sodium alginate) and plasticizer (propylene glycol, glycerine) as well as their concentrations. The mechanical strength, elasticity, bioadhesiveness and the drug release characteristics of optimised films containing NFD were evaluated. Permeation of NFD from the films with/without adding an enhancer (nerolidol) was followed through excised rat skin using Franz diffusion cells. Results showed that the gels composed of either pectin or sodium alginate were appropriate for the fabrication of transdermal films of NFD, and the addition of propylene glycol improved mechanical strength, flexibility, and bioadhesiveness of the films. Permeation data showed that nerolidol was an effective permeation enhancer for the polysaccharide-based transdermal films of NFD.Key words nifedipine; transdermal film; sodium alginate; pectin; texture analysis; nerolidol Transdermal delivery possesses many advantages over conventional drug administration routes, including avoidance of intestinal and/or hepatic first pass metabolism, reduction in side effects and better patient compliance. Polymers are crucial components for the formulation of transdermal delivery systems. There are some critical parameters for the optimisation of transdermal therapeutic systems including physical or chemical stability of the formulation, compatibility with skin, adhesion to skin, the release characteristics of drug from the vehicle and its permeation through the skin. Therefore, the choice of polymers and plasticizers used in transdermal systems have strong impact on drug release, permeability, elasticity, and wearing properties of transdermal formulations. 1,2)Natural polysaccharides such as sodium alginate, chitosan, pectin, guar gum, gellan gum have been widely evaluated as a polymer in the optimisation of transdermal systems due to their non-toxic, biocompatible and potentially biodegradable properties.3,4) Sodium alginate is a mixture of polyuronic acids composed of residues of D-mannuronic acid and L-guluronic acid, which is used in design of controlled drug delivery formulations.5) It has also been used to formulate transdermal films. 6,7)Despite all the advantages of transdermal drug delivery, stratum corneum, the outermost layer of the skin, provides the greatest resistance to entrance of drugs to the systemic blood stream. In order to achieve therapeutic drug concentration following transdermal administration, penetration enhancers which reduce the barrier characteristics of stratum corneum reversibly are added into transdermal formulations. 8,9)Terpenes appear to have good skin penetration characteristics for transdermal systems due to their low cutaneous irritancies, good toxicological profiles.8) Moreover, this interaction with the stratum cor...

Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

“…We observed that eucalyptol containing gel formulation G-EU showed the highest elasticity value (0.87 ± 0.05). Bektaş et al, showed that sodium alginate as polymer at concentration of 4.5% and propylene glycol at a concentration of 7.5% as plasticizer were suitable for fabrication of transdermal films of nifedipine [5]. Our results are in accordance with this finding.…”

“…We observed that there was not a significant difference between the gel formulations G-NR, G-EU, G-TP, and G-LM in the mean of cohesiveness (p > 0.05). The cohesiveness of the sodium alginate based gels in our study ranged between 0.85 ± 0.12 and 0.91 ± 0.04 which are in accordance with literature [5].…”

“…The bioadhesion strength of polymers with ionisable carboxyl groups, such as sodium alginate was found to be stronger than that of those with neutral or non-ionisable groups [8]. The gels prepared with sodium alginate to fabricate transdermal films have been found appropriate in terms of mechanical strength, flexibility, and bioadhesiveness of the films [5].…”

“…adhesives or matrix carriers in the compositions of dermal and transdermal delivery systems [2][3][4][5]. Natural polysaccharides represent a group of polymers playing a fundamental role in controlling the mechanism and rate of drug release from a dosage form [2].…”

“…The resultant force-time plots were used for determination of the mechanical properties. Data evaluation was performed using the Texture Exponent software package of the instrument [5,30,31].…”