Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

Abstract

The influence of formulation variables, i.e., a hydrophilic polymer (Methocel(®) E15) and a film-forming polymer (Eudragit(®) RL 100 and Eudragit(®) RS 100), on the physicochemical and functional properties of a transdermal film formulation was assessed. Several terpenes were initially evaluated for their drug permeation enhancement effects on the transdermal film formulations. D-Limonene was found to be the most efficient permeation enhancer among the tested terpenes. Transdermal film formulations containing granisetron (GRN) as a model drug, D-limonene as a permeation enhancer, and different ratios of a hydrophilic polymer (Methocel(®) E15) and a film-forming polymer (Eudragit(®) RL 100 or Eudragit(®) RS 100) were prepared. The prepared films were evaluated for their physicochemical properties such as weight variation, thickness, tensile strength, folding endurance, elongation (%), flatness, moisture content, moisture uptake, and the drug content uniformity. The films were also evaluated for the in vitro drug release and ex vivo drug permeation. The increasing ratios of Methocel(®):Eudragit(®) polymers in the formulation linearly and significantly increased the moisture content, moisture uptake, water vapor transmission rate (WVTR), and the transdermal flux of GRN from the film formulations. Increasing levels of Methocel(®) in the formulations also increased the rate and extent of the GRN release and the GRN permeation from the prepared films.

Keywords: film-forming polymers; hydrophilic polymers; permeation enhancers; transdermal films.

Fig. 1

Preparation of GRN films. a Circular glass mold in a Petri dish filled with mercury, b Mold covered with an inverted funnel to qualitatively control solvent evaporation, and c Dried GRN film

Fig. 2

Effect of penetration enhancers on the permeation of GRN. All values are mean ± SD (n = 3). *P < 0.01, compared to control

Fig. 3

FTIR analysis of the drug and the polymers. a Granisetron, b granisetron:Methocel^® E15:Eudragit^® RL 100 (1:1:1), and c granisetron:Methocel^® E15:Eudragit^® RS 100 (1:1:1)

Fig. 4

The effect of Methocel^® E15 levels on the moisture content (%) of the prepared films. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100

Fig. 5

The effect of Methocel^® E15 levels on the moisture uptake (%) of the prepared films. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100

Fig. 6

The effect of Methocel^® E15 levels on the water vapor transmission rate of the films. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100

Fig. 7

The in vitro release of GRN from transdermal films. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100 (n = 3)

Fig. 8

The ex vivo permeation of GRN from transdermal films. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100 (n = 3)

Fig. 9

Transdermal flux of GRN from the film formulations. a Formulations containing Eudragit^® RL 100. b Formulations containing Eudragit^® RS 100

Fig. 10

Permeability coefficient and enhancement ratio of GRN from transdermal films. Values are mean ± SD (n = 3)