Development and evaluation of microemulsions for transdermal delivery of insulin

Abstract

Insulin-loaded microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant. The pseudoternary phase diagrams were constructed to determine the composition of microemulsions. The insulin permeation flux of microemulsions containing oleic acid as oil phase through excised mouse skin and goat skin was comparatively greater than that of microemulsions containing isopropyl myristate as oil phase. The insulin-loaded microemulsion containing 10% oleic acid, 38% aqueous phase, and 50% surfactant phase with 2% dimethyl sulfoxide (DMSO) as permeation enhancer showed maximum permeation flux (4.93 ± 0.12 μg/cm(2)/hour) through goat skin. The in vitro insulin permeation from these microemulsions was found to follow the Korsmeyer-Peppas model (R(2) = 0.923 to 0.973) over a period of 24 hours with non-Fickian, "anomalous" mechanism. Together these preliminary data indicate the promise of microemulsions for transdermal delivery of insulin.

Figure 1

Pseudoternary phase diagrams of (a) oil (isopropyl myristate), surfactant (Tween 80/isopropyl alcohol, in 3 : 1 ratio), and aqueous phases and of (b) oil (oleic acid), surfactant (Tween 80/isopropyl alcohol, in 3 : 1 ratio) and aqueous phases. The shaded area signifies the microemulsion zone.

Figure 2

In vitro insulin permeation profile through mouse skin per unit area from insulin-loaded microemulsions (mean ± standard error, n = 3).

Figure 3

In vitro insulin permeation profile through goat skin per unit area from selected insulin-loaded microemulsions (F3 and F6) without and with 2% DMSO as permeation enhancer (F7 and F8). (mean ± standard error, n = 3).

Figure 4

The droplet size distribution curves of the selected insulin-loaded microemulsions: (a) F3 and (b) F6.