Ke Peng

Abstract

Gelled non-toxic bicontinuous microemulsions have great potentials in transdermal drug delivery. The bicontinuous microemulsion provides optimum drug solubilisation and promotes skin permeation, while the gel network provides mechanical stability and an easy application. For the first time, we have formulated such a gelled non-toxic bicontinuous microemulsion consisting of H2O, isopropyl myristate (IPM), the non-ionic sugar-based surfactant Plantacare 1200 UP (C12G1.4), 1,2-octanediol, and the low molecular weight gelator 1,3:2,4-dibenzylidene-D-sorbitol (DBS). In this study, we solubilised both hydrophobic and hydrophilic model drugs in the non-toxic bicontinuous microemulsion, namely lidocaine and diclofenac sodium salt. We found that the microemulsion allows for the solubilisation of designated amounts of both model drugs in the same formulation. Interestingly, the combination of both drugs led to the unexpected stabilisation of a scattering one-phase formulation without adding the surfactant Plantacare 1200 UP. Furthermore, the drug-loaded microemulsions were gelled by DBS without altering the phase behaviour. Finally, we found the rheological behaviour of the drug-free and drug-loaded microemulsions to be quite similar. These results suggest that the drug-containing gelled bicontinuous microemulsion is an orthogonal self-assembled system with a high potential for the use in transdermal drug delivery.

Abstract

Gelled non-toxic microemulsions have great potential in transdermal drug delivery: the microemulsion provides an optimum solubilizing capacity for drugs and promotes drug permeation through the skin barrier, while the gel network provides mechanical stability. We have formulated such a gelled non-toxic microemulsion consisting of H2O – isopropyl myristate (IPM) – Plantacare 1200 UP (technical-grade alkyl polyglucoside with an average composition of C12G1.4) – 1,2-octanediol in the presence of the low molecular weight gelator (LMWG) 1,3:2,4-dibenzylidene-d-sorbitol (DBS) at an oil-to-water ratio of ϕ = 0.50. The study at hand aimed to develop gelled non-toxic microemulsions that can contain both oil- and water-soluble drugs and are either water- or oil-based, depending on the application. To accomplish this, we varied the oil-to-water ratio from being water-rich to oil-rich, i.e. 0.2 ≤ ϕ ≤ 0.8. Phase studies were carried out along the middle phase trajectory, and a suitable LMWG was identified for all ϕ-ratios. Electrical conductivity measurements showed that the structure can be tuned from water- to oil-continuous by adjusting the amount of 1,2-octanediol and ϕ-ratios. The existence of the gel network was visualized by freeze-fracture electron microscopy (FFEM) at three different ϕ-ratios. We found that all systems from ϕ = 0.35 to ϕ = 0.80 form strong gels with nearly the same rheological behavior, while the system with ϕ = 0.20 is a much weaker gel. We attribute this behavior on the one hand to the microemulsion microstructure and on the other hand to the solvent-dependent gelation properties of DBS, which can be described by the Hansen solubility parameters (HSPs).

Abstract

Gelled non-toxic bicontinuous microemulsions have a great potential for transdermal drug delivery as the microemulsion facilitates the solubilization of both hydrophilic and hydrophobic drugs, while the gel network provides mechanical stability and thus an easy application on the skin. In our previous study, we formulated a gelled non-toxic bicontinuous microemulsion: we gelled the system H2O–isopropyl myristate (IPM)–Plantacare 1200 UP (C12G1.4)–1,2-octanediol with the low molecular weight organogelator 1,3:2,4-dibenzylidene-d-sorbitol (DBS). However, a large amount of Plantacare 1200 UP (12 wt %) is needed to form a bicontinuous microemulsion. To solve this problem, we studied a new class of surfactants, namely, alkanoyl methylglucamides (MEGA), which have been rarely used for the formulation of microemulsions. The phase behavior of microemulsions stabilized by MEGA-8/10, MEGA-12/14-PC, and MEGA-12/14-HC was compared with that of systems stabilized by alkyl polyglucosides. We found that even with 2 wt % MEGA-12/14-HC, a bicontinuous microemulsion can be formed, which is 1/6 of the amount of Plantacare 1200 UP. The bicontinuous microstructure of the non-toxic microemulsion H2O–IPM–MEGA-12/14-HC–1,2-octanediol was confirmed by small-angle neutron scattering. Furthermore, the phase boundaries remained unchanged when gelled by DBS. The rheological properties of the gel were studied by oscillatory shear rheometry. Finally, freeze-fracture electron microscopy images show the coexistence of gel fibers and bicontinuous oil and water domains. These results suggest that the new gelled non-toxic bicontinuous microemulsion is an orthogonal self-assembled system.

Abstract

Bicontinuous microemulsions gelled with a low molecular weight gelator have been shown to be an orthogonally self-assembled system. With the mechanical stability provided by the gel network, gelled non-toxic bicontinuous microemulsions have the potential to be an efficient transdermal drug delivery carrier. However, up to now no suitable system has been formulated for transdermal drug delivery. To fill this gap, we formulated and characterized a gelled non-toxic bicontinuous microemulsion suitable for the mentioned application. Starting from a previously studied scouting system, namely, H2O–n-octane–n-octyl β-d-glucopyranoside (β–C8G1)–1-octanol, the co-surfactant and the oil were replaced by non-toxic components. Subsequently, the expensive pure surfactant was replaced by cheap technical-grade surfactants (Plantacare® series) to make the system economical. Having formulated the non-toxic microemulsion H2O–IPM–Plantacare 1200 UP–1,2-octanediol, three low molecular weight gelators were studied with regard to the gelation of both the scouting system and the non-toxic system. The chosen gelators were 12-hydroxyoctadecanoic acid (12-HOA), 1,3:2,4-dibenzylidene-d-sorbitol (DBS), and N,N′-dibenzoyl-l-cystine (DBC). We found that only DBS gels the non-toxic microemulsion. The gelled non-toxic bicontinuous microemulsion H2O–IPM–Plantacare 1200 UP–1,2-octanediol was characterized with oscillatory shear rheometry and small-angle neutron scattering (SANS) at a DBS concentration of 0.3 wt% to verify that the system is indeed a gel and that the microstructure of the microemulsion is not altered by the gel network.