Coating solid dispersions on microneedles via a molten dip-coating method: development and in vitro evaluation for transdermal delivery of a water-insoluble drug

Abstract

This study demonstrates for the first time the ability to coat solid dispersions on microneedles as a means to deliver water-insoluble drugs through the skin. Polyethylene glycol (PEG) was selected as the hydrophilic matrix, and lidocaine base was selected as the model hydrophobic drug to create the solid dispersion. First, thermal characterization and viscosity measurements of the PEG-lidocaine mixture at different mass fractions were performed. The results show that lidocaine can remain stable at temperatures up to ∼130°C and that viscosity of the PEG-lidocaine molten solution increases as the mass fraction of lidocaine decreases. Differential scanning calorimetry demonstrated that at lidocaine mass fraction less than or equal to 50%, lidocaine is well dispersed in the PEG-lidocaine mixture. Uniform coatings were obtained on microneedle surfaces. In vitro dissolution studies in porcine skin showed that microneedles coated with PEG-lidocaine dispersions resulted in significantly higher delivery of lidocaine in just 3 min compared with 1 h topical application of 0.15 g EMLA®, a commercial lidocaine-prilocaine cream. In conclusion, the molten coating process we introduce here offers a practical approach to coat water-insoluble drugs on microneedles for transdermal delivery.

Keywords: coating; dissolution; solid dispersion; solubility; transdermal drug delivery.

Fig. 1. Thermogravimetric analysis (TGA) of polyethylene glycol (PEG) and lidocaine at different mass ratios

Fig. 2. Viscosity of molten polyethylene glycol (PEG) and lidocaine at different mass ratios as a function of temperature with two replicates

Fig. 3. Differential scanning calorimetry (DSC) analysis of polyethylene glycol (PEG) and lidocaine solid dispersions

Fig. 4. Microneedles coated with solid dispersions of polyethylene glycol (PEG) and lidocaine at different mass ratios

(A) Polarized-light micrographs, (B) scanning electron micrographs. Scale bar in (A) and (B) represents 200 µm.

Fig. 5. Mass of lidocaine coated on microneedle arrays (inset) after dip-coating in molten solutions containing polyethylene glycol (PEG) and lidocaine at different mass ratios

n=3 microneedle arrays per mass ratio.

Fig. 6. Delivery efficiency of microneedles coated with a solid dispersion

Solid dispersion coatings were formed on microneedles by dip-coating in a molten solution containing polyethylene glycol (PEG) and lidocaine at 50% mass ratio, and the coated microneedles were inserted in porcine skin in vitro for 3 min (A) Brightfield micrographs of coated microneedles before and after insertion providing visual evidence that most of the solid dispersion is detached from the microneedle surface, (B) mass balance quantifying lidocaine that is delivered into skin, left on skin and left on microneedle surface (n=3 microneedle arrays).

Fig. 7. Diffusion of lidocaine in porcine skin in vitro

Solid dispersion coatings were formed on microneedles by dip coating in a molten solution containing polyethylene glycol (PEG) and lidocaine at 50% mass ratio. Six arrays of microneedles were used to deliver 81 µg lidocaine into porcine skin measuring 1 cm×1 cm, in vitro, by inserting microneedles at equal spacings and leaving them inserted for 3 min. Upon removal of microneedles, the skin tissues were incubated in a humid chamber for 1, 4 or 8h (n=3 skin tissues per time point). For comparison, 0.15 g EMLA cream was topically applied on skin for 1 h. Skin samples were subsequently sectioned to quantify lidocaine that diffuses along the depth of the tissue.