Nebulized oil-in-water nanoemulsion mists for pulmonary delivery: development, physico-chemical characterization and in vitro evaluation.

CONTEXT

This study presents novel nanostructured oil-in-water (o/w) mists based on self-nanoemulsifying (SNE) mixtures capable of delivering poorly water-soluble drugs into the lungs.

OBJECTIVE

Formulation development of an o/w nanoemulsion (NE) capable of being nebulized for pulmonary delivery of poorly water-soluble drugs.

MATERIALS AND METHODS

SNE mixtures were prepared and evaluated using Tween 80 and Cremophor RH 40 as surfactants; Transcutol P, Capryol 90 and PEG 400 as cosurfactants; and Labrafac Lipophile Wl 1349 (a medium-chain triglyceride) as an oil. Liquid NEs were analyzed by light scattering, zeta potential, transmission electron microscopy (TEM) and in vitro drug release studies. The aqueous NE was nebulized and assessed by light scattering and TEM. The formulation was aseptically filtered and the sterility validated. In vitro cytotoxicity of the formulations was tested in NIH 3T3 cells. The capability of the formulation to deliver a poorly water-soluble drug was determined using ibuprofen.

RESULTS

Ibuprofen was found to be stable in the NEs. The formulations were neutrally charged with a droplet size of about 20 nm. TEM images displayed 100 nm oil droplets. The aseptic filtration method produced sterile NE. The nebulized mist revealed properties ideal for pulmonary delivery. The biocompatible aerosol has a nanostructure consisting of several oil nanodroplets enclosed within each water drop. Solubility and in vitro drug release studies showed successful incorporation and release of ibuprofen.

CONCLUSION

The developed formulation could be used as an inhalation for delivering material possessing poor water solubility into the lungs.