Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation.Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs.By many estimates up to 90% of new chemical entities (NCEs) discovered by the pharmaceutical industry today and many existing drugs are poorly soluble or lipophilic compounds [1]. The solubility issues obscuring the delivery of these new drugs also affect the delivery of many existing drugs (about 40%). Relative to compounds with high solubility, poor drug solubility often manifests itself in a host of in vivo consequences like decreased bioavailability, increased chance of food effect, more frequent incomplete release from the dosage form and higher intersubject variability. Poorly soluble compounds also present many in vitro formulation development hindrances, such as severely limited choices of delivery technologies and increasingly complex dissolution testing with limited or poor correlation to the in vivo absorption. However, important advances have been made in improving the bioavailability of poorly soluble compounds, so that promising drug candidates need no longer be neglected or have their development hindered by sub optimal formulation. In addition to more conv