Development of a nanogel formulation for transdermal delivery of tenoxicam: a pharmacokinetic–pharmacodynamic modeling approach for quantitative prediction of skin absorption. (3rd April 2017)

• Record Type: Journal Article
• Authors: Elkomy, Mohammed H.; El Menshawe, Shahira F.; Eid, Hussein M.; Ali, Ahmed M. A.
• Is Part Of: Drug development and industrial pharmacy. Volume 43:Number 4(2017)
• Page Start: 531
• Page End: 544
• Publication Date: 2017-04-03
• Subjects: tenoxicam -- solid lipid nanoparticles -- transdermal -- pharmacokinetics -- pharmacodynamics -- skin absorption; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2016.1268153
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: This study investigates potentials of solid lipid nanoparticles (SLN)-based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetic–pharmacodynamic (PK–PD) modeling approach for predicting concentration–time profile in skin. A 2 3 factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan-induced rat paw edema test. A published Hill model for in vitro inhibition of COX-2 enzyme was fitted to edema inhibition data. Concentration in skin was represented as a linear spline function and coefficients were estimated using non-linear regression. Uncertainty in predicted concentrations was assessed using Monte Carlo simulations. The optimized SLN was spherical vesicles (58.1 ± 3.1 nm) with adequate entrapment efficiency (69.6 ± 2.6%). The SLN-gel formulation was well-tolerated. It increased TNX activity and skin level by 40 ± 13.5, and 227 ± 116%, respectively. Average C max and AUC0–24 predicted by the model were 2- and 3.6-folds higher than the corresponding values computed using in vitro permeability data. SLN-gel is a safe and efficient carrier for TNX across skin in the treatment of inflammatory disorders. PK–PD modeling is a promising approach for indirect quantitation of skin deposition from PD activity data.