The purpose of this research was to develop a matrix-type transdermal therapeutic system containing carvedilol with different ratios of hydrophilic and hydrophobic polymeric combinations by the solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells. The results followed Higuchi kinetics (r = 0.9953-0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies, patches coded as F3 (ethyl cellulose:polyvinylpyrrolidone, 7.5:2.5) and F6 (Eudragit RL:Eudragit RS, 8:2) were chosen for further in vivo studies. The bioavailability studies in rats indicated that the carvedilol transdermal patches provided steady-state plasma concentrations with minimal fluctuations and improved bioavailability of 71% (for F3) and 62% (for F6) in comparison with oral administration. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied using methyl prednisolone acetate-induced hypertensive rats. It was observed that both the patches significantly controlled hypertension from the first hour (P < .05). The developed transdermal patches increase the efficacy of carvedilol for the therapy of hypertension.

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The purpose of this work is intended to investigate the potential of self-nanoemulsifying (SNE) drug delivery system for enhanced oral bioavailability of etoposide by P-glycoprotein (P-gp) modulation. The components of SNE formulation were optimized by their solubilization and emulsification efficiency. The ternary phase diagrams provided nanoemulsion existence ranges and the corresponding formulations were developed and evaluated via thermodynamic and dispersibility tests. The successful formulations were characterized for various parameters including time required for self-emulsification, percentage transmittance, droplet size, surface morphology, zeta potential and in vitro release. The etoposide loaded SNE9 formulation showed 2.6- and 11-fold higher permeability coefficient in apical to basolateral direction across Caco-2 monolayers as compared to the Etosid and plain drug solution, respectively. The etoposide loaded SNE9 formulation showed a higher cytotoxicity at the highest tested concentration compared to the blank SNE9 formulation and the free etoposide. Furthermore, an in vivo pharmacokinetic study of etoposide in SNE9 formulation showed 3.2- and 7.9-fold increase in relative oral bioavailability compared with that of etoposide in Etosid and drug suspension, respectively. Thus, the developed SNE drug delivery system could be a valuable tool for the effective oral delivery of etoposide.

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