Factors affecting topical delivery of Propylthiouracil from Niosomal systems

Abstract

|aNiosomes, a relatively new class of vesicular dosage forms, are thought to be a good alternative to phospholipids-based liposomes since they are more stable and less costly than liposomes. In this study, Propylthiouracil (PTU), a lyophobic drug with an antiproliferative activity, was formulated into niosomes for topical treatment of psoriasis. The study focused on the effects of formulation factors on topical delivery of PTU from niosomal systems prepared from various classes of non-ionie surfactants. PTU niosomes were prepared by the sonication method that was devoid of organic solvent. Characterization of PTU niosomes regarding entrapment efficiency, size and size distribution, phase transition, bilayer elasticity, stability, and drug release was performed. PTU permeation from some selected niosomal formulations across newborn pig skin was studied using modified Franz diffusion cells. The effects of formulation factors, which included the thermodynamic state of vesicular bilayer, surfactant type, and existence of vesicular structure, on PTU delivery across the skin were investigated. The dominating mechanism of PTU skin permeation from niosomes was also elucidated. The results revealed that niosomes readily formed from various compositions of non-ionic surfactant and either cholesterol or octaoxyethyleneglycol-8- laurate ester, with or without a stabilizer. Entrapment efficiency and vesicle size of PTU niosomes depended on the composition of both the vesicles and the aqueous phase. All niosomal formulations were stable within two months of storage at ambient temperature. The release of PTU from all niosomes studied was retarded and followed the first- order kinetics. The release rate constants depended on drug entrapment as well as thermodynamic state of the bilayer. All formulation factors studied could affect PTU permeation, depending on the niosomal compositions. The mechanisms involving entrapment efficiency and diffusion of free drug that was released from niosomal vesicles were not the dominating mechanisms of PTU delivery from niosomes. On the other hand, penetration-enhancing properties of the vesicular components and the mechanism involving vesicle-skin transfer were likely to be the dominating mechanisms of PTU delivery from niosomal systems studied. The results of this study indicate that topical delivery of PTU from niosomes could be modulated by modification of niosomal formulations.