Transdermal delivery of an antihypertensive drug

Abstract

Purpose: the first objective of this thesis was to deliver lisinopril (LSP) through skin to enhance its bioavailability allowing use of lower drug doses. To achieve our goal, transdermal films formed of the composite matrix composed of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone K-30 (PVP) were prepared and evaluated. Two mechanisms of skin permeation were attempted throughout this work: the use of common permeation enhancers (PE) e.g. glycerol (GLY) and propylene glycol (PG), and the use of flexible nanoethosomes. Finally, an in vivo study was used to evaluate the bioavailability of LSP following application of the transdermal films to rabbits and the results were compared to oral administration. Tolerability of the developed matrix based transdermal films were also evaluated following application on rats by histological examination.

Methods: Composite matrix films comprising PVA modified with PVP were first developed. The selected PE were incorporated in the composite matrix and their effects on the properties of the matrix were thoroughly investigated.

In chapter Ӏ: GLY and PG were used for their permeation enhancement in addition to their plasticizing effects for the polymers PVA and PVP. The compatibility of LSP with the film formulation