|M.Sc Student||Gefen-Azran Adi|
|Subject||Matrices for Controlled Release of Amiodarone|
|Department||Department of Polymer Engineering||Supervisor||Professor Havazelet Bianco-Peled|
|Full Thesis text|
The therapeutic application of hydrophobic agents is associated with some difficulties. Low solubility often results in low bioavailability and absorption rates with a possibility of high local concentrations which might lead to toxicity. Amiodarone is an example for such a poorly soluble drug. It is an anti-arrhythmic drug, widely used to treat heart diseases, but also provokes severe adverse effects due to its accumulation in tissues other than the heart. In recent years, polymeric micelles have been the object of growing scientific attention. They have emerged as a potential carrier for poorly water soluble drugs because they can solubilize those drugs in their inner core. In addition, polymeric micelles offer attractive characteristics such as a generally small size (under 100 nm) and a propensity to evade scavenging by the mononuclear phagocyte system.
The main aim of the current research was to develop and characterize a sustained release system for the delivery of amiodarone based on a thermo-sensitive block copolymer Pluronic? F127 and a nonionic surfactant, Tween 80. The phase diagram of a mixed micellar system Pluronic? F127/Tween 80/water was characterized in terms of its ability to gel at 37°C and its ability to solubilize amiodarone. Feasible formulations were identified and further investigated to determine amiodarone release from the gel. These experiments revealed that the total release time was several days. Texture analysis of the gel detected that the mechanical integrity of the gel has substantially decreased during the first hours of drug release. The gel was completely dissolved after two to three days in physiological conditions. In addition, a linear relation between the release of amiodarone and the degradation of the matrix has been demonstrated, linking between the mechanical degradation of the gel to the drug release. The structure of the gel was characterized using small angle X-ray scattering (SAXS) and found to be body centered cubic (BCC) with a lattice parameter of 18.5 nm. Amiodarone release mechanism from the gel was characterized using in-vitro release studies and further examination of the release medium using SAXS. It was concluded that amiodarone is entrapped within micelles and its release is mediated via diffusion of micelles from the matrix.