Hybrid matrix systems for oral controlled drug delivery

Taking into consideration the problems of patients compliance related to the statins side effects, the starting point of the present thesis work has been the assumption that a suitable controlled release formulation for the oral delivery of statins would be of great value to improve the efficacy of the clinical therapy. In fact, the myopathy associated with the statins treatment has been attributed to both patient characteristics (age, gender, renal and hepatic functionality, diet) and statins properties (lipophilicity, high absorption, limited protein binding). The combination of these two aspects eventually may lead to patient drop out from therapy. Given these premises, an ideal dosage form for statins administration would be characterized by a drug delivery rate and subsequent intestinal absorption rate perfectly synchronized with the drug empathic uptake and metabolism. In this way, the systemic exposure to the statin would be minimized or even made equal to zero. Thus the side effects, that are related to statin plasma concentration, would be avoided and the patient compliance increased. Therefore, the aim of the present doctorate project was to design and develop innovative formulations for controlled oral delivery of high doses simvastatin taken as a model compound of this class of drugs and characterized by high lipophilicity and good permeability. The project was carried by investigating ternary hybrid matrices constituted of hydrophilic polymers and a solid lipid excipient. An addition goal was the investigation of the mechanism behind the drug release from such ternary systems, which has obtained little attention in the available literature. A further aim has been the study of the suitability of hot melt extrusion as a technique fir large-scale production of the matrices here developed. This final part of the project has been carried out at the University of Toronto (Canada) under the supervision of Prof. Ping I. Lee.