Processing of Polymeric Dosage Forms for Advanced Drug Delivery: From Melt-Extrudates to Nanoparticles

Abstract

Pharmaceutical technology has been directed towards solving the challenges brought by changes in drug discovery characterized by the advent, on the one hand, of sparingly water-soluble drugs exhibiting low oral bioavailability and, on the other, by the so-called biopharmaceuticals, namely peptide and protein drugs as well as nucleic acid materials. The article reviews some of the results obtained in the laboratory in connection with oral and parenteral drug delivery. Hot-melt extrudates for oral administration appear to be very efficient for the sustained release of highly water-soluble drugs, whereas pH-sensitive nanoparticles have proved very beneficial for increasing the bioavailability of protease inhibitors. Special attention is also paid to the scaling up aspect of the nanoparticle preparation methods. As for the parenteral route, biodegradable implants and nanoparticles are examined for their potential to extend drug action. The important issue of premature degradation of peptide or protein drugs during manufacturing of particles is also addressed using tetracosactide and insulin as model drugs. In this respect, emphasis is put on the use of MALDI-TOF MS for the direct assessment of the primary structure of proteins such as insulin in nanoparticles and simultaneous quantification. Finally, various means for preventing rapid clearance of colloidal carriers from the bloodstream by the reticuloendothelial system are described, in particular the utilization of pegylated biodegradable polymers. The reduction of nanoparticle phagocytosis opens perspectives for improved drug targeting of organs.

Keywords

• Controlled drug release
• Drug delivery systems
• Drug targeting
• Extrudates
• Hot-melt extrusion
• Implants