Different drug delivery systems have been developed for peptides and proteins, with special interest on those that allow sustained parenteral release; they can prolong protein circulation, resulting in better therapeutic results and higher patient compliance. However, many of the manufacturing methods used involve conditions that can be detrimental for these molecules, such as the use of organic solvents, pH gradients, reduced pressure or heat. Besides, obtaining the desired formulation performance might be difficult since the dissolution profile might be far from optimal, or because the integrity of these bio-macromolecules cannot be preserved within the matrix. Thus, the development of these systems has followed a complex and challenging route, which have resulted in long development periods and few commercialized products. Therefore, gathering additional understanding of these systems and defining key parameters that impact the performance of them, is important to accelerate and assist the development of parenteral sustained release systems.
This work focused on the development of biodegradable implants for protein delivery, using ovalbumin (OVA) as acid-labile model protein. Hot melt extrusion (HME) was selected as the manufacturing method, since it does not involve the use of solvents and the protein can be incorporated on its more stable dry state, avoiding the creation of interfaces that compromise protein stability. Nonetheless, the use of high temperatures and presence of shear forces might impact protein stability. Therefore, the feasibility of HME to prepare OVA-loaded implants was investigated. With this purpose, a mini-ram extruder (syringe-die device) was used as a rapid screening tool. Moreover, two types of biodegradable matrices (PLGA- and lipid-based) were used to assess differences on formulation performances, with special emphasis on dissolution and protein stability.