Release pathways of interferon α2a molecules from lipid twin screw extrudates revealed by single molecule fluorescence microscopy

Solvent-Free Melting Techniques for the Preparation of Lipid-Based Solid Oral Formulations

“…In a second study with lysozyme Sax and Winter chose different low melting lipids in the combination with Dynasan 118 and different portions of pore forming agent to analyze the influence on the release kinetics of protein molecules from the lipid implant ( 45 ). The partial melting of the low melting fraction at incubation temperatures of 37°C built a protein reservoir and an additional non-aqueous diffusion pathway besides the conventional way through the buffer filled interconnected pore-network created by the dissolution of hydrophilic excipients ( 45 , 165 ). Recently, Oliveira et al evaluated the extrudability of formulations, comprising Gelucire 33/01 and two further lipid excipients such as Dynasan 114, Precirol ATO 5, Witocan 42/44 or Compritol 888 ATO at room temperature and revealed a complex influence on porosity, thermal behavior, mechanical properties and dissolution rate depending on the chosen composition ( 307 ).…”

Implants as Sustained Release Delivery Devices for Vaccine Antigens

“…The resulting extrudates often have a slightly larger diameter than the die, a phenomenon referred to as "die swell" where the sudden drop in pressure causes the polymer to show stress relaxation. In the pharmaceutical context, twin-screw extrusion has been used successfully for the preparation of implants from triglycerides and mixtures of triglycerides for the delivery of drugs and proteins (Reitz and Kleinebudde 2007 ;Schulze and Winter 2009 ;Sax et al 2012a ). Twin-screw extrudates have been prepared containing IFN-α-2a Sax et al 2012a ) and lysozyme (Schwab et al 2009 ;Sax and Winter 2012 ).…”

“…In the pharmaceutical context, twin-screw extrusion has been used successfully for the preparation of implants from triglycerides and mixtures of triglycerides for the delivery of drugs and proteins (Reitz and Kleinebudde 2007 ;Schulze and Winter 2009 ;Sax et al 2012a ). Twin-screw extrudates have been prepared containing IFN-α-2a Sax et al 2012a ) and lysozyme (Schwab et al 2009 ;Sax and Winter 2012 ). However, this method has not been utilized for the preparation of implants for vaccine delivery where the implants have a much lower protein/peptide load (5 mg in drug delivery vs. 1-50 μg for vaccines).…”

Mechanistic studies on the release of lysozyme from twin-screw extruded lipid implants

“…The results became recently available and have been published [32]. The authors conclude that by the choice of a suitable implant composition long-term protein drug release from tsc-extrudates with subsequent biodegradation of the triglyceride matrix material is feasible in-vivo.…”