title: Improving the API dissolution rate during pharmaceutical hot-melt extrusion I: Effect of the API particle size, and the co-rotating, twin-screw extruder screw configuration on the API dissolution rate.
abstract: The dissolution rate of the active pharmaceutical ingredients in pharmaceutical hot-melt extrusion is the most critical elementary step during the extrusion of amorphous solid solutions - total dissolution has to be achieved within the short residence time in the extruder. Dissolution and dissolution rates are affected by process, material and equipment variables. In this work, we examine the effect of one of the material variables and one of the equipment variables, namely, the API particle size and extruder screw configuration on the API dissolution rate, in a co-rotating, twin-screw extruder. By rapidly removing the extruder screws from the barrel after achieving a steady state, we collected samples along the length of the extruder screws that were characterized by polarized optical microscopy (POM) and differential scanning calorimetry (DSC) to determine the amount of undissolved API. Analyses of samples indicate that reduction of particle size of the API and appropriate selection of screw design can markedly improve the dissolution rate of the API during extrusion. In addition, angle of repose measurements and light microscopy images show that the reduction of particle size of the API can improve the flowability of the physical mixture feed and the adhesiveness between its components, respectively, through dry coating of the polymer particles by the API particles.
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA; Polymer Processing Institute, Newark, NJ 07102, USA.
authors.forename: Costas G
authors.initials: CG
authors.lastname: Gogos
authors.affiliation: Polymer Processing Institute, Newark, NJ 07102, USA. Electronic address: nikolaos.ioannidis@polymers-ppi.org.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ioannidis
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D005079:Excipients / Q000737:chemistry; D006358:Hot Temperature; D008859:Microscopy, Polarization; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D005079:Excipients; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D000082:Acetaminophen; D011092:Polyethylene Glycols
keywords: Amorphous solid dispersions; Dissolution rate; Flowability; Hot-melt extrusion; Particle size; Screw configuration