title: Melt extrusion vs. spray drying: The effect of processing methods on crystalline content of naproxen-povidone formulations.
abstract: Our hypothesis is that melt extrusion is a more suitable processing method than spray drying to prepare amorphous solid dispersions of drugs with a high crystallization tendency. Naproxen-povidone K25 was used as the model system in this study. Naproxen-povidone K25 solid dispersions at 30% and 60% drug loadings were characterized by modulated DSC, powder X-ray diffraction, FT-IR, and solid-state13C NMR to identify phase separation and drug recrystallization during processing and storage. At 30% drug loading, hydrogen bond (H-bond) sites of povidone K25 were not saturated and the glass transition (Tg) temperature of the formulation was higher. As a result, both melt-extruded and spray-dried materials were amorphous initially and remained so after storage at 40°C. At 60% drug loading, H-bond sites were saturated, and Tgwas low. We were not able to prepare amorphous materials. The initial crystallinity of the formulations was 0.4%±0.2% and 5.6%±0.6%, and increased to 2.7%±0.3% and 21.6%±1.0% for melt-extruded and spray-dried materials, respectively. Spray-dried material was more susceptible to re-crystallization during processing, due to the high diffusivity of naproxen molecules in the formulation matrix and lack of kinetic stabilization from polymer solution. A larger number of crystalline nucleation sites and high surface area made the spray-dried material more susceptible to recrystallization during storage. This study demonstrated the unique advantages of melt extrusion over spray drying for the preparation of amorphous solid dispersions of naproxen at high drug level.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors.forename: Abbe
authors.initials: A
authors.lastname: Haser
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors.forename: Tu
authors.initials: T
authors.lastname: Cao
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94040, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Lubach
authors.affiliation: Foster Delivery Sciences, 45 Ridge Road, Putnam, CT 06260, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Listro
authors.affiliation: Foster Delivery Sciences, 45 Ridge Road, Putnam, CT 06260, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Acquarulo
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA. Electronic address: feng.zhang@austin.utexas.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D003890:Desiccation; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D009288:Naproxen / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D033362:Powder Diffraction; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D011205:Povidone
keywords: Amorphous solid dispersion; Melt extrusion; Naproxen; Recrystallization; Spray drying