title: Drug-polymer miscibility across a spray dryer: a case study of naproxen and miconazole solid dispersions.
abstract: The structural and physical stability of solid dispersions have not been adequately explored during spray drying manufacturing processes. In this study a wide range of compositions of naproxen/PVP-VA 64 (poly(1-vinylpyrrolidone-co-vinyl acetate)) and miconazole/PVP-VA 64 solid dispersions prepared by different laboratory spray dryers were collected from various selected locations and used to investigate the drug-polymer mixing across spray dryers. Spray-dried dispersions with 30% (w/w) naproxen collected from the transport tube of the Pro-C-epT Microspray dryer showed the narrowest glass transition width, which apparently indicates the highest degree of drug-polymer mixing compared to the other locations. The intensity of the naproxen-PVP-VA 64 interaction peak at 1654 cm(-1) of IR spectra differs for solid dispersions (SDs) from the collector and transport tube of Pro-C-epT Microspray dryer with a higher intensity for the latter. Samples with 50% (w/w) naproxen loading collected from the cyclone and the cyclone steel part of the Buchi mini spray dryer showed a melting endotherm (Tm at 112.2 ± 0.8 °C and ΔHf between 0.7 and 1.8 J/g), whereas samples from the cyclone tube to the drying chamber were devoid of crystalline material. The variations in drug-polymer mixing extend to miconazole/PVP-VA solid dispersions where 20% drug loading showed location-dependent drug-polymer mixing. This study clearly showed that the variation in drug-polymer miscibility and solid form of the drug in solid dispersions can occur across spray dryer in small-scale manufacturing processes. The optimization of formulation parameters and spray drying process parameters is imperative to diminish these variations to enhance homogeneity of solid dispersions in laboratory scale spray dryers. The same problem can occur in geometrically large spray drying manufacturing equipment, and the robustness of the processes should be carefully assessed.
authors.affiliation: Drug Delivery and Disposition, KU Leuven , Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Zelalem Ayenew
authors.initials: ZA
authors.lastname: Worku
authors.forename: Jolie
authors.initials: J
authors.lastname: Aarts
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singh
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D008825:Miconazole / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D009288:Naproxen; D008825:Miconazole