Solvent-Assisted Secondary Drying of Spray-Dried Polymers
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RESEARCH PAPER
Solvent-Assisted Secondary Drying of Spray-Dried Polymers Kimberly B. Shepard 1 & April M. Dower 2 & Alyssa M. Ekdahl 3 & Michael M. Morgen 1 & John M. Baumann 1 & David T. Vodak 1
Received: 11 June 2020 / Accepted: 22 July 2020 # The Author(s) 2020
ABSTRACT Purpose The purpose of this work is to introduce solventassisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spraydrying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spraydrying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondarydrying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time. Methods Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11095-020-02890-0) contains supplementary material, which is available to authorized users. * Kimberly B. Shepard [email protected]
1
Research & Development, Lonza Pharma, Biotech and Nutrition, Bend, Oregon, USA
2
Product Development, Lonza Pharma, Biotech and Nutrition, Bend, Oregon, USA
3
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA
Results Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods. Conclusions The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.
KEY WORDS amorphous solid dispersion . diffusion . eudragit L100 . secondary drying . spray-drying
ABBREVIATIONS API CAP DMAC DSC DVS GC HPMCAS ICH ID KF PMMAMA RH RS SCFH SDD SEM THF Tbubbler Tdrying Tg Tin Tout
Active pharmaceutical ingredient Cellulose acetate phthalate Dimethylacetamide Differential scanning calorimetry Dynamic vapor sorption Gas chromatography Hydroxypropyl methylcellulose acetate succinate International Conference on Harmonization Inner diameter Karl Fischer Poly(methyl methacrylate-co-methacrylic acid), trade name Eudragit® L100 Relative humidity Relative saturation Standard cubic feet per hour Spray-dried dispersion Scanning electron m
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