Probing the Distribution of Water in a Multi-Component System by Solid-State NMR Spectroscopy.
To characterize the distribution of water among various components in a powder blend using solid-state NMR spectroscopy.



Water sorption behavior of theophylline anhydrate and excipients was determined by dynamic vapor sorption (DVS) and Karl Fischer Titration (KFT) after storing them in humidity chambers for 1 week at room temperature (RT) and calibration curves were generated for water content vs. (1)H T 1 relaxation times. Powder blends (either with microcrystalline cellulose or lactose as diluent) were stored at different relative humidity (RH) conditions and analyzed periodically using solid-state NMR, powder X-ray diffraction, and KFT.



Anhydrous theophylline converted to the hydrate at ≥ 84% RH. Based on the calibration curves of water content vs. relaxation times, the distribution of water in the powder blends was estimated. The total water content calculated using ssNMR was in good agreement with values measured using KFT. In blends stored at 90% RH, theophylline anhydrate-to-hydrate conversion did not occur in 1 week.



The distribution of water in multi-component powder blends was successfully determined using correlation between (1)H T 1 relaxation times and total water content. Excipient water sorption inhibited hydrate formation in theophylline at 90% RH. Water distribution was affected by excipient type. The extent of water sorbed by excipients in blends was found to be different than their standalone equilibrium water content.
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55414, USA.
Pinal
P
Mistry
Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, Mailstop 432a, South San Francisco, California, 94080, USA.
Paroma
P
Chakravarty
Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, Mailstop 432a, South San Francisco, California, 94080, USA. lubach.joseph@gene.com.
Joseph W
JW
Lubach
D001993:Bronchodilator Agents / Q000032:analysis / Q000378:metabolism; D005079:Excipients / Q000032:analysis / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013806:Theophylline / Q000032:analysis / Q000378:metabolism*; D014867:Water / Q000032:analysis / Q000378:metabolism*; D014961:X-Ray Diffraction / Q000379:methods
D001993:Bronchodilator Agents; D005079:Excipients; D014867:Water; D013806:Theophylline
formulation; hydrate; solid-state NMR; theophylline; water distribution