Probing the Distribution of Water in a Multi-Component System by Solid-State NMR Spectroscopy

• Published in: Pharmaceutical research Vol. 33; no. 10; pp. 2470 - 2480
• Main Authors: Mistry, Pinal, Chakravarty, Paroma, Lubach, Joseph W.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2016; Springer; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Bronchodilator Agents - analysis; Bronchodilator Agents - metabolism; Cellulose; Diffraction; Excipients - analysis; Excipients - metabolism; Humidity; Investigations; Lactose; Magnetic Resonance Spectroscopy - methods; Medical Law; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Pharmacology/Toxicology; Pharmacy; Powders; Research Paper; Spectrum analysis; Theophylline; Theophylline - analysis; Theophylline - metabolism; Water; Water - analysis; Water - metabolism; X-Ray Diffraction - methods; X-rays; formulation; solid-state NMR; hydrate; theophylline; water distribution
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-016-1972-7

Purpose To characterize the distribution of water among various components in a powder blend using solid-state NMR spectroscopy. Methods 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. Results 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. Conclusions 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.