Different molecular motions in lyophilized protein formulations as determined by laboratory and rotating frame spin‐lattice relaxation times

Abstract

The spin‐lattice relaxation times in the laboratory and rotating frame (T1 and T1ρ) of protons and carbons in lyophilized bovine serum γ‐globulin formulation containing dextran were determined by 1H solid‐state pulsed nuclear magnetic resonance (NMR) and high‐resolution 13C solid‐state NMR. The temperature dependence of T1 and T1ρ of dextran protons in the lyophilized formulation suggests that the correlation time, τc, of the methylene protons in dextran is ∼10−6 s at −100°C and 60% relative humidity, and decreases to 10−7 s at 0°C. When temperature is increased from 0°C, the increased motion of the methylene groups is reflected in T1, but is too fast to be observed by changes in T1ρ. Thus, the motion of the methine groups rather than the methylene groups begins to be reflected in T1ρ. The correlation time of the methine protons as determined by T1ρ was of the same order as that of the methine carbons as determined by T1ρ. As the temperature is increased past the glass/rubber transition temperature, both the methylene and methine motions are greatly enhanced, resulting in much shorter T1 and T1ρ relaxation times. © 2002 Wiley‐Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2203–2210, 2002