Stability solid-state

The presence of a solvent, especially water, and/or other additives or impurities, often in nonstoichiometric proportions, may modify the physical properties of a solid, often through impurity defects, through changes in crystal habit (shape) or by lowering the glass transition temperature of an amorphous solid. The effects of water on the solid-state stability of proteins and peptides and the removal of water by lyophilization to produce materials of certain crystallinity are of great practical importance although still imperfectly understood. 

Negative deviation from ideal behaviour in the solid state stabilizes the solid solution. 2so1 = -10 kJ mol-1, combined with an ideal liquid or a liquid which shows positive deviation from ideality, gives rise to a maximum in the liquidus temperature for intermediate compositions see Figures 4.10(h) and (i). Finally, negative and close to equal deviations from ideality in the liquid and solid states produces a phase diagram with a shallow minimum or maximum for the liquidus temperature, as shown in Figure 4.10(g). 

Irwin, W.J. and Iqbal, M., Solid-state stability the effect of grinding solvated excipients, Int. ]. Pharm., 75, 211,1991. 

Baxter, P. N. W. Lehn, J. M. Rissanen, K. Generation of an equilibrating collection of circular inorganic copper(I) architectures and solid-state stabilization of the dicopper helicate component. Chem. Commun. 1997,14, 1323-1324. 

Aspartame is relatively unstable in solution, undergoing cyclisation by intramolecular self-aminolysis at pH values in excess of 2.0 [91]. This follows nucleophilic attack of the free base N-terminal amino group on the phenylalanine carboxyl group resulting in the formation of 3-methylenecarboxyl-6-benzyl-2, 5-diketopiperazine (DKP). The DKP further hydrolyses to L-aspartyl-L-phenyl-alanine and to L-phenylalanine-L-aspartate [92]. Grant and co-workers [93] have extensively investigated the solid-state stability of aspartame. At elevated temperatures, dehydration followed by loss of methanol and the resultant cyclisation to DKP were observed. The solid-state reaction mechanism was described as Prout-Tompkins kinetics (via nucleation control mechanism). 

The solid state stability of indinavir sulfate has been evaluated under a variety of storage conditions and containers. For materials stored in open dishes or in double polyethylene liners within fiber containers, changes in crystallinity i.e., conversion of the crystalline etlranolate to amorphous material or to a hydrate crystal form) have been detected using XRPD or KF methods [7]. Changes in chemical purity i.e., formation of degradation products) have been detected using GC and HPLC methods... 

Strickley, R.G., and B.D. Anderson, Solid-state stability of human insulin. I. Mechanism and the effect of water on the kinetics of degradation in lyophiles from pH 2-5 solutions. Pharm Res, 1996.13(8) 1142-53. 

Fluorination and methylation have been used to synthesize975 related fluorinated nitronium ions [Eq. (4.231)]. The trifluoromethyl(methyl)nitronium ion ON(Me) CF3 + exits in the keto form in solution, but X-ray crystal structure data indicate that the enol form HON(CH2)CF3+ exists in the solid state stabilized by a hydrogen bond between the enolic OH group and one of the fluorines of the counterion. 

Matsuda, Y. and S. Kawaguchi. 1986. Physicochemical characterization of oxyphenbutazone and solid-state stability of its amorphous form under various temperature and humidity condEtlrota. 

Furlanetto et al. (26) attempted to predict and compare the solid-state stability of cefazolin sodium and cephaloridine sterile powders using data obtained at 37°C, 45°C, and 60°C. They analyzed samples for up to 6 months and found cephaloridine to be more stable than cefazolin sodium, in contrast to the relative stability of the compounds as indicated by their respective compendial storage instructions. They attributed greater stability of the cephaloridine samples to greater crystallinity compared to the cefazolin sodium samples which appeared to be mostly amorphous. Rather than comparing different samples of the same drug, this study determined the relative stability of two different drugs and compared the results to expectations based on previous information. 

Chafetz L. Practical testing of solid-state stability of pharmaceuticals. J Pharm Sci 1992 81 107. 

Byrn S. Solid State Stability of Drugs. New York Academic Press, 1982 59-75. 

Oguchi and coworkers examined the decarboxylation behavior of -aminosalicylic acid (PAS) as a freeze-dried solid under thermal stress conditions (80°C) in the presence of the excipients pullulan (a linear polysaccharide which can not form inclusion complexes with PAS) and a-cyclodextrin (39). The solid-state stability was shown to correlate with the fraction of amorphous PAS. Increasing relative amounts of pullulan resulted in higher fractions of amorphous PAS. Rapid freezing (liquid nitrogen) was shown to result in a greater relative amount of amorphous drug, as expected. 

Solid-state stability of PAS as a function of molar ratio of a-cyclodexrin (CD) to PAS was complex. At low ratios of CD to PAS, stability decreased because of inhibition of crystallization of PAS during freezing. Higher molar ratios stabilized the PAS because of formation of a crystalline inclusion complex. Again, rapid freezing resulted in higher rates of decarboxylation in the solid state. 

Herman BD, Sinclair BD, Milton N, Nail SL. The effect of bulking agent on the solid-state stability of freeze-dried methylprednisolone sodium succinate. Pharm Res 1994 11 1467-1473. 

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