Many crystalline solids form hydrates in the presence of water. The water molecules can be incorporated into the crystal lattice in stoichiometric or non-stoichiometric proportions. Typically, a hydrate is only stable within a certain temperature and relative humidity range. Upon dehydration, a hydrate may reversible transform into an anhydrous or a less hydrated form. The hydrate form affects the physical and chemical properties of a crystalline solid such as solubility, stability and processing properties. Therefore, the hydrate form of an Active Pharmaceutical Ingredient (API) or excipient plays a significant role in the development of new drugs in connection with the bioavailability and the manufacturing process of the drug. In this context, dynamic water vapor sorption analysis enables the precise characterization of different hydrate states and their stability as a function of temperature and relative humidity. This allows new formulations, manufacturing processes and storage conditions to be adapted to specific requirements.
Hydrate formation of L-lysine HCl
Crystalline active pharmaceutical ingredients (APIs) may be present in an hydrated or, after drying, also in an anhydrous state. In pharma research and quality assurance, the characterization and control of the hydrate state is highly relevant since the properties of the active ingredient are decisively influenced by the state of hydration. This includes in particular properties such as shelf life, dissolution behavior, compressibility and bioavailability of the product. By means of DVS analysis, the different hydrate states as well as their formation kinetics and stability can be characterized as a function of relative humidity and temperature. Applications note 20-06 and white paper 20-06 demonstrate the hydrate formation of L-lysin HCl. Special focus is placed on the necessity of sufficiently long measuring times with regard to hydrate formation kinetics and the resolution of the RH steps.
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Literature references for hydrate formation analysis with the ProUmid DVS instruments
Feth, Martin P., et al. „Challenges in the development of hydrate phases as active pharmaceutical ingredients–An example.“ European Journal of Pharmaceutical Sciences 42.1 (2011): 116-129. doi:10.1016/j.ejps.2010.11.001
Kachrimanis, Kyriakos, et al. “Effects of moisture and residual solvent on the phase stability of orthorhombic paracetamol.” Pharmaceutical research 25.6 (2008): 1440-1449. doi: 10.1007/s11095-007-9529-4
D.E. Braun, U.J. Griesser, Stoichiometric and Nonstoichiometric Hydrates of Brucine, Cryst. Growth Des. (2016). doi:10.1021/acs.cgd.6b01231.
M.C. Allan, E. Grush, L.J. Mauer, RH-temperature stability diagram of α- and β-anhydrous and monohydrate lactose crystalline forms, Food Res. Int. (2020). doi:10.1016/j.foodres.2019.108717.
M. Allan, M.C. Chamberlain, L.J. Mauer, RH-Temperature Stability Diagram of the Dihydrate, β-Anhydrate, and α-Anhydrate Forms of Crystalline Trehalose, J. Food Sci. 84 (2019) 1465–1476. doi:10.1111/1750-3841.14591.