Hydrate Formation of Creatine

ProUmid Application Note

Identifying of polymorphic structures, including different hydrate and anhydrous forms, is a major concern in pharmaceutical research and development.

In general, hydrates are formed by the interaction of a substance with water. The subsequent incorporation of the water molecules into the molecular structure is usually achieved by electrostatic dipole-dipole interactions, by hydrogen bonding or by coordinative binding in complexes. In crystalline hydrates, water molecules are bound in a certain stoichiometric ratio.

The different solid states often have a strong influence on the physical properties and efficiency of active pharmaceutical ingredients (API’s). For example, properties such as density, solubility, dissolution rate, hardness, melting point, mechanical strength or chemical stability can be influenced. These characteristics are important not only for the processability and handling but also for the stability and bioavailability of the products.

Application Note

Creatine occurs naturally in vertebrates, with > 90 % in the skeletal muscles as phosphocreatine. Due to its involvement in the energy metabolism, creatine – mostly as monohydrate – is one of the most used dietary supplements in sports nutrition. Here, a creatine supplementation is assumed to improve the short-term performance, maximum muscle strength and recovery.

In the case of creatine, crystallization out of an aqueous solution always results in the formation of monohydrate crystals. By drying and removing the crystallization water, the monohydrate turns into an anhydrous state.

Dynamic vapor sorption measurements are well suited to identify different hydrate states and to characterize the kinetics of hydrate formation as a function of temperature and relative humidity.

For reliable characterization, however, it is important to ensure a sufficiently high RH resolution in the critical range and an adequate equilibration time for each moisture step.