Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Abstract

During pharmaceutical development processes, various investigations of physicochemical properties of a drug substance are conducted in order to guarantee the efficacy and the stability of pharmaceutical products. It is well known that the physicochemical properties of drug substances are changed by influence of water vapor under high and low relative humidity conditions. 2-4)A compound holding stoichiometric solvent molecule incorporated within the crystal lattice is designated a solvate. In particular, when the solvent is water, the compound is termed a hydrate, which is the most common solvate of drug substances.5) Because the investigation of manufacturing and formulation processes are conducted with particular attention to the behavior of drug substance hydrate, the existence of the hydrate state has a major impact on the drug development process.6) Moreover, the reduction in bioavailability may occur as the solubility of hydrate in general is lower than that of anhydrous form. 7,8) There are many studies in which the behavior of the crystal water molecule is influenced by relative humidity.9,10) A compound tends to incorporate a water molecule in the crystal structure at high relative humidities, while a hydrate may release the water molecule from the crystal at low relative humidities. It is therefore very important that the effect of relative humidity on the interconversion between the hydrate and anhydrous forms are investigated.Studies of the process of hydration and dehydration are of significance in order to predict the stability of the drug substance. Many hydrated compounds are stabilized by formation of hydrogen bonding networks between water and the drug substance molecule. A hydrated crystal is easily broken by heating and also upon storage at low relative humidities, leading to possible transformation into the anhydrous form by crystal lattice rearrangement. As a result, the drug substance may form the metastable state.Many hydrates of drug substances have been reported, for instance, carbamazepine, 11) theophylline, 12) tetracaine hydrochloride, 13) levofloxacin, 14) and diclofenac acid salts. 15)Among them, the hydrated form exists in several possible hydration states. Tetracaine hydrochloride has hemi-, mono-, and tetrahydrate states, nafagrel hydrochloride has hemi-and monohydrate states, and norfloxacin has sesqui-and pentahydrate states. 16)Sodium deoxycholate (NaDC) containing steroid skeleton is a kind of cholic acid salts. It is known that NaDC forms a micelle, 17) gel, 18) and complex 19) with drugs. It is a white powder used as a supportive solubilizing agent in pharmaceutical formulation. D'Archivio et al. suggested the possibility that NaDC was stabilized by the formation of a tetrahydrate helix structure of NaDC with the four water molecules held rigid by the formation of ion-ion, ion-dipole interactions and hydrogen bonding. 20) Vold et al. presumed the existence of NaDC octahydrate by the investigation of the solubility curve of NaDC.21) However, their findings could not sufficie...

Crystalline, liquid crystalline, and isotropic phases of sodium deoxycholate in water

“…In particular, the "as-received" sample has extra peaks at 5.5 • , 5.6 • , and 11.0 • 2θ. 21 To investigate relationships between the hydrates in more details, water sorption-desorption study was performed. Figure 8 represents water sorption-desorption isotherm, showing continuous change in water content as a function of water activity.…”

“…Overlay of XRPD patterns of NaDC crystalline hydrates: (a) literature-reported dihydrate,21 (b) literaturereported tetrahydrate,21 (c) as-received NaDC labeled by vendor as "monohydrate," (d) hydrate equilibrated at 43% RH (oversaturated potassium carbonate solution), (e) hydrate equilibrated at 23% RH (oversaturated potassium acetate solution), and (f) literature-reported octahydrate 21. Wavelength of X-ray: 1.54 Å.…”

Engineering Oral and Parenteral Amorphous Amphotericin B Formulations against Experimental Trypanosoma cruzi Infections

“…Similar results were reported by other authors. 29 The physical mixture of AmB and NaDC exhibited a double endothermic peak below 100 °C related to water loss from both AmB and NaDC. The exothermic event related to the crystallization of the amorphous anhydrous NaDC was shifted to a lower temperature (164.2 °C).…”

Polymorphism and Solvatomorphism 2005

“…Thermal analysis has been used to obtain additional information on the hydrate and anhydrate compositions of samples of commercially available magnesium stearate 134. Various hydrates of deoxycholate sodium have been studied by several physical methods as a function of their water vapor adsorption behavior 135…”