Crystal growth and structure of a new hormonal derived compound.

The 17alpha-acetoxy-6-hydroxymethyl-3,20-dioxo-19-nor-pregna-4,6-diene (C(23)H(30)O(5)), a new hormonal derived compound presenting a potential therapeutic interest for a pharmaceutical formulation, raises a problem as it precipitates spontaneously when in contact with an aqueous solution. The solubilization of this potential pharmaceutical drug was investigated to control and/or prevent crystal formation in the presence of water. The solubility limit of this potential drug, either in Cremophor(R) EL or RH40, was determined to be 2.6% (w/w). In addition, crystal growth of this compound solubilized in Cremophor(R) and in contact with aqueous environment was undertaken to improve crystal quality and size and subsequently to determine its three dimensional structure. We used a system that allows slow single crystal growth at room temperature. The crystallization system that we set-up comprised an interface between two solutions: one containing the compound solubilized either in Cremophor(R) RH40 or EL and the other containing water and glycine. The crystal structure was established by single crystal X-ray diffraction analysis. The structure refinement study revealed the presence of one water molecule with strong intermolecular hydrogen bonding leading to an atomic arrangement corresponding to an infinite chain in the [001] direction.

In vitro studies on the influence of carbomers on the availability and acceptability of estradiol gels.

The objective of the present study was to evaluate the pharmaceutical properties of estradiol (CAS 50-28-2) gels: pH, viscosity, texture, spreadability, evaporation of solvent and transcutaneous diffusion from carbomer-based formulations. This study was performed with the aim of measuring possible pharmaceutical differences as a function of the nature of the polymers used. The results obtained show a similarity of behaviour for the Estreva gels made with carbomers Carbopol 1342 (C 1342) and 1382 (C 1382). The reference gel, commercially available in France and made with the carbomer Carbopol 934 (C 934) is different in terms of its rheological criteria.