Versatile solid modifications of icariin: structure, properties and form transformation

Abstract

A comprehensive solid-state screening experiment was performed for icariin (ICA), an active substance in Traditional Chinese Medicine (TCM) which has long been used to treat osteroporosis. Two new polymorphs in their pure forms and ten different solvate modifications were obtained and the single crystal structures were successfully determined. The isostructural phenomenon was readily observed among various organic solvates. Notably, the single crystal structure of the marketed hydrate form H1 was determined for the first time through a single crystal-single crystal transformation (SCSCT) process. The physicochemical properties of various solid forms were further studied. The results show that the newly discovered pure form α presents better thermal stability, lower hygroscopicity and higher solubility compared to the currently marketed form. The superior physicochemical properties render a better drug development ability for this widely applied TCM.

Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

“…salts, solvates and cocrystals. The formation of a new multicomponent form can significantly increase not only the solubility and thus the bioavailability, but also improve other important properties such as thermal stability, hygroscopicity, powder flowability, and physical as well as chemical stability (Qiao et al, 2011;Jia et al, 2015;Stanton & Bak, 2008). These properties are crucial in the process of drug development.…”

Formation of the First Non-Isostructural Cocrystal of Apremilast Explained

“…8 By formation of a new solid form, it is possible not only to increase the solubility, but also to improve other important physicochemical properties such as physical and chemical stability, purity, or thermal stability. 9,10 Furthermore, the scale-up process can also be simplified, if the product has the desired properties. 11 However, safety considerations of guest molecules need to be a primary concern during development of a marketable drug product.…”

“…This approach appears to be an efficient solution of the problem with drugs’ poor solubility due to the possible modifications of their physicochemical properties via the interactions between the API and the guest molecule . By formation of a new solid form, it is possible not only to increase the solubility, but also to improve other important physicochemical properties such as physical and chemical stability, purity, or thermal stability. , Furthermore, the scale-up process can also be simplified, if the product has the desired properties . However, safety considerations of guest molecules need to be a primary concern during development of a marketable drug product.…”

The Role of Solvent Composition and Polymorph Surface Chemistry in the Solution-Mediated Phase Transformation Process of Cefaclor

“…A number of researchers have attempted to identify and clarify their structural properties and transformation behaviors. [6][7][8][9][10][11] An important method for studying the formation mechanism of solvates is through solution-mediated phase transformations (SMPT) as monitored by in-or ex-situ process analytical technology. 1,7 Generally, SMPT follows Ostwald's Rule 1β , i.e.…”

“…Organic solvates form a part of the solid-form landscape examined when industry selects a suitable crystal form for subsequent formulation into a drug product. − Compared to unsolvated forms, solvates may exhibit a range of different physicochemical properties such as differences in shape, melting point, solubility, stability, dissolution rate, fluidity, and bioavailability. , There can also be significant effects on drug efficacy when solvates undergo desolvation due to changes in the temperature and humidity of the surroundings. A number of researchers have attempted to identify and clarify their structural properties and transformation behaviors. − …”