Direct detection of the crystal form of an active pharmaceutical ingredient in tablets by X-ray absorption fine structure spectroscopy.

Different crystal forms of active pharmaceutical ingredients (APIs) may display variations in physicochemical properties. During the drug development process, the definitive purpose is to maintain homogeneous quality in a single crystalline form. Hence, it is important to evaluate and understand the properties of each crystal form of APIs in pharmaceutics. In this study, forms 0, Ⅰ, Ⅱ, III of bromhexine hydrochloride, and form S of bromhexine were characterized by the commonly used methods X-ray powder diffraction, thermogravimetry-differential thermal analysis, and single crystal structure X-ray diffraction. Additionally, X-ray absorption fine structure spectroscopy (XAFS), a seldom used method in the pharmaceutics discipline was also applied to explore the chemical environment of bromine atoms in forms 0, Ⅰ, Ⅱ and S as well as chloride ions in forms 0 to Ⅱ. The XAFS spectra of each form were different from each of the other forms which indicated the chemical environment around target elements in the crystal polymorphs were distinct. Then, we measured the commercial bromhexine hydrochloride tablets with XAFS measurement and found that XAFS could distinguish the crystal form in the tablets. Hence, we demonstrated that XAFS measurements would be applicable as one of the methods for the direct detection of APIs in the tablets.

Analytical tests to evaluate pozzolanic reaction in lime stabilized soils.

Shrink-swell soils are predominant in various parts of the parts of the world. Lime has been extensively used to reduce the shrink-swell mechanism as it chemically reacts with soil minerals forming pozzolanic products such as calcite and calcium-silicate-hydrate (C-S-H). Conventionally, whether chemical treatment of soils results in effective pozzolanic stabilization reactions is determined anecdotally through engineering tests including unconfined compressive strength, plasticity index (PI), and pH tests. This study builds on existing literature regarding how more direct quantification of pozzolanic products can be obtained through tests that directly identify and quantify pozzolanic products, specifically in lime-treated clay soils. Specifically, x-ray diffraction (XRD) and differential thermogravimetric analysis (DTA) are used for this testing. Expansive soils with plasticity indices above 25% were selected for this study. Engineering tests on these lime-treated soils indicated significant improvement in strength and reduction in PI. In XRD analysis, pozzolanic products are assessed by the location and intensity of x-ray peak(s). The XRD data show a decrease in the intensity of alumio-silicate minerals such as kaolinite and smectite; silica and alumina are dissolved at a high pH and converted to pozzolanic products such as calcium-silicate-hydrate (C-S-H). DTA indicates the presence of C-S-H with the characteristic weight loss from 140°C to 250°C.The methodology describes the following: ● Sample preparation steps for XRD and DTA analysis. ● Analysis of XRD results and DTA analysis.