Effect of process variables on the Small and Wide Angle X-ray Scattering (SWAXS) patterns of powders, granules and pharmaceutical tablets

Hodžić, Aden; Llusa, Marcos; Heigl, Nicolas; Tritthart, Walter; Fraser, Simon D.; Laggner, Peter; Khinast, Johannes G.

doi:10.1016/j.powtec.2012.01.043

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…Further insight both into the API content and the structure in the solid state can be obtained by off-line methods, and X-ray scattering techniques are ideal for this purpose. Thus, small and wide angle X-ray scattering techniques (SWAXS) have been used to assess the API and excipient content (20), to investigate the effects of process variables on the crystalline state of powders, granules and tablets (21) and to study interactions between the model's membranes and biologically active compounds (22,23). This paper describes in-line crystallization monitoring of the drug entacapone via Raman spectroscopy and multivariate methods involving principal components analysis (PCA) and indirect hard modeling (IHM) as well as off-line characterization of the obtained polymorphic forms using Raman spectroscopy and SWAXS.…”

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confidence: 99%

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Jednačak¹,

Hodžić²,

Scheibelhofer³

et al. 2014

Acta Pharmaceutica

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Many active pharmaceutical ingredients (APIs) are small organic molecules that have different polymorphic forms (1). It is well known that the API's polymorphic form can affect its physico-chemical properties, such as density, melting point, solubility, stability, morphology and bioavailability (2). Thus, polymorphic screening is a critical part of preformulation studies. The search for possible polymorphic forms typically begins with crystallization of a drug substance from various solvents, including those frequently used during the final crystallization steps (3, 4). Since the API's physicochemical properties can have a dramatic impact on its therapeutic effect, it is crucial to detect the polymorphic form with the characteristics appropriate for the intended use. For this purpose, the parameters affecting the crystallization process should be controlled and optimized (5). Major limitations to improving the control of crystallization parameters Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

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confidence: 99%

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Jednačak¹,

Hodžić²,

Scheibelhofer³

et al. 2014

Acta Pharmaceutica

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“…A deeper insight into products’ mesoporous structure can be obtained by porosimetry, such as BET analysis, and the analytical modeling of the SAXS data by applying the Guinier–Porod law. In addition, the Guinier–Porod law applied on SAXS data allows extracting the real-space information contained in the scattering curves [ 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

KIT-5-Assisted Synthesis of Mesoporous SnO2 for High-Performance Humidity Sensors with a Swift Response/Recovery Speed

et al. 2023

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Developing highly efficient semiconductor metal oxide (SMOX) sensors capable of accurate and fast responses to environmental humidity is still a challenging task. In addition to a not so pronounced sensitivity to relative humidity change, most of the SMOXs cannot meet the criteria of real-time humidity sensing due to their long response/recovery time. The way to tackle this problem is to control adsorption/desorption processes, i.e., water-vapor molecular dynamics, over the sensor’s active layer through the powder and pore morphology design. With this in mind, a KIT-5-mediated synthesis was used to achieve mesoporous tin (IV) oxide replica (SnO2-R) with controlled pore size and ordering through template inversion and compared with a sol-gel synthesized powder (SnO2-SG). Unlike SnO2-SG, SnO2-R possessed a high specific surface area and quite an open pore structure, similar to the KIT-5, as observed by TEM, BET and SWAXS analyses. According to TEM, SnO2-R consisted of fine-grained globular particles and some percent of exaggerated, grown twinned crystals. The distinctive morphology of the SnO2-R-based sensor, with its specific pore structure and an increased number of oxygen-related defects associated with the powder preparation process and detected at the sensor surface by XPS analysis, contributed to excellent humidity sensing performances at room temperature, comprised of a low hysteresis error (3.7%), sensitivity of 406.8 kΩ/RH% and swift response/recovery speed (4 s/6 s).

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“…The quality of medicines, particularly their crystalline purity in the solid state or polymorphism, is very important to pharmaceutical products and their actual efficacy [ 1 ]. To test and detect this in a timely manner, various well-known analytical methods are used.…”

Section: Introductionmentioning

confidence: 99%

“…Prices and purity play an important role, especially when choosing a supplier. The API quality and crystalline purity must be satisfied, otherwise the final product not only causes manufacturing problems (e.g., tableting or dissolution, stability) [ 1 , 2 , 3 ] but can also induce possible therapeutic side effects. It is generally known that several processes (e.g., high-energy milling) can alter the crystalline state of an unstable API.…”

Section: Introductionmentioning

confidence: 99%

Small-Angle X-ray Scattering (SAXS) Used for the Identification of Nicomorphine Polymorphic Changes at the Early Stage to Avoid Varied Stability and Possible Side Effects

Malanovic,

Birarda,

Eder

et al. 2024

Pharmaceuticals

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In this paper, we present the identification of polymorphisms at an early stage, identified by applying non-standard methods such as SAXS. We provide an analytical approach to polymorphism in the quality/purity of an active pharmaceutical ingredient (API), supplied to a generic company by two different suppliers (i.e., manufacturers). Changes in thermodynamic polymorphism firstly become visible in traces in the larger crystal lattices, which are visible on the SAXS spectrum only using the logarithmic scale, as shown in the result figures. Hence, we are here on the trail of the beginning of a new polymorph in nicomorphine, whose crystal waviness at the early stage is visible only in the additional symmetrical peaks identified and calculated using SAXS, while the chemical analyses excluded all kinds of chemical impurities. The chemical and structural properties were studied using the following techniques: SAXS, WAXS, DSC, dissolution, Raman spectroscopy, and FTIR. Only the SAXS technique could identify crucial differences and calculate the additional signals related to giant crystals, whilst a standard method such as WAXS showed none, and nor did the chemical analyses, such as Raman spectroscopy and FT-IR. This means that due to water in crystallization (known in nicomorphine) or thermodynamic waviness, the formation of the new polymorph starts first in traces, which become visible at larger distances from the crystal lattice, detectible only in the SAXS range. This is a very important premise and hypothesis for further research, and we believe that this work lays a new stone in understanding the origin of new unknown polymorphs and their mixtures. Therefore, the aim of this work is to show that the use of non-standard methods (i.e., SAXS) can be of great benefit to API analysis and the identification of polymorphic changes in the early phase, which can cause varied stability, solubility and bioavailability and thus different therapeutic effects or side effects.

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Effect of process variables on the Small and Wide Angle X-ray Scattering (SWAXS) patterns of powders, granules and pharmaceutical tablets

Cited by 7 publications

References 33 publications

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

KIT-5-Assisted Synthesis of Mesoporous SnO2 for High-Performance Humidity Sensors with a Swift Response/Recovery Speed

Small-Angle X-ray Scattering (SAXS) Used for the Identification of Nicomorphine Polymorphic Changes at the Early Stage to Avoid Varied Stability and Possible Side Effects

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