scholarly journals Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Crystals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1440
Author(s):  
Yanan Wang ◽  
Yong Wang ◽  
Jin Cheng ◽  
Haibiao Chen ◽  
Jia Xu ◽  
...  

The amorphous form of a drug usually exhibits higher solubility, faster dissolution rate, and improved oral bioavailability in comparison to its crystalline forms. However, the amorphous forms are thermodynamically unstable and tend to transform into a more stable crystalline form, thus losing their advantages. In order to investigate and suppress the crystallization, it is vital to closely monitor the drug solids during the preparation, storage, and application processes. A list of advanced techniques—including optical microscopy, surface grating decay, solid-state nuclear magnetic resonance, broadband dielectric spectroscopy—have been applied to characterize the physicochemical properties of amorphous pharmaceutical solids, to provide in-depth understanding on the crystallization mechanism. This review briefly summarizes these characterization techniques and highlights their recent advances, so as to provide an up-to-date reference to the available tools in the development of amorphous drugs.

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5318
Author(s):  
Szymon Sip ◽  
Natalia Rosiak ◽  
Andrzej Miklaszewski ◽  
Patrycja Talarska ◽  
Ewa Dudziec ◽  
...  

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-β-cyclodextrin, Pluronic® F-127, and Soluplus®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the “halo effect” on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10−6 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-β-cyclodextrin, Pluronic® F-127, and Soluplus®), although in their cases, the values of apparent constants permeability were decreased.


2021 ◽  
Vol 14 (5) ◽  
pp. 453
Author(s):  
Gabriela Wiergowska ◽  
Dominika Ludowicz ◽  
Kamil Wdowiak ◽  
Andrzej Miklaszewski ◽  
Kornelia Lewandowska ◽  
...  

To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients—hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)—were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques—X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (Papp crystalline VAR = 6.83 × 10−6 cm/s vs. Papp amorphous VAR = 8.75 × 10−6 cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5—more than 1.5-fold increase (Papp amorphous VAR = 8.75 × 10−6 cm/s vs. Papp amorphous VAR:β-CD 1:5 = 13.43 × 10−6 cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and β-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect.


2021 ◽  
Vol 54 (5) ◽  
Author(s):  
Qin Shi ◽  
Fang Li ◽  
Jia Xu ◽  
Lingling Wu ◽  
Junbo Xin ◽  
...  

Physical stability is one of the main challenges when developing robust amorphous pharmaceutical formulations. This article reports fast crystal growth behaviors of the γ and α forms of indomethacin (IMC) initiated by bubbles in the interior of a supercooled liquid. Bubble-induced crystal growth of γ-IMC exhibits approximately the same kinetics as its surface crystal growth, supporting the view that bubble-induced crystal growth is a surface-facilitated process. In contrast, the rates of bubble-induced crystal growth of α-IMC are much faster than those of its surface crystal growth. These results indicate that the bubble-induced crystal growth not only depends on the interface created by the bubble but also strongly correlates with the true cavitation of the bubble. Moreover, bubble-induced fast crystal growth of γ- and α-IMC can be terminated at different temperatures by cooling. These outcomes are meaningful for the in-depth understanding of physical stability and pre-formulation study of amorphous pharmaceutical solids showing surface-facilitated crystal growth.


Cerâmica ◽  
2013 ◽  
Vol 59 (352) ◽  
pp. 576-587 ◽  
Author(s):  
A. J. Schwanke ◽  
S. B. C. Pergher

Porous heterostructured clays - PCHs - are lamellar solids with acid and adsorptive properties serving as catalysts or catalyst supports formed on a template mechanism. This work provides information about porous heterostructured clays. Historical aspects of the development of lamellar solids to porous heterostructured clays will be discussed, and detailed information on synthesis and applicationaspects, as well as on the influence of eachreagent on these materials and the characterization techniques used to prove their formation will be given.


2021 ◽  
Vol 83 (2) ◽  
pp. 77-83
Author(s):  
Yudi Wicaksono ◽  
Viddy Agustian Rosidi ◽  
Sri Yessika Saragih ◽  
Lyta Septi Fauziah ◽  
Dwi Setyawan

Atorvastatin calcium (AC) is a statin drug used to lower cholesterol. Its crystalline form is usually found in the market with low solubility properties. The amorphization of crystalline AC is a technique used to increase its solubility however; the amorphous form has less thermodynamic stability. Therefore, to increase the solubility properties of its crystalline form, an AC coamorphous solid was prepared. This coamorphous solid was prepared using spray drying techniques, and coformers such as isonicotinamide (INA) and maleic acid (MA). Furthermore, characterization was carried out using powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy, and scanning electron microscopy, while the solubility properties test was conducted using the shake-flask and paddle method. The results showed that the spray-dried solids were coamorphous with single-phase homogeneous systems. Furthermore, the coamorphous solids, AC-INA and AC-MA were found to have a higher Tg than the melting points of other components, and formed intermolecular interactions between them. The higher Tg and presence of intermolecular interactions indicate that coamorphous solids are more stable than the amorphous form. Therefore, the results of the solubility and dissolution test showed that the coamorphous solid of AC-INA and AC-MA have better solubility properties compared to the AC crystalline form.


In a former paper, printed in the Philosophical Transactions for the year 1798, Count de Bournon gave an analytical description of the crystalline forms of corundum from the East Indies and from China. From a note inserted at the beginning of the present com­munication, we learn, that the great number of specimens of that substance, since collected from different parts, chiefly of the East, have added so considerably to our knowledge relating to that sub­ject, as to render it necessary not only to correct, but even, in many respects, to alter our opinion concerning it : and that hence, rather than create intricacy by introducing this additional knowledge in the form of a supplement, he had thought it expedient to collect all the information that could be obtained into one point of view, in hopes of delivering, in the present paper, with the addition of a chemical analysis which we are taught to expect from Mr. Chenevix, a com­plete mineralogical history of this curious substance. The paper is prefaced by a short historical account of the opinions of former naturalists concerning the corundum stone, and its classi­fication in the mineral system. The first of these, who derived their knowledge chiefly from lapidaries, had no hesitation in placing it among the gems, the hardest of which they distinguished by the epithet Oriental, and subdivided them according to their colours. Romé de Lisle was the first who deduced distinctive characters from the crystalline forms of the different sorts, rejecting the colour as a fallacious character. The first chemists who undertook to analyse this stone, thought themselves authorized to consider it as consisting of new elementary earths; but afterwards it was thought, and it appears now with much reason, to belong to the class of those stones which are chiefly, if not entirely, composed of argill. Werner at length also undertook the analysis; but he retrograded somewhat from what has been since found to be the truth, by placing it between pitch-stone and felspar. Abbé Hauy at length, recurring again to the crystalline form, placed it immediately after felspar, and before the Ceylonite; from both which, however, it differs widely, both by its hardness and specific gravity.


Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10544-10578 ◽  
Author(s):  
Shaodong Sun ◽  
Shuhua Liang

In this review, we selectively summarize the recent advances in mesoporous g-C3N4(mpg-C3N4), including synthesis strategies, characterization techniques, fundamental properties, functional modifications and potential applications. Several difficulties and emerging issues are also proposed.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Karim Samy El-Said ◽  
Ehab Mostafa Ali ◽  
Koki Kanehira ◽  
Akiyoshi Taniguchi

Titanium dioxide nanoparticles (TiO2NPs) are manufactured worldwide for use in a wide range of applications. There are two common crystalline forms of TiO2anatase and rutile with different physical and chemical characteristics. We previously demonstrated that an increased DNA damage response is mediated by anatase crystalline form compared to rutile. In the present study, we conjugated TiO2NPs with polyethylene glycol (PEG) in order to reduce the genotoxicity and we evaluated some oxidative stress parameters to obtain information on the cellular mechanisms of DNA damage that operate in response to TiO2NPs different crystalline forms exposure in hepatocarcinoma cell lines (HepG2). Our results indicated a significant increase in oxidative stress mediated by the anatase form of TiO2NPs compared to rutile form. On the other hand, PEG modified TiO2NPs showed a significant decrease in oxidative stress as compared to TiO2NPs. These data suggested that the genotoxic potential of TiO2NPs varies with crystalline form and surface modification.


Sign in / Sign up

Export Citation Format

Share Document