scholarly journals Reliable Characterization of Organic & Pharmaceutical Compounds with High Resolution Monochromated EEL Spectroscopy

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1434
Author(s):  
Partha Pratim Das ◽  
Giulio Guzzinati ◽  
Catalina Coll ◽  
Alejandro Gomez Perez ◽  
Stavros Nicolopoulos ◽  
...  
Keyword(s):  
Organic Compounds ◽  
Drug Product ◽  
Amorphous Solid ◽  
High Energy ◽  
New Drugs ◽  
High Energy Resolution ◽  
Amorphous Solid Dispersion ◽  
Pharmaceutical Ingredients ◽  
Transmission Electron ◽  
Optical Region

Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion—ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized.

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

Development of an in vivo -relevant drug product performance method for an amorphous solid dispersion

2017 ◽  
Vol 142 ◽  
pp. 307-314 ◽  
Author(s):  
Brian W. Pack ◽  
Yelizaveta Babayan ◽  
Mark A. Schrad ◽  
Paul A. Stroud ◽  
David C. Sperry ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Drug Product ◽  
Amorphous Solid ◽  
Product Performance ◽  
Amorphous Solid Dispersion

scholarly journals Evaluating the effect of the porous and non-porous colloidal silicon dioxide as a stabilizer on amorphous solid dispersion

2020 ◽  
Vol 10 (5) ◽  
pp. 255-263
Author(s):  
Smruti P. Chaudhari ◽  
Mittal Bhadiyadra ◽  
Rutesh H. Dave
Keyword(s):  
Silicon Dioxide ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Water Solubility ◽  
High Surface ◽  
Amorphous Solid ◽  
Energy System ◽  
High Energy ◽  
Amorphous Solid Dispersion ◽  
The Stability

Advancement in the discovery of drugs has led to many highly lipophilic compounds with very low water solubility. Amorphous solid dispersion is one of the emerging technologies to increase the solubility of these drugs. The stability of these systems is critical since the high energy system tends to recrystallize, which negates the benefits of these systems. In this paper, we are evaluating the use of colloidal silicon dioxide as a potential stabilizer to stabilize the amorphous solid dispersions. Two types of colloidal silicon dioxide are used: porous colloidal silicon dioxide -Syloid 244 Fp and nonporous fumed silica – Aerosil 200. These silicon dioxides have a high surface area. Two methods of incorporation are used to incorporate silicon dioxide into the solid dispersion. The spray drying method is used to make amorphous solid dispersion. It was found that porous silicon dioxide is better to increase stability as well as increasing dissolution rate and % release of the drug. The addition of silicon dioxide internally to the dispersion increases the dissolution rate, and the addition of silicon dioxide externally increases the stability of the solid dispersion. Keywords: colloidal silicon dioxide, stabilizer, amorphous solid dispersion, low water solubility

scholarly journals A Review on Significance of Identifying an Appropriate Solid Form Duringdrug Discovery and Product Development

2021 ◽  
Vol 18 (2) ◽  
pp. 154-170
Author(s):  
Nishadh A. Patel
Keyword(s):  
Product Development ◽  
Process Development ◽  
Drug Product ◽  
Analytical Data ◽  
Physical Stability ◽  
Analytical Techniques ◽  
Amorphous Solid ◽  
Drug Candidate ◽  
Amorphous Solid Dispersion ◽  
Solid Form

In recent years, solid form screening has become an integral and mandatory part of drug development. Solid form screening typically involves producing and characterizingmaximum possible solid forms of a potential drug candidate. Different types of solid forms for future drug product development includes salt screening, co-crystal screening, crystallization process development, polymorph screening as well as amorphous solid dispersion screening.Screening studies of a solid form is a set of carefully designed experiments that requires use of advanced analytical techniques to collect analytical data followed by a thoughtful data analysis.This solid form screening studies guide an important decision-making of lead solid form whichis likely to play a vital role during the pharmaceutical product development lifecycle. The selection criteria include pharmaceutically relevant properties, such as therapeutic efficacy and processing characteristics as well as role of physicochemical properties (i.e. solubility, dissolution rate, hygroscopicity, physical stability and chemical purity) in drug product development. A selected solid form, if thermodynamically unstable, it may undergo solid form changes upon exposure to environmental conditions such as temperature and relative humidity as well as manufacturing stress during the pharmaceutical unit operations. In thepresent work, fundamentals of solid form screening are discussed, including the experimental screening methodologies as well as characterization and analysis of solid forms. The importance of drug product risk assessment pertaining to the desired solid form are also discussed here.

A Wien Filter Electron Energy Loss Spectrometer for Transmission Electron Microscopy

1990 ◽  
Vol 48 (2) ◽  
pp. 32-33
Author(s):  
K. Tsuno ◽  
J. Ohyama ◽  
M. Kato ◽  
J. Kimura ◽  
M. Kai ◽  
...  
Keyword(s):  
Imaging System ◽  
Optical Axis ◽  
Detection System ◽  
High Energy ◽  
High Energy Resolution ◽  
Wien Filter ◽  
Magnetic Forces ◽  
Transmission Electron ◽  
Electron Energy Loss ◽  
Post Filter

A retarding Wien filter has been installed in the transmission electron microscope (TEM) JEM-1200EX. The filter is immersed in a high potential (-Ht + Uo ) nearly equal to the accelerating potential (-Ht) to get high energy resolution. The Wien filter consists of crossed electric (E) and magnetic (B) fields perpendicular to the optical axis. Electrons with a particular velocity v have a straight optical axis if the balancing condition between electric and magnetic forces (Wien condition: E=vB) is satisfied. Electrons with different velocity are deflected.Fig. 1 shows a schematic outline of the present instrument. It consists of (1) TEM, (2) an analyzer made of the Wien filter, deflectors and post filter lenses, and (3) a TV camera imaging system and serial detection system. The analyzer and a serial detection system are controlled by a personal computer PC-9801VX (PC). Table 1 shows currents and voltages of the filter, lenses and deflectors (upper) and those for TEM (lower).

Energy-Filtered CTEM Image of MgO Smoke Particles

1985 ◽  
Vol 43 ◽  
pp. 410-411
Author(s):  
Y. Kondo ◽  
T. Yoshioka ◽  
T. Oikawa ◽  
Y. Kokubo ◽  
M. Kersker
Keyword(s):  
Electron Microscope ◽  
Energy Resolution ◽  
Transmission Electron Microscope ◽  
High Energy ◽  
Scanning Transmission Electron Microscope ◽  
High Energy Resolution ◽  
Energy Analyzer ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Sector Type

The energy filtered imaging technique has so far been carried out in a scanning transmission electron microscope (STEM) fitted with a sector type energy analyzer. The STEM has a disadvantage of low beam parallelity because it uses a convergent beam, while the conventional transmission electron microscope (CTEM) allows good phase contrast and diffraction contrast to be obtained because of the high parallelity of the beam, and allows also high resolution images to be obtained. The technique to obtain energy filtered CTEM images has thus far been carried out by a Castaing-Henry type filter or an Ω type filter. However, these filters have the disadvantage of lower energy resolution than conventional sector type energy analyzer at the present time. This paper reports energy filtered CTEM images of MgO smoke, obtained using a new scanning CTEM image technique and a high energy resolution sector type energy analyzer which can resolve bulk and surface plasmon energy.

A High Energy-resolution Wavelength-dispersive Soft-X-ray Spectrometer for a Transmission Electron Microscope to Investigate Valence Electrons

2004 ◽  
Vol 10 (S02) ◽  
pp. 1044-1045 ◽  
Author(s):  
Masami Terauchi
Keyword(s):  
Electron Microscope ◽  
Energy Resolution ◽  
Transmission Electron Microscope ◽  
High Energy ◽  
High Energy Resolution ◽  
X Ray ◽  
Transmission Electron ◽  
Valence Electrons

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

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