scholarly journals Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 241
Author(s):  
Vânia André ◽  
M. Teresa Duarte ◽  
Clara S. B. Gomes ◽  
Mafalda C. Sarraguça
Keyword(s):  
Crystal Engineering ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Inorganic Synthesis ◽  
Crystal Forms ◽  
Crystalline Materials ◽  
Pharmaceutical Ingredients ◽  
Research Areas ◽  
Metal Organic ◽  
Synthesized Materials

In Portugal, publications with mechanochemical methods date back to 2009, with the report on mechanochemical strategies for the synthesis of metallopharmaceuticals. Since then, mechanochemical applications have grown in Portugal, spanning several fields, mainly crystal engineering and supramolecular chemistry, catalysis, and organic and inorganic chemistry. The area with the most increased development is the synthesis of multicomponent crystal forms, with several groups synthesizing solvates, salts, and cocrystals in which the main objective was to improve physical properties of the active pharmaceutical ingredients. Recently, non-crystalline materials, such as ionic liquids and amorphous solid dispersions, have also been studied using mechanochemical methods. An area that is in expansion is the use of mechanochemical synthesis of bioinspired metal-organic frameworks with an emphasis in antibiotic coordination frameworks. The use of mechanochemistry for catalysis and organic and inorganic synthesis has also grown due to the synthetic advantages, ease of synthesis, scalability, sustainability, and, in the majority of cases, the superior properties of the synthesized materials. It can be easily concluded that mechanochemistry is expanding in Portugal in diverse research areas.

scholarly journals Trapping liquid drugs inside crystals

2014 ◽  
Vol 70 (a1) ◽  
pp. C984-C984
Author(s):  
Alessia Bacchi ◽  
Davide Capucci ◽  
Paolo Pelagatti
Keyword(s):  
Human Health ◽  
Crystal Engineering ◽  
Room Temperature ◽  
The Body ◽  
New Materials ◽  
Active Molecule ◽  
Crystalline Materials ◽  
Pharmaceutical Ingredients ◽  
Solid Dosage ◽  
Intellectual Properties

The objective of this work is to embed liquid or volatile pharmaceuticals inside crystalline materials, in order to tune their delivery properties in medicine or agrochemistry, and to explore new regulatory and intellectual properties issues. Liquid or volatile formulations of active pharmaceutical ingredients (APIs) are intrinsically less stable and durable than solid forms; in fact most drugs are formulated as solid dosage because they tend to be stable, reproducible, and amenable to purification. Most drugs and agrochemicals are manufactured and distributed as crystalline materials, and their action involves the delivery of the active molecule by a solubilization process either in the body or on the environment. However some important compounds for the human health or for the environment occur as liquids at room temperature. The formation of co-crystals has been demonstrated as a means of tuning solubility properties of solid phases, and therefore it is widely investigated by companies and by solid state scientists especially in the fields of pharmaceuticals, agrochemicals, pigments, dyestuffs, foods, and explosives. In spite of this extremely high interest towards co-crystallization as a tool to alter solubility, practically no emphasis has been paid to using it as a means to stabilize volatile or labile or low-melting products. In this work we trap and stabilize volatile and liquid APIs and agrochemicals in crystalline matrices by engineering suitable co-crystals. These new materials alter the physic state of the active ingredients allowing to expand the phase space accessible to manufacturing and delivery. We have defined a benchmark of molecules relevant to human health and environment that have been combined with suitable partners according to the well known methods of crystal engineering in order to obtain cocrystals. The first successful results will be discussed; the Figure shows a cocrystal of propofol, a worldwide use anesthetic.

Crystal Engineering for Catalysis

2018 ◽  
Vol 9 (1) ◽  
pp. 283-309 ◽  
Author(s):  
Jeffrey D. Rimer ◽  
Aseem Chawla ◽  
Thuy T. Le
Keyword(s):  
Crystal Engineering ◽  
Active Sites ◽  
Heterogeneous Catalysts ◽  
Computational Design ◽  
Crystal Nucleation ◽  
Synthesis Methods ◽  
Crystalline Materials ◽  
Simultaneous Control ◽  
Metal Organic ◽  
Controlled Environments

Crystal engineering relies upon the ability to predictively control intermolecular interactions during the assembly of crystalline materials in a manner that leads to a desired (and predetermined) set of properties. Economics, scalability, and ease of design must be leveraged with techniques that manipulate the thermodynamics and kinetics of crystal nucleation and growth. It is often challenging to exact simultaneous control over multiple physicochemical properties, such as crystal size, habit, chirality, polymorph, and composition. Engineered materials often rely upon postsynthesis (top-down) processes to introduce properties that would otherwise be challenging to attain through direct (bottom-up) approaches. We discuss the application of crystal engineering to heterogeneous catalysts with a focus on four general themes: ( a) tailored nanocrystal size, ( b) controlled environments surrounding active sites, ( c) tuned morphology with well-defined facets, and ( d) hierarchical materials with disparate pore size and active site distributions. We focus on nonporous materials, including metals and metal oxides, and two classes of porous materials: zeolites and metal organic frameworks. We review novel synthesis methods involving synergistic experimental and computational design approaches, the challenges facing catalyst development, and opportunities for future advancement in crystal engineering.

CO-CRYSTALLIZATION: TECHNIQUE FOR IMPROVEMENT OF PHARMACEUTICAL PROPERTIES

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (09) ◽  
pp. 5-11
Author(s):  
S. S Pekamwar ◽  
◽  
D. D. Gadade ◽  
G. K. Kale
Keyword(s):  
Crystal Engineering ◽  
Solid Dispersions ◽  
Physicochemical Characteristics ◽  
Potential Effect ◽  
Drug Formulation ◽  
Intrinsic Activity ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Physical Form ◽  
Pharmaceutical Properties

Physicochemical characteristics of active pharmaceutical compounds, including solubility and flow properties, are crucial in the development of drug formulation. The physical form of compound and formulation has potential effect on biopharmaceutical parameters of the drug. The crystal engineering approach can be employed for modification of physicochemical properties of the active pharmaceutical ingredients whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of co-crystals to modify physicochemical characteristics of active pharmaceutical ingredients along with case studies.

scholarly journals Miscibility and thermal properties of poly(vinylpyrrolidone-vinyl acetate)/lamivudine and tenofovir binary blends prepared by hot melt extrusion

2021 ◽  
Vol 10 (3) ◽  
pp. 109-116
Author(s):  
Marcos L Dias ◽  
Lucyenne S Barbosa ◽  
Rodrigo B Anjos ◽  
Adriana PD Baptista ◽  
Fabio ML Dantas
Keyword(s):  
Vinyl Acetate ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Melt Extrusion ◽  
High Concentration ◽  
Binary Blends ◽  
Pharmaceutical Ingredients ◽  
Immunodeficiency Syndrome ◽  
Hot Melt

Preparation of amorphous solid dispersions (ASD) by hot melt extrusion (HME) of poly(vinylpyrrolidone-vinyl acetate) (Kollidon) and the active pharmaceutical ingredients (API) Lamivudine (3TC) and Tenofovir Disoproxyl Fumarate (TDF) was investigated aiming to study their miscibility and thermal behavior. These two drugs are currently used as drugs in first line treatment of patients with Acquired Immunodeficiency Syndrome (AIDS). In order to predetermine parameters for extrusion and the maximum concentration of API to be used without any recrystallization, binary blends were first processed in the mixing chamber at 130°C using a roller type rotor at 10, 20 and 30 rpm for 7 min, giving rise to ASD of both API, at least up to 20 wt% of the drug. Both 3TC and TDF were then extruded individually with Kollidon in a single screw extruder. HME produced ASD with high concentration of both Kollidon/API combinations, being part of the API soluble in the polymer matrix. From HME, Kollidon/3TC forms ASD in concentration up to 50 wt%, but from 30 wt% 3TC, the ASD has no time stability, showing recrystallization in less than 5 months, while the Kollidon/TDF system forms ASD up to 30 wt% of TDF, but it has aging stability inferior to 4 months.

Nano Cocrystals: Crystal Engineering from a Nanotechnology Perspective

2020 ◽  
Vol 26 ◽  
Author(s):  
Arun Kumar ◽  
Arun Nanda
Keyword(s):  
Crystal Engineering ◽  
Solid Dispersions ◽  
Pharmaceutical Research ◽  
Aqueous Solubility ◽  
Oral Route ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Drug Molecules ◽  
Further Development ◽  
Pharmaceutical Research And Development

: Low aqueous solubility and poor bioavailability are the major hurdles during drug development for the oral route. A large number of the newly discovered drug molecules fall under BCS II class and have solubility related issues and hence poses low oral bioavailability, which in turn render them as non-suitable candidates for further development. A multitude of solubility enhancement approaches are available, notable among them are salt formation, solid dispersions, inclusion complexes, cocrystallization, nanonization etc. Cocrystallization and Nanonization are among the most widely used approaches in the pharmaceutical field that offer multiple enhancements to the active pharmaceutical ingredients. This review endeavours to cover the recent work, important finding, advantages offered by nano sized cocrystals and their future aspects and challenges in the implementation of this newer approach in pharmaceutical research and development.

Pillar-layered MOFs: functionality, interpenetration, flexibility and applications

2018 ◽  
Vol 6 (40) ◽  
pp. 19288-19329 ◽  
Author(s):  
Farnoosh ZareKarizi ◽  
Monika Joharian ◽  
Ali Morsali
Keyword(s):  
Metal Organic Frameworks ◽  
Crystalline Materials ◽  
Research Areas ◽  
Metal Organic

Pillar-layered metal–organic frameworks (MOFs) are among the most interesting research areas in crystalline materials.

scholarly journals Characterization Methods of Amorphous Form Stability in Solid Dispersion : A Review

2020 ◽  
Vol 2 (2) ◽  
pp. 55
Author(s):  
Maria Elvina Tresia Butarbutar ◽  
Nasrul Wathoni ◽  
Yoga Windu Wardhana
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Physicochemical Characterization ◽  
Amorphous Solid ◽  
Stable Form ◽  
Characterization Methods ◽  
Amorphous Form ◽  
Pharmaceutical Ingredients ◽  
The Stability ◽  
Form Stability

Solubility as a cause of ineffective active pharmaceutical ingredients (API) needs to be a concern. One of the solutions to increase the solubility by choosing active ingredients in the amorphous form. However, the amorphous form tends to be unstable because it has high Gibbs free energy and molecular mobility. To overcome those properties solid dispersion methods can be an answer. The dispersion of the amorphous form in the polymer is expected to prevent the transformation of API to crystal stable form. The solid dispersion (SD) resulted needs for physicochemical characterization to prove the ability of SD to maintain the amorphous form. Therefore, the physicochemical properties of the amorphous solid dispersions (ASDs) have to analyze there in any interactions that are able to occur between the drug and the polymer. Also for evaluate the stability of the ASDs within a certain period. In the article presents, some articles related with ASDs and its characterization will studying, include several product on the market as example. The number of literature used in this article is 69 articles.Keywords: Solubility, amorphous for, solid dispersion, characterization ASDs.

Crystal Engineering for Enhanced Solubility and Bioavailability of Poorly Soluble Drugs

2018 ◽  
Vol 24 (21) ◽  
pp. 2473-2496 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Erfaneh Ghassami ◽  
Saeedeh Ahmadipour
Keyword(s):  
Crystal Engineering ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Pharmaceutical Sciences ◽  
Pharmaceutical Ingredients ◽  
Drug Molecules ◽  
Enhanced Solubility ◽  
Wide Range ◽  
Poorly Soluble ◽  
Low Solubility

Background: Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. Methods: This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS). Results: These techniques include; crystalline habit modification, polymorphism, solvates and hydrates, cocrystals, surface modification, crystallization, spherical agglomeration, liquisolid crystals and solid dispersions which are introduced and discussed in this review article. Conclusion: Each of these techniques has advantages and limitations which are emphasized on them.

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