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Co-Crystals as a Pharmaceutical Strategy for Altering API Physicochemical Properties
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Co-Crystals as a Pharmaceutical Strategy for Altering API Physicochemical Properties

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 6091

Special Issue Editors

Prof. Dr. Maria Cristina Bonferoni

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Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: amphiphilic polymers; bioactive polysaccharides; nanoemulsions; poorly soluble drug formulations; nanoparticles; theranostic
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Laura Catenacci

E-Mail Website
Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: solid-state characterization; thermal analysis; cyclodextrins; drug delivery; poorly soluble drugs formulation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Milena Sorrenti

E-Mail Website
Guest Editor
Department of Drug Sciences, Università degli Studi di Pavia, Pavia, Italy
Interests: solid-state characterization; cyclodextrins; drug delivery; poorly soluble drugs formulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Co-crystals are defined as “a connection of at least two molecules in a solid state within the same crystal lattice”. In pharmaceutical co-crystals, one component is a drug and the other is a neutral molecule of co-former that should be pharmacologically inert, or even all the two components are drugs in the perspective of synergistic activity or multitarget therapy. The co-crystal components are bonded together via noncovalent bonds such as π–π stacking, van der Waals forces, and hydrogen bonding. With respect to salts, co-crystals can therefore also be obtained in the case of non-ionizable compounds. The crystal properties are affected by the composition and the arrangement of molecules in the lattice, so that the choice of the most suitable co-former allows direct control over physicochemical properties, such as, in particular, drug solubility. Co-crystal formation shows advantages in particular for drugs characterized by low bioavailability related to poor solubility in water (Class II and IV of the Biopharmaceutical Classification System). In addition to solubility, other physicochemical properties can be positively affected by co-crystallization, such as melting point, bulk density, compressibility, hygroscopicity, taste masking or mechanical properties, with a relevant impact on dosage form production and stability. Co-crystal formation is gaining increasing attention from a regulatory point of view and offers new opportunities in intellectual properties protection and exploitation.

The aim of the issue encompasses co-crystals design, preparation, and characterization, and their application for the improvement of drug properties and dosage form preparation.

Prof. Dr. Maria Cristina Bonferoni
Prof. Dr. Laura Catenacci
Prof. Dr. Milena Sorrenti
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Co-crystals
  • Co-formers
  • Poorly soluble drugs
  • Solubility enhancement
  • Drug stability
  • Physicochemical characterization
  • Regulatory aspects

Published Papers (2 papers)

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Research

16 pages, 6771 KiB  
Article
Analysis of Co-Crystallization Mechanism of Theophylline and Citric Acid from Raman Investigations in Pseudo Polymorphic Forms Obtained by Different Synthesis Methods
by Yannick Guinet, Laurent Paccou and Alain Hédoux
Molecules 2023, 28(4), 1605; https://doi.org/10.3390/molecules28041605 - 07 Feb 2023
Viewed by 1387
Abstract
Designing co-crystals can be considered as a commonly used strategy to improve the bioavailability of many low molecular weight drug candidates. The present study has revealed the existence of three pseudo polymorphic forms of theophylline–citric acid (TP–CA) co-crystal obtained via different routes of [...] Read more.
Designing co-crystals can be considered as a commonly used strategy to improve the bioavailability of many low molecular weight drug candidates. The present study has revealed the existence of three pseudo polymorphic forms of theophylline–citric acid (TP–CA) co-crystal obtained via different routes of synthesis. These forms are characterized by different degrees of stability in relation with the strength of intermolecular forces responsible for the co-crystalline cohesion. Combining low- and high-frequency Raman investigations made it possible to identify anhydrous and hydrate forms of theophylline–citric acid co-crystals depending on the preparation method. It was shown that the easiest form to synthesize (form 1′), by milling one hydrate with an anhydrous reactant, is very metastable, and transforms into the anhydrous form 1 upon heating or into the hydrated form 2 when it is exposed to humidity. Raman investigations performed in situ during the co-crystallization of forms 1 and 2 have shown that two different types of H-bonding ensure the co-crystalline cohesion depending on the presence of water. In the hydrated form 2, the cohesive forces are related to strong O–H … O H-bonds between water molecules and the reactants. In the anhydrous form 1, the co-crystalline cohesion is ensured by very weak H-bonds between the two anhydrous reactants, interpreted as corresponding to π-H-bonding. The very weak strength of the cohesive forces in form 1 explains the difficulty to directly synthesize the anhydrous co-crystal. Full article
(This article belongs to the Special Issue Co-Crystals as a Pharmaceutical Strategy for Altering API Physicochemical Properties)
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22 pages, 6599 KiB  
Article
Formation of Prenylated Chalcone Xanthohumol Cocrystals: Single Crystal X-ray Diffraction, Vibrational Spectroscopic Study Coupled with Multivariate Analysis
by Iwona Budziak, Marta Arczewska and Daniel M. Kamiński
Molecules 2019, 24(23), 4245; https://doi.org/10.3390/molecules24234245 - 21 Nov 2019
Cited by 16 | Viewed by 3598
Abstract
Four novel xanthohumol (XN) cocrystals with pharmaceutically acceptable coformers, such as nicotinamide (NIC), glutarimide (GA), acetamide (AC), and caffeine (CF) in the 1:1 stoichiometry were obtained by the slow evaporation solution growth technique. The structure of the cocrystals was determined by single crystal [...] Read more.
Four novel xanthohumol (XN) cocrystals with pharmaceutically acceptable coformers, such as nicotinamide (NIC), glutarimide (GA), acetamide (AC), and caffeine (CF) in the 1:1 stoichiometry were obtained by the slow evaporation solution growth technique. The structure of the cocrystals was determined by single crystal X-ray diffraction. The analysis of packing and interactions in the crystal lattice revealed that molecules in the target cocrystals were packed into almost flat layers, formed by the O–H⋅⋅⋅O, O–H⋅⋅⋅N, and N–H⋅⋅⋅O-type contacts between the xanthohumol and coformer molecules. The results provided details about synthons responsible for crystal net stabilization and all hydrogen bonds observed in the crystal lattice. The main synthon was formed via the hydrogen bond between the hydroxyl group in the B ring of XN and coformers. The three-dimensional crystal lattice was stabilized by the hydrogen XN−XN interactions whereas the π–π stacking interactions played an additional role in layer binding, with the exception of low quality cocrystals formed with caffeine. Application of FTIR and Raman spectroscopy confirmed that the crystalline phase of obtained cocrystals was not a simple combination of individual components and completely different crystal phases resulted from the effect of intermolecular interactions. The multivariate analysis showed the changes in the spectra, and this technique can be applied in a combination with vibrational spectroscopy for fast screening of new crystal phases. Additionally, the solubility studies of pure XN and its cocrystals exhibited a 2.6-fold enhancement in XN solubility in aqueous solution for XN–AC and, to a lesser extent, for other cocrystals. Full article
(This article belongs to the Special Issue Co-Crystals as a Pharmaceutical Strategy for Altering API Physicochemical Properties)
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