Pharmaceutical Salts: Comprehensive Insights From Fundamental Chemistry to FDA Approvals (2019–2023)

AAPS PharmSciTech, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 16, 2025

Language: Английский

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Deciphering Imatinib Multicomponent Crystals: Insights from X-Ray Crystallography and Solid-State NMR Spectroscopy

Crystal Growth & Design, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

We focused on the critical role of crystallization active pharmaceutical ingredients (APIs) in drug development, with particular emphasis stability, solubility, and feasibility formulation manufacturing. explored polymorphism APIs formation multicomponent crystals, including salt cocrystal screening, underscoring significance regulatory intellectual property considerations recognizing salts cocrystals solid forms. Our study led to design seven new crystalline forms imatinib, an oncology API. Using X-ray crystallography solid-state NMR, we elucidated hydrogen bonding interactions proton transfer, unveiling along salt–cocrystal continuum. Most demonstrated improved aqueous solubility compared that free base form. This research provides valuable insights into structural details compounds emphasizes importance understanding for rational APIs, thereby enhancing development process.

Language: Английский

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Pharmaceutical Cocrystals for Drug Delivery

Burger's Medicinal Chemistry and Drug Discovery, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 62

Published: May 26, 2025

Abstract Pharmaceutical cocrystals offer the ability to tune solubility, permeability, tableting, and bioavailability of a solid, oral drug formulation without changing chemical structure molecule. Crystal engineering pharmaceutical salts via supramolecular heterosynthons with acceptable generally recognized as safe (GRAS) coformers provides platform technology for improving efficacy optimal delivery. With almost 90% drugs in Biopharmaceutics Classification System (BCS) class II IV suffering from low‐solubility and/or low‐permeability challenges, have provided an opportune intervention populating pipeline over past decade. From prototype cocrystal itraconazole‐succinic acid first salt‐cocrystal complex Entresto containing valsartan‐sacubitril, this review covers origins subject early 2000s peak growth curve model systems between 2005 2015, successful lab‐to‐market translation witnessed The combined application machine learning neural network tools is bringing speed accuracy research exercise designing drug–coformer therapeutic properties. This article snapshot summary latest trends leading discovery, development, continuous manufacturing.

Language: Английский

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The Hydrogen‐Bond Continuum in the Salt/Cocrystal Systems of Quinoline and Chloro‐Nitrobenzoic Acids

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(68)

Published: Aug. 23, 2024

Abstract This study investigates the hydrogen‐bond geometry in six two‐component solid systems composed of quinoline and chloro‐nitrobenzoic acids. New X‐ray diffraction studies were conducted using both conventional independent‐atom model more recent Hirshfeld atom‐refinement method, with latter providing precise hydrogen‐atom positions. The can be divided into salts (the hydrogen atom transferred to nitrogen), cocrystals retained by acid), intermediate structures. Solid‐state NMR experiments corroborated diffraction‐derived H−N distances. DFT calculations, five functionals including hybrid B3LYP PBE0, showed varying energy profiles for bonds, notable differences across functionals. These calculations revealed different preferences salt or cocrystal structures, depending on functional used. Path‐integral molecular dynamics simulations incorporating nuclear quantum effects demonstrated significant delocalization, forming a continuum, provided average N−H distances excellent agreement experimental results. comprehensive theoretical approach highlights complexity multicomponent solids. emphasizes that classification is frequently inadequate, as often significantly delocalized bond. insight crucial understanding predicting behavior such pharmaceutical applications.

Language: Английский

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Charting the salt–cocrystal continuum of acid–base multicomponent crystals with hybrid density functional theory

CrystEngComm, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The protonation state in acid–base multicomponent crystals is challenging to determine. An efficient procedure, leveraging modern implementations of hybrid density functional theory (DFT), shown efficiently identify the nature such crystals.

Language: Английский

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Cocrystals and Salts: The Structural Landscape of Multicomponent Solids of Chalcogenadiazoles

Crystal Growth & Design, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

To explore the structural landscape of a variety 1,3,4-chalcogenadiazoles, more than 150 cocrystallization reactions with carboxylic acids as potential coformers were attempted, and outcome each was characterized classified using FTIR. The results from FTIR screen subsequently confirmed single-crystal X-ray diffraction products (12 found to be salts, remaining 5 cocrystals). It noted that common ΔpKa "rule" did not provide reliable information on salt vs cocrystal formation in these systems, whereas use calculated interaction energies for neutral salt-based heteromeric dimers identified noticeable separation between two, indicating such calculations can offer useful predictor reactions.

Language: Английский

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Thiabendazole: Fumaric acid as a case study on the salt cocrystal continuum: A local vibrational mode perspective

Chemical Physics Letters, Journal Year: 2024, Volume and Issue: unknown, P. 141772 - 141772

Published: Nov. 1, 2024

Language: Английский

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