Advances in Pharmaceutical Cocrystal Design and Technological Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 565

Special Issue Editors


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Guest Editor
1. Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre and Medina Allende, Science Building 2, Cordoba X5000HUA, Argentina
2. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, CONICET, Consejo Nacional de Investigaciones Científicas y Técnicas, UNITEFA, Cordoba X5000HUA, Argentina
Interests: supramolecular chemistry; polymorphs; cyclodextrins; pharmaceutical nanotechnology

E-Mail Website
Guest Editor
1. Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre and Medina Allende, Science Building 2, Cordoba X5000HUA, Argentina
2. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, CONICET, Consejo Nacional de Investigaciones Científicas y Técnicas, UNITEFA, Cordoba X5000HUA, Argentina
Interests: antimicrobial drugs; polymorphs; biopharmacy

E-Mail Website
Guest Editor
1. Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre and Medina Allende, Science Building 2, Cordoba X5000HUA, Argentina
2. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, CONICET, Consejo Nacional de Investigaciones Científicas y Técnicas, UNITEFA, Cordoba X5000HUA, Argentina
Interests: pharmaceutics; drug development; drug delivery systems; ligand–receptor interactions; nanoparticles; solid-state characterization; biodegradation; physical and chemical stability
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Special Issue Information

Dear Colleagues,

Pharmaceutical cocrystals have been extensively studied for their ability to enhance the physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs). However, recent advances have led to their integration into innovative drug delivery platforms, expanding their potential applications beyond traditional solid dosage forms. This Special Issue aims to highlight cutting-edge research on the design, formation, and application of pharmaceutical cocrystals in new technological platforms. Topic of interest include, but are not limited to, cocrystal-based formulations in transdermal and microneedle systems, inhalable drug delivery, 3D printing pharmaceuticals, and nanoscale drug carriers. Papers exploring novel characterization techniques, stability enhancement strategies, and regulatory perspectives are also welcome. By encouraging discussions of these advances, this Special Issue aims to bridge the gap between fundamental cocrystal research and its translational impact on modern pharmaceutical technologies.

Dr. María Soledad Bueno
Dr. Marcela Raquel Longhi
Dr. Claudia Garnero
Guest Editors

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Keywords

  • pharmaceutical cocrystal
  • cocrystal design and formation
  • advanced drug delivery systems
  • transdermal and microneedle applications
  • inhalable formulations
  • 3D printing of pharmaceuticals
  • nanotechnology in drug delivery
  • stability and characterization of cocrystals
  • regulatory aspects of cocrystal-based formulation

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Published Papers (1 paper)

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Research

18 pages, 23959 KB  
Article
Cocrystallization of Ezetimibe with Organic Acids: Stoichiometric Optimization for Improved Solubility and Bioavailability
by Ravi Maharjan, Ha Eun Park, Ki Hyun Kim, Mansingh Chaudhary, Ki-Taek Kim, Minji Kim, Hea-Young Cho and Seong Hoon Jeong
Pharmaceutics 2025, 17(11), 1399; https://doi.org/10.3390/pharmaceutics17111399 - 29 Oct 2025
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Abstract
Background/Objectives: Pharmaceutical cocrystallization offers a promising strategy to enhance drug properties while preserving molecular integrity. Ezetimibe, a BCS Class II hypolipidemic agent, faces therapeutic limitations due to poor aqueous solubility. This study aimed to systematically evaluate cocrystallization of ezetimibe with organic acid (benzoic, [...] Read more.
Background/Objectives: Pharmaceutical cocrystallization offers a promising strategy to enhance drug properties while preserving molecular integrity. Ezetimibe, a BCS Class II hypolipidemic agent, faces therapeutic limitations due to poor aqueous solubility. This study aimed to systematically evaluate cocrystallization of ezetimibe with organic acid (benzoic, tartaric, or succinic acid) at varying stoichiometric ratios (1:0.5–1:2) to optimize physicochemical properties and oral bioavailability. Methods: Cocrystals were prepared via solvent evaporation (SEV) and solvent/anti-solvent (SAS) methods. Structural characterization included Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder/single-crystal X-ray diffraction (PXRD/SCXRD). Physicochemical performance was assessed through saturation solubility, in vitro dissolution, and in vivo pharmacokinetics in male Sprague Dawley rats (n = 4/group). Results: Benzoic acid cocrystals (1:2 ratio, SEV) showed O−H⋯N hydrogen bonding (FTIR band shifts: 2928 → 3264 cm−1) and novel crystalline phases (12.4°, 16.7°, and 24.9°). SCXRD confirmed monoclinic P21/n symmetry (a = 5.42 Å, b = 5.05 Å) for benzoic acid cocrystals. Ezetimibe/benzoic acid cocrystals (1:2) achieved 64-fold solubility enhancement and 2× faster dissolution vs. pure ezetimibe. Pharmacokinetics revealed 3× higher Cmax (18.38 ng/mL) and 4× greater AUC (40.36 h·ng/mL) for optimized cocrystals. Tartaric and succinic acid cocrystals showed moderate improvements, with melting points intermediate between parent compounds. Conclusions: Both stoichiometry and preparation method strongly determined cocrystal performance. Benzoic acid at a 1:2 ratio via SEV demonstrated superior solubility, dissolution, and bioavailability, addressing ezetimibe’s formulation challenges. These findings underscore the potential of rational cocrystal design to overcome solubility barriers in oral dosage development, particularly for hydrophobic therapeutics. Full article
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