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Journal articles on the topic 'Drug-Drug Cocrystal'

Author: Grafiati

Published: 2 June 2025

Last updated: 31 July 2025

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1

Ul Islam, Noor, Ezzat Khan, Muhammad Naveed Umar, et al. "Enhancing Dissolution Rate and Antibacterial Efficiency of Azithromycin through Drug-Drug Cocrystals with Paracetamol." Antibiotics 10, no. 8 (2021): 939. http://dx.doi.org/10.3390/antibiotics10080939.

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Cocrystallization is a promising approach to alter physicochemical properties of active pharmaceutical ingredients (hereafter abbreviated as APIs) bearing poor profile. Nowadays pharmaceutical industries are focused on preparing drug-drug cocrystals of APIs that are often prescribed in combination therapies by physicians. Physicians normally prescribe antibiotic with an analgesic/antipyretic drug to combat several ailments in a better and more efficient way. In this work, azithromycin (AZT) and paracetamol (PCM) cocrystals were prepared in 1:1 molar ratio using slow solvent evaporation method.

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2

Tamang, Rejoys, Ammon Tamang, and Sayani Bhattacharyya. "Formulation and evaluation of orodispersible tablet of dolutegravir -methionine cocrystal." Fabad Journal of Pharmaceutical Sciences 50, no. 1 (2025): 1–14. https://doi.org/10.55262/fabadeczacilik.1516443.

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Dolutegravir, a newly approved anti-HIV medication is insoluble in the normal gastric pH range and that results in slow onset of action. The research proposes cocrystallization process to increase the solubility of the drug and hence dissolution. The cocrystals of dolutegravir were formulated using methionine as coformers by solvent evaporation method. The cocrystals were evaluated for solubility, in vitro drug release, and solid-state characterization, study. The orodispersible tablets of dolutegravir cocrystal were successfully prepared by direct compression method. The solid-state character

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3

Bhalekar, Mangesh, and Sumedh Bandu Pradhan. "Scientific Coformer Screening, Preparation and Evaluation of Fenofibrate Tartaric Acid Cocrystal." Journal of Drug Delivery and Therapeutics 9, no. 4 (2019): 406–10. http://dx.doi.org/10.22270/jddt.v9i4.3199.

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Objective: This present study aims to screen pharmaceutical cocrystal of Fenofibrate and coformers. Further the preparation and evaluation of fenofibrate-coformer cocrystal and In-Vitro drug release and Ex-Vivo Permeation study was done. Material and Methods: The coformers for Fenofibrate were screened using molecular docking. The cocrystals produced were characterized using Differential Scanning Calorimetry (DSC), X-ray diffraction (XRPD) study and Infrared spectroscopy. Results: Cocrystal of Fenofibrate with tartaric acid was successfully prepared. The cocrystals displayed enhanced dissoluti

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4

P. Ahirrao, Sapana, Mayur P. Sonawane, Deepak S. Bhambere, et al. "Cocrystal Formulation: A Novel Approach to Enhance Solubility and Dissolution of Etodolac." Biosciences Biotechnology Research Asia 19, no. 1 (2022): 111–19. http://dx.doi.org/10.13005/bbra/2971.

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Etodolac (ETD) is a non-steroidal anti-inflammatory drug (NSAID) given in rheumatoid arthritis treatment. As it comes under BCS class II drug hence it exhibits low water solubility. Also, its dissolution rate-limited oral absorption results in delayed onset of action. The Novel approach in the solubility enhancement field; crystal engineering was preferred to prepare pharmaceutical cocrystals of etodolac with GRAS (generally recognized as safe) molecules. Pharmaceutical cocrystals of etodolac were prepared with p-hydroxybenzoic acid and glutaric acid with the drug: coformer ratio 1:1 and 1:2.

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5

Gohel, Sunil Kumar, Vasanthi Palanisamy, Palash Sanphui, Muthuramalingam Prakash, Girij Pal Singh, and Vladimir Chernyshev. "Isostructural cocrystals of metaxalone with improved dissolution characteristics." RSC Advances 11, no. 49 (2021): 30689–700. http://dx.doi.org/10.1039/d1ra05959a.

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Metaxalone forms isostructural cocrystals with nicotinamide and salicylamide that offer a solubility advantage compared to the native drug. A drug–drug homosynthon is retained in all the cocrystal structures.

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6

Kara, Divya Dhatri, and Mahalaxmi Rathnanand. "Cocrystals and Drug–Drug Cocrystals of Anticancer Drugs: A Perception towards Screening Techniques, Preparation, and Enhancement of Drug Properties." Crystals 12, no. 10 (2022): 1337. http://dx.doi.org/10.3390/cryst12101337.

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The most favored approach for drug administration is the oral route. Several anticancer drugs come under this category and mostly lack solubility and oral bioavailability, which are the most common causes of inadequate clinical efficiency. Enhancing oral absorption of anticancer drugs with low aqueous solubility and drug impermeability is currently an effective area of research. Many scientists have looked into pharmaceutical cocrystals as a way to improve the physicochemical properties of several anticancer drugs. Benefits of pharmaceutical cocrystals over other solid forms may include improv

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7

Ullah, Majeed, Hanif Ullah, Ghulam Murtaza, Qaisar Mahmood, and Izhar Hussain. "Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets." BioMed Research International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/870656.

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The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from H

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8

Dhibar, Manami, Santanu Chakraborty, Souvik Basak, et al. "Critical Analysis and Optimization of Stoichiometric Ratio of Drug-Coformer on Cocrystal Design: Molecular Docking, In Vitro and In Vivo Assessment." Pharmaceuticals 16, no. 2 (2023): 284. http://dx.doi.org/10.3390/ph16020284.

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In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.e., cocrystal, was fabricated using different m

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9

Machado Cruz, Ricardo, Tereza Boleslavská, Josef Beránek, et al. "Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal." Pharmaceutics 12, no. 8 (2020): 741. http://dx.doi.org/10.3390/pharmaceutics12080741.

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The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution

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10

Machado, Cruz Ricardo, Tereza Boleslavská, Josef Beránek, et al. "Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal." Pharmaceutics 12 (August 6, 2020): 741. https://doi.org/10.3390/pharmaceutics12080741.

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Abstract: The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and d

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11

Panzade, Prabhakar, Priyanka Somani, and Pavan Rathi. "Nevirapine Pharmaceutical Cocrystal: Design, Development and Formulation." Drug Delivery Letters 9, no. 3 (2019): 240–47. http://dx.doi.org/10.2174/2210303109666190411125857.

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Background and Objective: The top approach to deliver poorly soluble drugs is the use of a highly soluble form. The present study was conducted to enhance the solubility and dissolution of a poorly aqueous soluble drug nevirapine via a pharmaceutical cocrystal. Another objective of the study was to check the potential of the nevirapine cocrystal in the dosage form. Methods: A neat and liquid assisted grinding method was employed to prepare nevirapine cocrystals in a 1:1 and 1:2 stoichiometric ratio of drug:coformer by screening various coformers. The prepared cocrystals were preliminary invest

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12

Lemli, Beáta, Szilárd Pál, Ala’ Salem, and Aleksandar Széchenyi. "Prioritizing Computational Cocrystal Prediction Methods for Experimental Researchers: A Review to Find Efficient, Cost-Effective, and User-Friendly Approaches." International Journal of Molecular Sciences 25, no. 22 (2024): 12045. http://dx.doi.org/10.3390/ijms252212045.

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Pharmaceutical cocrystals offer a versatile approach to enhancing the properties of drug compounds, making them an important tool in drug formulation and development by improving the therapeutic performance and patient experience of pharmaceutical products. The prediction of cocrystals involves using computational and theoretical methods to identify potential cocrystal formers and understand the interactions between the active pharmaceutical ingredient and coformers. This process aims to predict whether two or more molecules can form a stable cocrystal structure before performing experimental

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13

Buddhadev, Sheetal S., and Kevin C. Garala. "Pharmaceutical Cocrystals—A Review." Proceedings 62, no. 1 (2021): 14. http://dx.doi.org/10.3390/proceedings2020062014.

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The design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offers a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of cocrystals, cocrystal preparation and characterization, a comparison of different

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14

Rajesh Goud, N., Ronaq Ali Khan, and Ashwini Nangia. "Modulating the solubility of sulfacetamide by means of cocrystals." CrystEngComm 16, no. 26 (2014): 5859–69. http://dx.doi.org/10.1039/c4ce00103f.

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The antibacterial drug sulfacetamide was screened with pharmaceutically acceptable coformers to discover solid forms with low solubility. Cocrystals with INIC and CAF exhibited 0.64 and 0.68 times the IDR of the parent drug. SACT–CAF cocrystal with lower solubility and good stability is a potential candidate to increase the drug residence time at the site of action for improved therapeutic efficacy.

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15

Emami, Shahram, Mohammadreza Siahi-Shadbad, Khosro Adibkia, and Mohammad Barzegar-Jalali. "Recent advances in improving oral drug bioavailability by cocrystals." BioImpacts 8, no. 4 (2018): 305–20. http://dx.doi.org/10.15171/bi.2018.33.

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Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas incl

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16

Srivastava, Dipti, Zeeshan Fatima, Chanchal D. Kaur, Sachin L. Tulsankar, Sanap S. Nashik, and Dilshad A. Rizvi. "Pharmaceutical Cocrystal: A Novel Approach to Tailor the Biopharmaceutical Properties of a Poorly Water Soluble Drug." Recent Patents on Drug Delivery & Formulation 13, no. 1 (2019): 62–69. http://dx.doi.org/10.2174/1872211313666190306160116.

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Background: The present study reports the formation of a cocrystal of candesartan with the coformer methyl paraben, its characterization and determination of its bioavailability. Candesartan is a poorly water-soluble drug having an anti-hypertensive activity. The recent patents on the cocrystals of the drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib (WO2015170345A1), and Valsartan (CN102702118B) for enhancement of solubility, helped in selection of the drug for this work. Methods: Candesartan cocrystal was prepared by solution crystallization method. The formation of a ne

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17

Kimoto, Kouya, Mitsuo Yamamoto, Masatoshi Karashima, et al. "Pharmaceutical Cocrystal Development of TAK-020 with Enhanced Oral Absorption." Crystals 10, no. 3 (2020): 211. http://dx.doi.org/10.3390/cryst10030211.

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The objective of this study was to improve the solubility of poorly water-soluble drugs by pharmaceutical cocrystal engineering techniques and select the best pharmaceutical forms with high solubility and solubilized formulations for progress from the early discovery stage toward the clinical stage. Several pharmaceutical cocrystals of TAK-020, a Bruton tyrosine kinase inhibitor, were newly discovered in the screening based on the solid grinding method and the slurry method, considering thermodynamic factors that dominate cocrystal formation. TAK-020/gentisic acid cocrystal (TAK-020/GA CC) was

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18

Kalyani, Avhale* Dr. Kawade Rajendra M. Mayuri Lodha Shivani Matsagar Arti Tupe. "Solubility Modification of Phytochemicals via Pharmaceutical Cocrystal." International Journal of Pharmaceutical Sciences 2, no. 12 (2024): 587–97. https://doi.org/10.5281/zenodo.14278837.

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Pharmaceutical cocrystal is an approach to physicochemical and mechanical properties of a drug substance the cocrystal are composed of conformer and API which are mainly used for solubility and dissolution mechanical properties and stability of drug. this review will provide information about what is cocrystal, how they are prepared, what is the advantages behind the pharmaceutical cocrystal preparation, the whole cocrystal development pathway in which all the steps involved in the cocrystal formation from selection of API to the after preparation scale up process are given. the concept of mul

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19

Rathi, Ritu, Yukta Guggal, Twinkle ., Varneet Sandhu, and Inderbir Singh. "Exploring the Patent Landscape and Regulatory Prospective on Pharmaceutical Cocrystals." Journal of Pharmaceutical Technology, Research and Management 11, no. 1 (2023): 49–60. http://dx.doi.org/10.15415/jprtm.2023.111005.

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Background: Cocrystals are not new, they have sparked considerable interest among scientists and the pharmaceutical business in the last decade. Cocrystals are multiphase formations composed of at least two particles that are held together by noncovalent bonds. Cocrystal offers unmatched physio-engineered attributes (like stability, melting point, taste concealment, dissolvability, purity, bioavailability, etc.) without changing the pharmacological capabilities of the drug. Recently, as pharmaceutical cocrystal development has increased, we have given more attention to the absurd state of cocr

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Rathi, Ritu, Yukta Guggal, Twinkle ., Varneet Sandhu, and Inderbir Singh. "Exploring the Patent Landscape and Regulatory Prospective on Pharmaceutical Cocrystals." Journal of Pharmaceutical Technology, Research and Management 11, no. 1 (2023): 49–60. https://doi.org/10.15415/jptrm.2023.111005.

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Background: Cocrystals are not new, they have sparked considerable interest among scientists and the pharmaceutical business in the last decade. Cocrystals are multiphase formations composed of at least two particles that are held together by noncovalent bonds. Cocrystal offers unmatched physio-engineered attributes (like stability, melting point, taste concealment, dissolvability, purity, bioavailability, etc.) without changing the pharmacological capabilities of the drug. Recently, as pharmaceutical cocrystal development has increased, we have given more attention to the absurd state of cocr

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21

Wallace, Catherine S., Margaret P. Davis, and Timothy M. Korter. "Low-Frequency Raman Spectroscopy of Pure and Cocrystallized Mycophenolic Acid." Pharmaceutics 15, no. 7 (2023): 1924. http://dx.doi.org/10.3390/pharmaceutics15071924.

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The aqueous solubility of solid-state pharmaceuticals can often be enhanced by cocrystallization with a coformer to create a binary cocrystal with preferred physical properties. Greater understanding of the internal and external forces that dictate molecular structure and intermolecular packing arrangements enables more efficient design of new cocrystals. Low-frequency (sub-200 cm−1) Raman spectroscopy experiments and solid-state density functional theory simulations have been utilized together to investigate the crystal lattice vibrations of mycophenolic acid, an immunosuppressive drug, in it

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22

Savale, Aishwarya, Rajendra Mogal, Swati Talele, Sumit Deore, and Laxmikant Borse. "Pharmaceutical Cocrystals: A Novel Systematic Approach for the Administration of Existing Drugs in New Crystalline Form." Biosciences Biotechnology Research Asia 20, no. 4 (2023): 1195–210. http://dx.doi.org/10.13005/bbra/3168.

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ABSTRACT: Poor physicochemical properties like solubility, dissolution profile, stability, etc. of drugs remain as an obstacle to formulation development. In the last two decades, pharmaceutical cocrystal gaining lots of interest from researchers as these physicochemical, mechanical, and pharmacokinetic properties can be altered without compromising the therapeutic effect. The multi-component systems wherein one component is essentially the Active Pharmaceutical Ingredient and another may be either one more drug or coformer are termed as pharmaceutical cocrystal. Cocrystal is a novel, promisin

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Gao, Lei, and Xianrui Zhang. "Cocrystallization of Febuxostat with Pyridine Coformers: Crystal Structural and Physicochemical Properties Analysis." Journal of Chemistry 2021 (December 16, 2021): 1–8. http://dx.doi.org/10.1155/2021/3834368.

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Drug cocrystals and salts have promising applications for modulating the physicochemical properties and solubility of pharmaceuticals. In this study, a cocrystal and two salts of febuxostat (FEB) with pyridine nitrogen coformers, including 4, 4′-bipyridine (BIP), 3-aminopyridine (3AP) and 4-hydroxypyridine (4HP), were designed to improve the solubility of FEB. The single-crystal structures were elucidated, and their physical and chemical properties were investigated by IR, PXRD, and DSC. In addition, drug-related properties, including the solubility and powder dissolution rate were assessed. T

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Kara, Aytug, Dinesh Kumar, Anne Marie Healy, Aikaterini Lalatsa, and Dolores R. Serrano. "Continuous Manufacturing of Cocrystals Using 3D-Printed Microfluidic Chips Coupled with Spray Coating." Pharmaceuticals 16, no. 8 (2023): 1064. http://dx.doi.org/10.3390/ph16081064.

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Using cocrystals has emerged as a promising strategy to improve the physicochemical properties of active pharmaceutical ingredients (APIs) by forming a new crystalline phase from two or more components. Particle size and morphology control are key quality attributes for cocrystal medicinal products. The needle-shaped morphology is often considered high-risk and complex in the manufacture of solid dosage forms. Cocrystal particle engineering requires advanced methodologies to ensure high-purity cocrystals with improved solubility and bioavailability and with optimal crystal habit for industrial

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Avdeef, Alex. "Cocrystal solubility-pH and drug solubilization capacity of sodium dodecyl sulfate – mass action model for data analysis and simulation to improve design of experiments." ADMET and DMPK 6, no. 2 (2018): 105–39. http://dx.doi.org/10.5599/admet.505.

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This review discusses the disposition of the anionic surfactant, sodium dodecyl sulfate (SDS; i.e., sodium lauryl sulfate), to solubilize sparingly-soluble drugs above the surfactant critical micelle concentration (CMC), as quantitated by the solubilization capacity (k). A compilation of 101 published SDS k values of mostly poorly-soluble drug molecules was used to develop a prediction model as a function of the drug’s intrinsic solubility, S0, and its calculated H-bond acceptor/donor potential. In almost all cases, the surfactant was found to solubilize the neutral form of the drug. Using the

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Pekamwar, Sanjay S., and Deepak A. Kulkarni. "DEVELOPMENT AND EVALUATION OF BICOMPONENT COCRYSTALS OF ACECLOFENAC FOR EFFICIENT DRUG DELIVERY WITH ENHANCED SOLUBILITY AND IMPROVED DISSOLUTION." INDIAN DRUGS 58, no. 08 (2021): 54–60. http://dx.doi.org/10.53879/id.58.08.12691.

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This research work was intended to improve the solubility and dissolution of aceclofenac by the development of bicomponent cocrystals. Bicomponent cocrystals of aceclofenac were prepared with ten different cocrystal formers (CCF) by neat grinding techniques. Solubility analysis of cocrystals showed that aceclofenac-salicylic acid cocrystals have comparatively better solubility than the other cocrystals. The solubility of pure aceclofenac (309.23 µg/mL) was found to be improved by seven folds (2424.61 µg/mL) due to the formation of bicomponent crystalline form with salicylic acid. In vitro diss

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Nisar, Madiha, Lawrence W. Y. Wong, Herman H. Y. Sung, Richard K. Haynes, and Ian D. Williams. "Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry." Acta Crystallographica Section C Structural Chemistry 74, no. 6 (2018): 742–51. http://dx.doi.org/10.1107/s2053229618006320.

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The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C15H23NO4·C9H8O2). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C15H23NO4·C4H4O4), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza2

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Sokal, Agnieszka, and Edyta Pindelska. "Pharmaceutical Cocrystals as an Opportunity to Modify Drug Properties: From the Idea to Application: A Review." Current Pharmaceutical Design 24, no. 13 (2018): 1357–65. http://dx.doi.org/10.2174/1381612824666171226130828.

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The properties of many drugs which have been available on the pharmaceutical market for a long time still need to be improved. Cocrystals are the solid state drug modification which can improve properties such as low solubility, stability and mechanical properties (e.g. compressibility). In this paper, examples of how to use cocrystals to modify properties of API (Active Pharmaceutical Ingredient) will be reported. Additionally, in this review, the way from an idea of the new cocrystal to drug dosage form registration will be shortly described.

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Kim, Hakyeong, Soeun Jang, and Il Won Kim. "Enhanced Dissolution of Naproxen by Combining Cocrystallization and Eutectic Formation." Pharmaceutics 13, no. 5 (2021): 618. http://dx.doi.org/10.3390/pharmaceutics13050618.

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Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs. Cocrystal formation is one of the methods to alter the physicochemical properties of APIs, but its dissolution behavior in biorelevant media has been scrutinized only in recent years. We investigated the combined strategy of cocrystallization and eutectic formation in this regard and utilized the cocrystal model system of naproxen and three pyridinecarboxamide isomers. Binary melting diagrams were constructed to discover t

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Sanphui, Palash, Geetha Bolla, Ashwini Nangia, and Vladimir Chernyshev. "Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt." IUCrJ 1, no. 2 (2014): 136–50. http://dx.doi.org/10.1107/s2052252514004229.

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Acemetacin (ACM) is a non-steroidal anti-inflammatory drug (NSAID), which causes reduced gastric damage compared with indomethacin. However, acemetacin has a tendency to form a less soluble hydrate in the aqueous medium. We noted difficulties in the preparation of cocrystals and salts of acemetacin by mechanochemical methods, because this drug tends to form a hydrate during any kind of solution-based processing. With the objective to discover a solid form of acemetacin that is stable in the aqueous medium, binary adducts were prepared by the melt method to avoid hydration. The coformers/salt f

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Wang, Na, Chuang Xie, Haijiao Lu, et al. "Cocrystal and its Application in the Field of Active Pharmaceutical Ingredients and Food Ingredients." Current Pharmaceutical Design 24, no. 21 (2018): 2339–48. http://dx.doi.org/10.2174/1381612824666180522102732.

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Background: The development of solid drug dosage form and food ingredients is constrained by their low solubility, low dissolution, low bioavailability and poor physicochemical properties. Formation of cocrystal is a novel and promising method to enhance and improve the properties of materials without breaking the covalent bonds. Methods: The goal of this review is to summarize the cocrystals and their applications in the field of Active Pharmaceutical Ingredients (APIs) and food ingredients (AFIs), mainly on the effective improvements of APIs’ and AFIs’ pharmacokinetic, physicochemical and me

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Pindelska, Edyta, Anita Sarna, Maciej Duszczyk, Anna Zep, and Izabela D. Madura. "Enhancing Febuxostat Solubility Through Cocrystal Formation: Role of Substrate Selection and Amide Coformers." International Journal of Molecular Sciences 26, no. 7 (2025): 3004. https://doi.org/10.3390/ijms26073004.

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Solubility plays a crucial role in drug bioavailability and therapeutic efficacy. Febuxostat (FEB), a BCS Class II drug used to treat hyperuricemia and gout, has low solubility, limiting its effectiveness. Cocrystallization offers a strategy to enhance solubility without modifying the drug’s chemical structure. While FEB exhibits multiple polymorphic forms, no prior studies have explored cocrystal formation from its commercially available hemihydrate. This study examines whether FEB’s initial form—hemihydrate or anhydrous—affects cocrystal formation. We investigated cocrystals with aromatic am

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Wong, Si Nga, Jingwen Weng, Ignatius Ip, et al. "Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline." Pharmaceutics 14, no. 2 (2022): 300. http://dx.doi.org/10.3390/pharmaceutics14020300.

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Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy fo

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Surov, Artem O., Ksenia V. Drozd, Anna G. Ramazanova, et al. "Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance." Pharmaceutics 15, no. 6 (2023): 1747. http://dx.doi.org/10.3390/pharmaceutics15061747.

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Polymorphism is a common phenomenon among single- and multicomponent molecular crystals that has a significant impact on the contemporary drug development process. A new polymorphic form of the drug carbamazepine (CBZ) cocrystal with methylparaben (MePRB) in a 1:1 molar ratio as well as the drug’s channel-like cocrystal containing highly disordered coformer molecules have been obtained and characterized in this work using various analytical methods, including thermal analysis, Raman spectroscopy, and single-crystal and high-resolution synchrotron powder X-ray diffraction. Structural analysis o

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Erxleben, Andrea. "Cocrystal Applications in Drug Delivery." Pharmaceutics 12, no. 9 (2020): 834. http://dx.doi.org/10.3390/pharmaceutics12090834.

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Tao, Yue, Yuhan Gao, Baoxi Zhang, et al. "Advances in Quantitative Analytical Methods for Solid Drugs." Crystals 15, no. 1 (2024): 38. https://doi.org/10.3390/cryst15010038.

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The solid form of the drug can directly affect the physicochemical properties, bioavailability, safety, and efficacy of the drug, and its types mainly include amorphous state, single-component polycrystalline, hydrate, solvate, salt, and cocrystal. Polymorphic drugs are solid drugs whose active ingredients exist in a specific crystalline state. Polymorphic drugs are solid drugs whose active ingredients exist in a specific crystalline state. Drug polymorphism refers to the presence of two or more different crystalline states of the drug. Pharmaceutical cocrystal is a new type of solid form that

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Tutughamiarso, Maya, Guido Wagner, and Ernst Egert. "Cocrystals of 5-fluorocytosine. I. Coformers with fixed hydrogen-bonding sites." Acta Crystallographica Section B Structural Science 68, no. 4 (2012): 431–43. http://dx.doi.org/10.1107/s010876811202561x.

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The antifungal drug 5-fluorocytosine (4-amino-5-fluoro-1,2-dihydropyrimidin-2-one) was cocrystallized with five complementary compounds in order to better understand its drug–receptor interaction. The first two compounds, 2-aminopyrimidine (2-amino-1,3-diazine) and N-acetylcreatinine (N-acetyl-2-amino-1-methyl-5H-imidazol-4-one), exhibit donor–acceptor sites for R 2 2(8) heterodimer formation with 5-fluorocytosine. Such a heterodimer is observed in the cocrystal with 2-aminopyrimidine (I); in contrast, 5-fluorocytosine and N-acetylcreatinine [which forms homodimers in its crystal structure (II

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Vasoya, Jaydip M., Ankita V. Shah, and Abu T. M. Serajuddin. "Investigation of possible solubility and dissolution advantages of cocrystals, I: Aqueous solubility and dissolution rates of ketoconazole and its cocrystals as functions of pH." ADMET and DMPK 7, no. 2 (2019): 106–30. http://dx.doi.org/10.5599/admet.661.

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Since there are conflicting reports in the literature on solubility and dissolution advantages of cocrystals over free forms, we systematically studied solubility and intrinsic dissolution rates of a weakly basic drug, ketoconazole, and its cocrystals with fumaric acid and succinic acid as functions of pH to determine what advantages cocrystals provide. pH-solubility profiles were determined in two different ways: one by lowering pH of ketoconazole aqueous suspensions using HCl, fumaric acid and succinic acid, and the other by adjusting pH of cocrystal suspensions using respective coformer aci

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Rodríguez-Ruiz, Christian, Pedro Montes-Tolentino, Jorge Guillermo Domínguez-Chávez, Hugo Morales-Rojas, Herbert Höpfl, and Dea Herrera-Ruiz. "Tailoring Chlorthalidone Aqueous Solubility by Cocrystallization: Stability and Dissolution Behavior of a Novel Chlorthalidone-Caffeine Cocrystal." Pharmaceutics 14, no. 2 (2022): 334. http://dx.doi.org/10.3390/pharmaceutics14020334.

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A cocrystal of the antihypertensive drug chlorthalidone (CTD) with caffeine (CAF) was obtained (CTD-CAF) by the slurry method, for which a 2:1 stoichiometric ratio was found by powder and single-crystal X-ray diffraction analysis. Cocrystal CTD-CAF showed a supramolecular organization in which CAF molecules are embedded in channels of a 3D network of CTD molecules. The advantage of the cocrystal in comparison to CTD is reflected in a threefold solubility increase and in the dose/solubility ratios, which diminished from near-unit values for D0D to 0.29 for D0CC. Furthermore, dissolution experim

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Guan, Danyingzi, Bianfei Xuan, Chengguang Wang, et al. "Improving the Physicochemical and Biopharmaceutical Properties of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicine through Cocrystal Engineering." Pharmaceutics 13, no. 12 (2021): 2160. http://dx.doi.org/10.3390/pharmaceutics13122160.

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Active pharmaceutical ingredients (APIs) extracted and isolated from traditional Chinese medicines (TCMs) are of interest for drug development due to their wide range of biological activities. However, the overwhelming majority of APIs in TCMs (T-APIs), including flavonoids, terpenoids, alkaloids and phenolic acids, are limited by their poor physicochemical and biopharmaceutical properties, such as solubility, dissolution performance, stability and tabletability for drug development. Cocrystallization of these T-APIs with coformers offers unique advantages to modulate physicochemical propertie

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Choquesillo-Lazarte, Duane, Cristóbal Verdugo-Escamilla, and Juan Manuel García-Ruiz. "Novel solid forms of the analgesic drug ethenzamide." Acta Crystallographica Section A Foundations and Advances 70, a1 (2014): C995. http://dx.doi.org/10.1107/s2053273314090044.

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The interest in multicomponent solid forms has increased in the last years within the pharmaceutical industry and also the solid-state community due to the possibility of obtaining materials with new properties [1]. Crystallization strategies, supported by solvent- and solid-based techniques, have also received attention in the search and development of methodologies for the screening of multicomponent crystals. In this work, ethenzamide, an anti-inflammatory and analgesic drug, was selected as a model drug to develop cocrystals on the basis of the synthon types using a series of phenolic cofo

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Garrido, Camila Caro, Marie Vandooren, Koen Robeyns, Damien P. Debecker, Patricia Luis, and Tom Leyssens. "Combining a Drug and a Nutraceutical: A New Cocrystal of Praziquantel and Curcumin." Crystals 14, no. 2 (2024): 181. http://dx.doi.org/10.3390/cryst14020181.

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This study explores the co-crystallization between the drug praziquantel (PZQ) and the nutraceutical curcumin (CU). The investigation revealed two novel solid forms: a cocrystal solvate with ethyl acetate and a non-solvated cocrystal. This novel drug–nutraceutical cocrystal is a praziquantel–curcumin (2:1) cocrystal. The cocrystal solvate has ethyl acetate molecules occupying the voids with minimal interactions within the crystal lattice. The application of heat treatment induces solvent removal and prompts the transition to the non-solvated cocrystal, as highlighted by variable-temperature X-

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Lv, Wen-Ting, Xiao-Xu Liu, Xia-Lin Dai, Xiang-Tian Long, and Jia-Mei Chen. "A 5-fluorouracil–kaempferol drug–drug cocrystal: a ternary phase diagram, characterization and property evaluation." CrystEngComm 22, no. 46 (2020): 8127–35. http://dx.doi.org/10.1039/d0ce01289k.

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Rodrigues, Marisa, João Lopes, and Mafalda Sarraguça. "Vibrational Spectroscopy for Cocrystals Screening. A Comparative Study." Molecules 23, no. 12 (2018): 3263. http://dx.doi.org/10.3390/molecules23123263.

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A recurrent problem faced by the pharmaceutical industry when formulating drug products concerns poorly soluble drugs, which, despite having desirable pharmacological activity, present limited bioavailability. Cocrystallization is growing up as a possible approach to tackle this problem. Cocrystals are crystalline materials comprising at least two components, solid at room temperature, and held together by non-covalent bonds. The increasing interest in these compounds is steadily demanding faster, simpler, and more reliable methods for the task of screening new cocrystals. This work aims at co

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Li, Duanxiu, Jiong Li, Zongwu Deng, and Hailu Zhang. "Piroxicam–clonixin drug–drug cocrystal solvates with enhanced hydration stability." CrystEngComm 21, no. 28 (2019): 4145–49. http://dx.doi.org/10.1039/c9ce00666d.

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Urano, Maho, Megumi Kitahara, Kae Kishi, et al. "Physical Characteristics of Cilostazol–Hydroxybenzoic Acid Cocrystals Prepared Using a Spray Drying Method." Crystals 10, no. 4 (2020): 313. http://dx.doi.org/10.3390/cryst10040313.

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The cocrystal formation of pharmaceuticals can improve the various physical properties of drugs, such as solubility, without the need for chemical modification of the drug substances. In the present study, we prepared cocrystals of cilostazol and additive coformers (derivatives of hydroxybenzoic acid) using a spray drying method. Based on the preparation of the cocrystals of cilostazol and the coformers as reported previously, the characteristics of the cilostazol cocrystals prepared using solvent evaporation, slurry, and spray drying methods were compared. The physical characterization reveal

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Bolla, Geetha, Sudhir Mittapalli, and Ashwini Nangia. "Celecoxib cocrystal polymorphs†." Acta Crystallographica Section A Foundations and Advances 70, a1 (2014): C1566. http://dx.doi.org/10.1107/s2053273314084332.

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Celecoxib (CEL) is a well-known nonsteroidal anti-inflammatory drug (NSAID) and selectively used from the cocxib family. It is a specific COX-2 inhibitor for pain and inflammation without inhibiting COX-1. A major downside of this popular NSAID is its poor aqueous solubility (9 mg L–1), which limits bioavailability (40%). Several methods were attempted in recent past to overcome solubility issues of the drug. A metastable form-IV showed four times greater solubility and improved bioavailability compared to commercial CEL form-III. Cocrystal of CEL with nicotinamide (CEL–NIC) is reported, but i

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Lee, Min-Jeong, Srinivasulu Aitipamula, Guang J. Choi, and Pui Shan Chow. "Agomelatine–hydroquinone (1:1) cocrystal: novel polymorphs and their thermodynamic relationship." Acta Crystallographica Section B Structural Science, Crystal Engineering and Materials 75, no. 6 (2019): 969–77. http://dx.doi.org/10.1107/s2052520619011739.

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Polymorphism of active pharmaceutical ingredients (APIs) is of significance in the pharmaceutical industry because it can affect the quality, efficacy and safety of the final drug product. In this regard, polymorphic behavior of cocrystals is no exception because it can influence the development of cocrystals as potential drug formulations. The current contribution aims to introduce two novel polymorphs [forms (III) and (IV)] of agomelatine–hydroquinone (AGO-HYQ) cocrystal and to describe the thermodynamic relationship between the cocrystal polymorphs. All polymorphs were characterized using p

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Drozd, Ksenia V., Alex N. Manin, Andrei V. Churakov, and German L. Perlovich. "Novel drug–drug cocrystals of carbamazepine with para-aminosalicylic acid: screening, crystal structures and comparative study of carbamazepine cocrystal formation thermodynamics." CrystEngComm 19, no. 30 (2017): 4273–86. http://dx.doi.org/10.1039/c7ce00831g.

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Yang, Shiying, Qiwen Liu, Weiwen Ji, et al. "Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation." Molecules 27, no. 6 (2022): 2022. http://dx.doi.org/10.3390/molecules27062022.

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Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using t

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