Multicomponent Crystals Research Articles

Multicomponent crystals: Solubility enhancement of simvastatin using arginine and glycine coformers

Context: Simvastatin can be modified by the formation of multicomponent crystals to increase its solubility. Aims: To compare the solubility of multicomponent simvastatin crystals to pure simvastatin. Methods: The in silico study of simvastatin and the coformers arginine and glycine revealed non-covalent interactions, so multicomponent preparations of simvastatin crystals were prepared by solvent evaporation using a mole ratio of 1:1; 1:2 and 2:1. Results: Each simvastatin-arginine and simvastatin-glycine ratio increased the solubility, with the highest increase observed for the 1:2 ratio compared to pure simvastatin. Conclusions: Simvastatin-arginine multicomponent crystals (1:2) showed the best dissolution profile in phosphate buffer medium pH 7.0 with 67.69% dissolution, while simvastatin-glycine multicomponent crystals (1:2) exhibited the best dissolution profile in buffer media pH 1.2 with 16.19% dissolution. Characterization of the multicomponent crystals revealed a shift in the peaks, a decreased melting point, and enthalpy, indicating decreased % crystallinity and the formation of a new solid phase.

Virtual Screening, Polymorphism, and Formation Thermodynamics Study of Riluzole Multicomponent Crystals with Dihydroxybenzoic Acids

Virtual Screening, Polymorphism, and Formation Thermodynamics Study of Riluzole Multicomponent Crystals with Dihydroxybenzoic Acids

Transition state of matter in the fluctuation model of crystal growth

Two mechanisms of the effect of the transition state of building particles (activated complexes according to S. Arrhenius) on the crystal growth rate within the framework of the fluctuation model of dislocation crystal growth are discussed. Transition state clusters adsorbed on the surface of the growing face perform the function of an impurity that lowers the surface energy of the crystal at the time moments between free energy fluctuations. Thus, the transition state of the crystallizing substance by the first mechanism affects the relaxation rate of the secondary adsorption of impurities and shortens the time period of attachment of building particles to the crystal face. Other clusters formed in solution reduce the number of free particles and under conditions of low concentration of the building substance are able to decrease the crystallization rate. Nevertheless, in a natural multicomponent crystallization environment, at low concentrations of building material, significant thermal effect of crystallization and small deviations from equilibrium, the role of the transition state in crystal growth is generally insignificant.

Crystal structures of two different multi-component crystals consisting of 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline and fumaric acid

Two different multi-component crystals consisting of papaverine [1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, C20H21NO4] and fumaric acid [C4H4O4] were obtained. Single-crystal X-ray structure analysis revealed that one, C20H21NO4·1.5C4H4O4 (I), is a salt co-crystal composed of salt-forming and non-salt-forming molecules, and the other, C20H21NO4·0.5C4H4O4 (II), is a salt–co-crystal intermediate (i.e., in an intermediate state between a salt and a co-crystal). In this study, one state (crystal structure at 100 K) within the salt–co-crystal continuum is defined as the ‘intermediate’.

Hydrogen-Bonded Ionic Co-Crystals for Fast Solid-State Zinc Ion Storage.

The development of new ionic conductors meeting the requirements of current solid-state devices is imminent but still challenging. Hydrogen-bonded ionic co-crystals (HICs) are multi-component crystals based on hydrogen bonding and Coulombic interactions. Due to the hydrogen bond network and unique features of ionic crystals, HICs have flexible skeletons. More importantly, anion vacancies on their surface can potentially help dissociate and adsorb excess anions, forming cation transport channels at grain boundaries. Here, it is demonstrated that a HIC optimized by adjusting the ratio of zinc salt and imidazole can construct grain boundary-based fast Zn2+ transport channels. The as-obtained HIC solid electrolyte possesses an unprecedentedly high ionic conductivity at room and low temperatures (≈11.2 mScm-1 at 25°C and ≈2.78mScm-1 at -40°C) with ultra-low activation energy (≈0.12eV), while restraining dendrite growth and exhibiting low overpotential even at a high current density (<200mV at 5.0mAcm-2) during Zn symmetric cell cycling. This HIC also allows solid-state Zn||covalent organic framework full cells to work at low temperatures, providing superior stability. More importantly, the HIC can even support zinc-ion hybrid supercapacitors to work, achieving extraordinary rate capability and a power density comparable to aqueous solution-based supercapacitors. This work provides a path for designing facilely prepared, low-cost, and environmentally friendly ionic conductors with extremely high ionic conductivity and excellent interface compatibility.

Eutectic mixtures of nevirapine: Phase diagrams, solid-state characterization, and dissolution studies

Solid-state modifications can improve drug performance. Studies have shown that multicomponent crystals, such as cocrystals and eutectic compositions, have successfully improved the performance of certain drugs, including their solubility. Nevirapine (NEV) is an antiretroviral drug with low aqueous solubility, impacting its bioavailability. This work aimed to study different nevirapine/co-former solid eutectic systems, define their phase diagrams and evaluate their dissolution properties. Caffeine (CAF), Theobromine (TEOB), and Theophylline (THEO) were chosen as co-formers due to their functional groups that can interact with NEV. Aiming to determine both temperature and eutectic composition, phase and Tamman diagrams were obtained using the differential scanning calorimetry (DSC) analysis of the mixtures indifferent NEV-co-former compositions (%w/w). Powder X-ray diffraction (PXRD) and DSC were used to characterize the eutectic materials. To assess the influence of eutectic systems on dissolution properties, we determined the powder dissolution profiles and intrinsic dissolution rates of anhydrous NEV and eutectic systems NEV-CAF and NEV-THEO using different dissolution media (pH 1.2 and pH 6.8). The eutectic compositions were calculated through the phase diagrams, interpolating the curves obtained by linear regression. Thus, the eutectic composition of the NEV-CAF system was determined to be 36.55 % NEV and eutectic temperature at 201.1 °C, while in the NEV-THEO system, the eutectic was obtained in a composition of 71.04 % NEV and eutectic temperature at 217.8 °C. Tamman diagrams were generated using the enthalpy values obtained from the DSC curves, and eutectic compositions were calculated using linear regression. The analysis revealed a eutectic composition of 36.51 % of NEV for the NEV-CAF system, and a eutectic composition of 70.94 % of NEV for the NEV-THEO system. It was not possible to determine the eutectic mass fraction of NEV-TEOB. A comparison of dissolution profiles and intrinsic dissolution rates in different dissolution media showed a significant improvement in the NEV dissolution rate in both eutectic systems. In an acidic medium, NEV dissolved 16 times faster in the NEV-CAF sample and 4 times faster in the NEV-THEO sample compared to pure anhydrous NEV. In a neutral medium, the dissolution profile of NEV was even more favorable in the same eutectic systems, showing that the increase in dissolution is relevant in a wide range of pH. In addition, the intrinsic dissolution rate in the two eutectic systems was higher than that of anhydrous NEV in all employed dissolution mediums. These eutectic systems improve the dissolution rate compared to pure NEV, offering the potential for enhancing the dissolution of poorly water-soluble drugs in the future.

Thermodynamic characteristics of multi-component crystals: Experimental evaluation, prediction and relationship with crystal parameters

In this study, we have analyzed the thermodynamic formation functions for four multi-component crystals based on the solubility data in the range of 293.15–313.15 K. The investigation was performed for the cocrystals of fluconazole (FLZ) with 4-hydroxybenzoic (4OHBA) and vanillic (VA) acids, and salts of fenbendazole (FNB) with maleic (Mal) and oxalic (Ox) acids. A database on the thermodynamic parameters of the multi-component molecular crystals (Gibbs free energy, enthalpy, and entropy) obtained in this study and borrowed from the literature was created. These parameters were determined using the experimental data on the solubility of the individual components and the product of the solubilities of the multi-component crystals at 298.15 K. A regression model was proposed to estimate the solubility product of the two-component crystals using the intrinsic solubility of the individual components as an independent variable. A detailed analysis of the database disclosed the relationship between the entropy term and the molecular volume of the multi-component crystal formation.

Multi-component Crystal Strategy for Improving Water Solubility and Antifungal Activity of Climbazole.

The primary problem with climbazole (CLB), a broad-spectrum imidazole antifungal drug, is its low water solubility. In order to increase its water solubility and antifungal activity, three new multi-component crystals were synthesized in this work, and the intermolecular interactions were systematically studied. This work helps to optimize the CLB product formulation and extend its application prospects. In this work, three novel multi-component crystals, CLB-malonic acid (CLB-MA) salt, CLB-succinic acid (CLB-SA) cocrystal and CLB-adipic acid (CLB-AA) cocrystal, were successfully synthesized. And the crystal structure, thermodynamic properties, solubility, dissolution, hygroscopicity, and antifungal activity of the three multi-component crystals were fully characterized by single-crystal X-ray diffraction (SCXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic water vapor adsorption (DVS) and powder dissolution tests, etc. The molecular interactions and molecular stacking in multi-component crystals were studied by Hirshfeld surface (HS), molecular surface electrostatic potential (MEP), interaction region indication (IRI) and atom and molecule (AIM) techniques. The results show that the three multi-component crystals have good moisture resistance stability, and their water solubility is 6-22 times that of pure CLB. Meanwhile, the measurement of the minimum inhibitory concentration (MIC) proves that the cocrystal/salt has a stronger antifungal activity than climbazole. Quantum chemistry calculations of crystal structure visualized and quantified the interactions that exist in multi-component crystals, and explored the microscopic mechanisms underlying the different performance of multi-component crystals.

Supramolecular self-assembly strategy for the enhanced solubility/dissolution rate and anti-cancer efficacy of osimertinib: Insights from multi-component crystals to drug chemistry

Multi-component crystal based on supramolecular self-assembly is an effective strategy to modify the physicochemical properties of poorly water-soluble drugs. In this study, eight novel multi-component crystals of Osimertinib (AZD) were firstly synthesized under the guidance of theoretical analysis. Five single crystals were successfully obtained, and the AZD-FMS cocrystal shows a distinctive structure wherein free FMS filled in the skeleton, which may be crucial for maintaining morphology. Analysis of crystal structures and Hirshfeld surfaces indicated the involvement of N−H···O and N···H−O hydrogen bonds in the multi-component crystals. Owing to robust intermolecular interactions, multi-component crystals exhibited improved solubility/dissolution rate compared to pure AZD. Multivariate analysis revealed coformers and strong solute–solvent interactions determined the solubility/dissolution rate. Multi-component crystals showed superior stability in solution and low humidity. Moreover, AZD-FSM increased 5.2-fold anti-tumor activity over AZD, which is anticipated to enhance efficacy, reduce drug toxicity, combat drug resistance, and transform from laboratory to clinical application.

Jahn-Teller effect and features of divalent copper ion behavior in multicomponent borate crystals

Crystals of YGa3(BO3)4, YAl3(BO3)4, EuGa3(BO3)4 and EuAl3(BO3)4 with copper alloy were studied by electron paramagnetic resonance and X-ray diffraction analysis. The lattice parameters and coordinates of copper-doped boron atoms were determined. The study of EPR spectra showed that copper is in the divalent state and replaces aluminum ions with C2 node symmetry. In YAl3(BO3)4:Cu crystals, a ligand structure exists due to the interaction of copper electrons with yttrium nuclei. The parameters of the spin Hamiltonian describing the behavior of the Cu2+ spectrum have been determined. The deviation of the Z-axis spectra from the C3 axis by 54(1)° is due to Jahn-Teller vibronic interaction and monoclinic distortion. In the EuGa3(BO3)4 crystal, a new spectrum 2 was found, which also belongs to divalent copper but is observed at an excited state 31 cm−1 away from the ground state. Above 70 K, an isotropic EPR line with a width of 450 Gs, g = 2.1, appears and exists up to room temperature.

Supramolecular architectures in multicomponent crystals of imidazole-based drugs and trithiocyanuric acid.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N-H...N hydrogen bond is responsible for the formation of acid-base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N-H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

Ketoprofen-Tromethamine: Binary Phase Diagram of Multicomponent Crystal, Dissolution Rate, and Analgesic Activity Evaluation

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) whose formulation options are limited due to its low dissolution rate in aqueous media. This research aimed to enhance the solubility of ketoprofen in distilled water and to compare the anti-inflammatory and analgesic effects of its resulting multicomponent crystal with tromethamine. The binary phase diagram of ketoprofen-tromethamine was created across molar ratios ranging from 1:9 to 9:1. The multicomponent crystal comprising ketoprofen and tromethamine in the selected ratio was synthesized using a solvent drop grinding method and subjected to further characterization for thermal properties, crystallinity, chemical groups, and morphology. The dissolution rate assessments were evaluated in CO2-free distilled water. Pharmacological analyses examined the anti-inflammatory and analgesic effects of the multicomponent crystal. The binary phase analysis identified the 5:5 (1:1) molar ratio as optimal in forming a multicomponent crystal. Thermograms and diffractograms revealed crystalline alterations attributed to a new crystalline phase. The new multicomponent crystal exhibited approximately 2.7 times higher dissolution rate after 30 minutes, outperforming pure ketoprofen. Pharmacological assessments demonstrated superior analgesic effects of the multicomponent crystal. In summary, the ketoprofen-tromethamine cocrystal in 1:1 molar ratio offers enhanced dissolution rate and provides better analgesic activity than ketoprofen alone.

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.

Crystal structure and Hirshfeld surface of a pentaaminecopper(II) complex with urea and chloride

The reaction of copper(II) oxalate and hexamethylenetetramine in a deep eutectic solvent made of urea and choline chloride produced crystals of pentaaminecopper(II) dichloride–urea (1/1), [Cu(NH3)5]Cl2·CO(NH2)2, which was characterized by single-crystal X-ray diffraction. The complex contains discrete pentaaminecopper(II) units in a square-based pyramidal geometry. The overall structure of the multi-component crystal is dictated by hydrogen bonding between urea molecules and amine H atoms with chloride anions.

Preparation and Structures of Multicomponent Crystals Composed of Heteroaromatic Cations, p‐Toluenesulfonate Anion, and Aromatic Hydrogen‐Bond Donors

AbstractCocrystals with three π‐components, which were a π‐cation, a π‐anion acting as a hydrogen‐bond acceptor, and a π‐molecule acting as a hydrogen‐bond donor, were prepared by the solution‐growth methods. The first and second components were ion pairs of 1‐methylpyridinium or 1‐methylquinolinium p‐toluenesulfonate derivatives, and the third components were dihydric phenol derivatives, like hydroquinone, 1,4‐naphthalenediol, 4,4’‐biphenol, and 1,1’‐bi‐2‐naphthol, or benzoic acid derivatives with hydroxy or amino group at the para position. Among 23 cocrystals found from 35 possible combinations of five ion‐pairs and seven hydrogen‐bond donors, 20 cocrystals were investigated by the X‐ray crystallographic analyses. Some of them also contained solvent molecules. In these cocrystals, hydrogen‐bond sequences composed of p‐toluenesulfonate and the hydrogen‐bond donors were observed, and ionic bonds between the first and second components and hydrogen bonds between the second and third components were found to be responsible for three‐π‐component cocrystals. When the cations were 4‐cyanopyridinium or quinolinium derivatives, the cocrystals showed charge‐transfer absorption bands due to electronic interaction between the cations and the hydrogen‐bond donors. To the mixture of quinolinium p‐toluenesulfonate and 1,1’‐bi‐2‐naphthol forming the three‐π‐component cocrystals, tetrathiafulvalene were added to form four‐π‐component cocrystals with ethanol or water molecules.

Sensitizing Explosives Through Molecular Doping.

Cocrystallization assembles multicomponent crystals in defined ratios that are held together by intermolecular interactions. While cocrystals have seen extensive use in the pharmaceutical industry for solving issues with stability and solubility, extension to the field of energetic materials for improved properties has proven difficult. Predicting successful coformers remains a challenge for systems lacking well-understood synthons that promote reliable intermolecular assembly. Herein, an alternative method is investigated for altering energetic properties that operates in the absence of well-defined interactions by molecular doping. An impact sensitive primary explosive, cyanuric triazide (CTA), was selected as the dopant to test if less impact sensitive secondary explosives could gain increased sensitization to impact when CTA is inserted into their crystal lattices. Molecular doping was successful in sensitizing three melt-castable energetics: 2,4,6-trinitrotoluene (TNT), 2,4-dinitroanisole (DNAN), and 1,3,3-trinitroazetidine (TNAZ). CTA could also be incorporated as a stabilized inclusion to sensitize DNAN further. These results demonstrate how the judicious choice of dopant can lead to specific property improvements, providing a method for creating energetic materials with new properties to access metal-free primary explosives and physical hot spot models for explosive ignition.

TENOXICAM-TROMETHAMINE MULTICOMPONENT CRYSTAL: PHYSICOCHEMICAL CHARACTERISTICS, SOLUBILITY, AND DISSOLUTION EVALUATION

Objective: Tenoxicam is classified as a nonsteroidal anti-inflammatory drug employed for managing musculoskeletal conditions. However, its effectiveness is obstructed by its restricted ability to dissolve in water. This investigation aims to create a multicomponent crystal involving tenoxicam and tromethamine to augment tenoxicam's solubility and dissolution rate.&#x0D; Methods: Using the solvent drop grinding technique, the multicomponent crystal was synthesized by combining tenoxicam and tromethamine in equimolar proportions. The physicochemical properties of multicomponent crystal were assessed through powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and FT-IR spectroscopy. Solubility test and dissolution rate profile were conducted to evaluate the effectiveness of multicomponent crystal formation in compared to intact tenoxicam. The solubility test occurred in CO2-free distilled water over 48 h and was quantified using UV spectrophotometry at 368 nm. Dissolution rate profiles were conducted using a USP type II dissolution apparatus in HCl 0.1 N, and CO2-free distilled water as the dissolution media.&#x0D; Results: The multicomponent crystal displayed distinctive characteristics in the diffractogram, including altered melting points, and shifts in the FT-IR spectrum peaks. Within the multicomponent crystal system, the solubility of tenoxicam exhibited a notable increase, specifically by a factor of 11.130. Moreover, the dissolution efficiency of tenoxicam in HCl 0.1 N solution and CO2-free distilled water showed substantial enhancements, with respective increases of 2.600-fold and 8.605-fold observed at the 60-minute mark.&#x0D; Conclusion: In conclusion, the tenoxicam and tromethamine multicomponent crystal formation using a solvent drop grinding technique resulted in a novel crystalline structure, enhancing the solubility and dissolution of tenoxicam both in CO2-free distilled water and HCl 0.1 N.

PREPARATION OF SPRAY-DRIED MULTICOMPONENT CRYSTALS OF TRIMETHOPRIM-MANDELIC ACID AND ITS PHYSICOCHEMICAL CHARACTERIZATION

Objective: Trimethoprim is a wide-spectrum antimicrobial compound belonging to Class II of the Biopharmaceutics Classification System (BCS), with high permeability but low solubility. This study aimed to prepare a multicomponent crystal (MCC) of trimethoprim-mandelic acid to enhance the solubility of trimethoprim.&#x0D; Methods: MCC trimethoprim–mandelic acid was prepared by spray drying technique. Solid-state characterizations were performed by using PowX-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier-transform infrared (FT IR) spectroscopy, Scanning Electron Microscopy (SEM), and polarized microscopy. The solubility test was performed in distilled water. The amount of dissolved trimethoprim was analyzed by High-Performance Liquid Chromatography (HPLC) using acetonitrile and phosphoric acid 1 % (10:90 v/v) as the mobile phase.&#x0D; Results: MCC characterizations showed a different diffraction pattern from its intact materials according to PXRD analysis, a decrease in the melting point in the DSC thermogram, a shift of the wave number in the FT-IR spectra, and a new crystalline habit compared to the intact materials was presented by SEM analysis. The MCC also showed the color of interference under polarized microscopy, indicating the crystalline phase. The solubility of trimethoprim in MCC increased significantly by 3.98 times in comparison to intact trimethoprim.&#x0D; Conclusion: The MCC trimethoprim-mandelic acid by spray drying technique enhanced the solubility of trimethoprim.

INCREASED DISSOLUTION RATE OF ACECLOFENAC BY FORMATION OF MULTICOMPONENT CRYSTALS WITH L-GLUTAMINE

Objective: The objectives of this research were to improve the solubility as well as the rate of dissolution of aceclofenac (ACF) through the formation of multicomponent crystals (MCC) with L-glutamine (LGLN) as a coformer and following the liquid-assisted grinding (LAG) technique.&#x0D; Methods: MCC of ACF and LGLN was formed by Liquid Assisted Grinding (LAG) technique. Powder X-ray Diffractometer (PXRD), Differential Scanning Calorimeter (DSC), Fourier Transform Infrared (FT-IR) spectrometer, Particle Size Analyzer (PSA), and Scanning Electron Microscope (SEM) were used for MCC characterization. Solubility and dissolution test were determined using ultraviolet-visible (Uv-Vis( spectrophotometer.&#x0D; Results: The results showed a decrease in the diffraction peak intensity, melting point, and enthalpy of fusion. FT-IR analysis showed a non-significant wavenumber shift compared to intact components. These characterizations showed that MCC formed a eutectic mixture. SEM and particle size analysis showed a homogeneous particle rod shape and decreased particle size. ACF's solubility in MCC increased 2.21 times more than intact form. MCC's dissolution rate increased by 5.34 times and 5.56 times, respectively, after 60 min in phosphate buffer pH 6.8 and CO2-free distilled water.&#x0D; Conclusion: The formation of MCC of ACF and LGLN considerably enhances ACF's solubility and dissolution rate.

Efficient cocrystal coformer screening based on a Machine learning Strategy: A case study for the preparation of imatinib cocrystal with enhanced physicochemical properties

Cocrystal engineering, which involves the self-assembly of two or more components into a solid-state supramolecular structure through non-covalent interactions, has emerged as a promising approach to tailor the physicochemical properties of active pharmaceutical ingredient (API). Efficient coformer screening for cocrystal remains a challenge. Herein, a prediction strategy based on machine learning algorithms was employed to predict cocrystal formation and seven reliable models with accuracy over 0.890 were successfully constructed. Imatinib was selected as the model drug and the models established were applied to screen 31 potential coformers. Experimental verification results indicated RF-8 is the optimal model among seven models with an accuracy of 0.839. When the seven models were combined for coformer screening of Imatinib, the combinational model achieved an accuracy of 0.903, and eight new solid forms were observed and characterized. Benefiting from intermolecular interactions, the obtained multicomponent crystals displayed enhanced physicochemical properties. Dissolution and solubility experiments showed the prepared multicomponent crystals had higher cumulative dissolution rate and remarkably improved the solubility of imatinib, and IM-MC exhibited comparable solubility to Imatinib mesylate α form. Stability test and cytotoxicity results showed that multicomponent crystals exhibited excellent stability and the drug-drug cocrystal IM-5F exhibited higher cytotoxicity than pure API.