Cocrystal Solubility Research Articles

The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation

Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and Ksp values of 1:1 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolution, cocrystals regulate the interfacial pH (pHint) to 1.6 for MLX-MLE and 4.5 for MLX-SLC, therefore diminishing the cocrystal dissolution rate dependence on bulk pH. Do values ranged from 2 (pH 6.5) to 410 (pH 1.6) and were mostly determined by the drug solubility dependence on pH. Drug release profiles show that maximum supersaturation (σmax=Cmax/Sdrug)and AUC increased with increasing Do as pH decreased. When Do>>SA, the cocrystal solubility is not sufficient to dissolve the dose so that a dissolution-precipitation quasi-equilibrium state is able to sustain supersaturation for the extent of the experiment (24 h). When Do<<SA, cocrystal solubility is more than adequate to dissolve the dose. Low σmax values (1.7 and 1.5) near the value of Do (2.3 and 2.4) were observed, where a large fraction of the cocrystal added is dissolved to reach σmax. Two different cocrystal to drug conversion pathways were observed: (1) surface nucleation of the metastable MLX polymorph IV on the dissolving cocrystal preceeded formation of the stable MLX polymorph I in bulk solution (in all conditions without FeSSIF), and (2) bulk nucleation of the stable MLX polymorph (in FeSSIF). The interplay between cocrystal SA, Do, and drug precipitation pathways provide a framework to interpret and understand the DSP behavior of cocrystals.

Synthesis, Characterization and Morphological Study of Nicotinamide and &lt;i&gt;p&lt;/i&gt;-Coumaric Acid Cocrystal

Cocrystallization is one of the potent methods used to modify the physicochemical properties of drugs. Cocrystal of nicotinamide (NIC):p-coumaric acid (COU) was synthesized by a slow evaporation method using acetonitrile. The cocrystals with different feed molar ratios (NIC:COU : 1:1, 1:2, and 2:1) were characterized using DSC, PXRD, and FTIR, which revealed the formation of different polymorphs for each feed molar ratio. A single crystal of the NIC:COU (1:1) cocrystal was analyzed using single crystal X-ray diffraction (SCD), and 1H-NMR revealed a greater cocrystal structure stability compared to the previously published cocrystal. The intermolecular hydrogen bonds, N-H···O, and O-H···O interactions played a major role in stabilizing the cocrystal structure. A molecular modeling technique was used for prediction and surface chemistry assessment of the morphology showed an elongated (along y-axis) octagonal crystal shape which was in a reasonable agreement with the experimental crystal morphology. The reduction in values of the cocrystal solubility in ethanol was supported by the DSC data and simulation of crystal facets where most the crystal facets exposed to polar functional groups. At the concentration of 31.3 µM, NIC:COU (1:1) cocrystal showed more effective DPPH scavenging with 77.06% increased activity compared to NIC at the same concentration.

Preparation, physicochemical characterization and solubility evaluation of pharmaceutical cocrystals of cinnamic acid

Cocrystals have wide applicability in the field of pharmaceutical sciences, promoting improvements in the physicochemical properties of the drugs. Trans-cinnamic acid (TCA) is a secondary plant metabolite, which has several pharmacological activities and presents as an intrinsic characteristic of low aqueous solubility. The aim of this work was the preparation, characterization and evaluation of solubility of TCA cocrystals. The cocrystals were prepared in 1:1 molar ratio of TCA and coformers, employing the solvent evaporation method. The samples were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The solubility of cocrystals was evaluated by shaker-flask method for 24 h. PXRD data showed the potential formation of three cocrystals, from the appearance of new peaks in the diffraction pattern and discarded the occurrence of polymorphism due to no changes in the crystalline pattern. DSC curves showed that the possibility of potential cocrystals formation is associated with a decrease in the melting temperature of the raw materials isolated in the samples, and the FTIR spectroscopy showed changes in the vibration frequencies of the possible functional groups involved in hydrogen bonding. SEM images showed changes in TCA morphology and coformers in cocrystals. Moreover, the solubility of cocrystals showed a significant increase in the aqueous media. The results showed that it is possible to improve aqueous solubility by obtaining cocrystals.

Comments on “Measurement and correlation of the solubility of estradiol and estradiol-urea co-crystal in fourteen pure solvents at temperatures from 273.15 K to 318.15 K”

The reported study by Ning et al. about measurement and correlation of the solubility of estradiol and estradiol-urea co-crystal in fourteen pure solvents at temperatures from 273.15 K to 318.15 K has been evaluated from viewpoint of the applied method for determination of co-crystal solubility; and the effect of solid transformations in determination of co-crystal solubility has been discussed.

Solubility and Stability Advantages of a New Cocrystal of Berberine Chloride with Fumaric Acid.

BBC is a drug with a variety of activities but poor solubility. Cocrystal technology is an effective method to improve the solubility and stability of this type of compound. In this work, the cocrystal of BBC with fumaric acid was obtained at a stoichiometric ratio of 2:1. Studies on stabilities and solubilities were carried out using BBC dihydrate and tetrahydrate as reference materials. Results showed that this new cocrystal did not only significantly improve the dissolution rate of BBC but also highly improved the stability in high humidity and temperature. Given that the cocrystals formed by BBC as the host molecule were few, different techniques were applied for characterization and structural analyses. Moreover, theoretical calculations were performed on weak interactions, such as hydrogen bonding and π–π stacking interactions, which provided the research data for the study of this kind of cocrystal.

DISSOLUTION ENHANCEMENT OF LANSOPRAZOLE USING COCRYSTALLIZATION

Objective: Lansoprazole (LPZ) is a Biopharmaceutics Classification System Class II drug. It has low solubility and high permeability, so its rate ofdissolution is a rate-limiting step for drug absorption. This study aimed to improve the dissolution rate of LPZ by forming cocrystals, using nicotinamide(NCT) as the conformer.Methods: Cocrystals of LPZ were produced using the solvent evaporation and solvent-drop grinding methods with a molar ratio of 1:1 and 1:2.The cocrystals were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanningcalorimetry (DSC). The solubility and dissolution of the LPZ cocrystals were examined in distilled water.Results: FTIR was used to confirm the formation of hydrogen bonds between LPZ and NCT. DSC and XRD studies showed the formation of crystalsfrom cocrystals and a decrease of the melting point of the cocrystals. The dissolution study revealed that the cocrystals could increase the LPZdissolution rate by up to 8.4-fold compared with pure LPZ.Conclusion: LPZ cocrystal formation with NCT was successful in increasing the dissolution rate of LPZ.

Development of a First-Order Derivative UV Spectrophotometric Method for the Assay and Solubility Evaluation of Lamotrigine and Nicotinamide Cocrystals

Pharmaceutical cocrystals are composed of a drug and a coformer and are currently gaining attention due to their possibility of improving drug solubility. Quantitative determination of cocrystals is usually carried out by liquid chromatography method, but an alternative for the same is derivative UV spectrophotometry. Cocrystals of lamotrigine (LAM) were formed with nicotinamide (NIC) in order to improve the solubility of LAM. The aim of this study was to develop and validate a simple, low-cost, environment friendly, first-order derivative spectrophotometric method for simultaneous determination of LAM and NIC in cocrystals. Determination of LAM and NIC was performed at 244.4 and 271.6 nm, respectively. The method was accurate with recovery values of 98.21-101.52%, and precise (relative standard deviation (RSD) < 1.88%). Robustness evaluated by Plackett-Burman design showed no significant influence of the factors (pH, scanning speed, and sonication time) on LAM and NIC assays. The developed method was compared with a high performance liquid chromatography (HPLC) method and applied to study the cocrystal stoichiometry and solubility. The results indicated a molar ratio of 1:1 and that the cocrystal is more soluble than the drug. This study demonstrated that the first-order derivative method is feasible for drug and coformer determination in cocrystals and is a suitable alternative to chromatographic methods.

Probenecid and benzamide: cocrystal prepared by a green method and its physico-chemical and pharmaceutical characterization

The eco-friendly method of kneading was here used to synthesize a cocrystal of probenecid, an uricosuric drug used in treating gout and hyperuricemia, with the aim to improve its pharmaceutical behavior. Benzamide was selected as a co-former showing functional groups favorable to the formation of supramolecular synthons with the active principle. The kneading product was characterized by a range of experimental techniques (microscopic, spectroscopic, thermal and diffractometric) all proving the formation of the new multicomponent crystal. In particular, the FT-IR and NMR techniques showed that an important change of hydrogen bonds network takes place in the kneading product and that the acid–acid interaction in the pristine drug is replaced with the related acid-amide one in the cocrystal. The cocrystal solubility and dissolution rate measured in several biorelevant fluids showed an actual improvement with respect to the pure drug.

Crystal structures, dissolution and pharmacokinetic study on a novel phosphodiesterase-4 inhibitor chlorbipram cocrystals.

Cocrystallization of chlorbipram (ChBP), a novel phosphodiesterase-4 (PDE) inhibitor with water insoluble property developed in our lab, was performed to improve the physicochemical properties and bioavailability in the present study. Three new cocrystals with fumaric aicd (FA), gentisic acid (GA) and salicylic acid (SA) as coformers were synthesized and fully characterized by using the combination of multi-techniques. The cocrystals are phase stable even under high humidity conditions. In vitro study indicates that the solubility of ChBP-GA and ChBP-SA cocrystals increase to 3724.4 ± 58.7, 2897.4 ± 81.9 μg/mL in comparison with ChBP (2561.3 ± 150.4 μg/mL), the intrinsic dissolution rates (IDRs) of ChBP-GA and ChBP-SA cocrystals (721.3 ± 8.0, 614.4 ± 13.2 μg/min/cm2) are both higher than ChBP (537.9 ± 12.0 μg/min/cm2). The blood concentration peak values of ChBP-GA and ChBP-SA cocrystals (165.8 ± 50.9, 105.3 ± 35.6 ng/mL) are both higher than ChBP (51.3 ± 15.1 ng/mL) in in vivo evaluation. It presents the same order in in vitro/vivo study: ChBP-GA > ChBP-SA > ChBP > ChBP-FA. ChBP-FA cocrystal presents a longer elimination half life (t1/2 = 10.0 ± 2.6 h), which makes it a potential candidate for prolonged controlled release formulation. ChBP-GA and ChBP-SA cocrystals both present enhanced solubility and bioavailability in comparison with ChBP, making them a better candidate for the solid dosage formulation development.

Comparative analysis of experimental methods for determining thermodynamic parameters of formation of multi-component molecular crystals: Benefits and limitations

In this work, we have studied the processes of dissolution of 4-aminobenzoic acid (PABA) two-component crystals with 6-methyluracil (6-MeUr), pyrazinamide (PyrAm) and emoxypine (EMX) in the pH 7.4 phosphate buffer. The thermodynamic functions of cocrystal/salt formation have been estimated from the cocrystal/salt solubility and the corresponding solubility of the pure compounds at various temperatures. By analysing the investigated binary systems, we have compared the accuracy of different experimental methods in evaluating the thermodynamic stability of two PABA cocrystals and one salt: the method of phase solubility diagrams and the cocrystal solubility method. A qualitative evaluation of the comparative stability of the cocrystals and salt has been conducted by the competitive reactions method. The lowest value of the Gibbs energy of formation has been found in the PABA cocrystal with 6-MeUr. The fact that the PABA salt with EMX has the highest absolute value of the Gibbs energy of formation is associated with proton transfer.

Structure determination and in vitro/vivo study on carbamazepine-naringenin (1:1) cocrystal

Cocrystallization between a BCS II class drug, carbamazepine, and polyphenolic compounds such as naringenin and naringin, is performed in the present study. New carbamazepine-naringenin (CBZ-NRG) cocrystal with 1: 1 molar ratio was obtained and characterized by using the methods of X-ray diffraction, nuclear magnetic resonance (solid state 13C-NMRand liquid 1H NMR), thermal and spectral analyses (FT-IR and solid state fluorescence). CBZ-NRG crystallizes in the P21/c space group, which belongs to monoclinic system. The molecular interactions were elaborated in the packing diagrams and confirmed by solid state 13C NMR and FT-IR methods. It is scarce that CBZ-NRG cocrystal presents higher endotherm (Tonset = 272.7 °C) than both starting materials (Tonset = 188.6, 248.6 °C) using DSC analysis. The fluorescence values of CBZ-NRG cocrystal (179 A.U.) decreases significantly in comparison with CBZ (6121 A.U.). The in vitro/vivo assessment of NRG effect on CBZ was conducted in the present study. Compared with CBZ (97.2 ± 1.5 μg/mL) in water the solubility of CBZ-NRG cocrystal decreases to 7.2 ± 0.6 μg/mL, the same trends in pH = 1.2 and 6.8 buffer solution. The IDR values of CBZ and CBZ-NRG cocrystal are 0.042 and 0.016 mg/cm2/min respectively. Interestingly, CBZ has one absorption peak while the CBZ-NRG cocrystal has double absorption peaks in plasma concentration-time curves. The peak concentration (Cmax = 491.3 ± 97.6 ng/mL) of CBZ-NRG cocrystal decreases with longer elimination half life (t1/2 = 8.5 ± 1.0 h) in comparison with CBZ (Cmax = 5258.1 ± 904.2 ng/mL, t1/2 = 0.7 ± 0.2 h). The obtained results suggest that CBZ-NRG cocrystal presents different in vitro/vivo performance in comparison with CBZ.

Experimental Data of Fabricated Co-crystals of Doxorubicin HCl with Flavonoids

Abstract: Objectives: This current research work aimed for improvement of the solubility and permeability of poorly permeable Doxorubicin HCl through generating co-crystals. The main goal for the preparation of oral drugs is to decrease the overall cost of healthcare and route of administration is made easy. Methodology: In this study co-crystals of Doxorubicin HCl with Quercetin hydrate and Naringin has been prepared based on ease of hydrogen bond formation. The co-crystal batches of Doxorubicin HCl-Quercetin hydrate in ratio 1:1, 1:2, 2:1 and Doxorubicin HCl-Naringin in ratio 1:1 are prepared by slow solvent evaporation technique. Results and Discussion: The formation of co-crystal was confirmed by PXRD, DSC and FTIR. Doxorubicin HCl with Naringen crystal batch show improved solubility. The dynamic solubility of Doxorubicin HCl-Naringin co-crystal in the ratios 1:1 increased by approximately 9.2-fold as compared to pure drug and Doxorubicin HCl -Quercetin hydrate cocrystal batches. Key words: Doxorubicin HCl, Quercetin hydrate, Naringin, Cocrystals, HPLC, Solid state characterisation, Saturated solubility.

Designing of Stable Co-crystals of Zoledronic Acid Using Suitable Coformers.

In this present study a new co-crystals of zoledronic acid with DL-tartaric acid and nicotinamide has been developed with improved solubility. Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology. Pharmaceutical cocrystals are multi-component crystals with a stoichiometric ratio of active pharmaceutical ingredients (APIs) and cocrystal coformers (CCFs) that are assembled by noncovalent interactions such as hydrogen bonds, π-π packing, and Vander Waals forces. In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1 : 2 and 2 : 1 increased by fold as compared to pure drug.

Cocrystal Solubility Advantage Diagrams as a Means to Control Dissolution, Supersaturation, and Precipitation.

Cocrystals are often more soluble than needed and pose unnecessary risks for precipitation of less soluble forms of the drug during processing and dissolution. Such conversions lead to erratic cocrystal behavior and nullify the cocrystal solubility advantage over parent drug (SA = Scocrystal/Sdrug). This work demonstrates a quantitative method for additive selection to control cocrystal disproportionation based on cocrystal solubility advantage (SA) diagrams. The tunability of cocrystal SA is dependent on the selective drug-solubilizing power of surfactants (SPdrug = (ST/Saq)drug). This cocrystal property is used to generate SA-SP diagrams that facilitate surfactant selection and provide a framework for evaluating how SA influences drug concentration-time profiles associated with cocrystal dissolution, drug supersaturation, and precipitation (DSP). Experimental results with indomethacin-saccharin cocrystal and surfactants (sodium lauryl sulfate, Brij, and Myrj) demonstrate the log-linear relationship characteristic of SA-SP diagrams and the dependence of σmax and dissolution area under the curve (AUC) on SA with characteristic maxima at a threshold supersaturation where drug nucleation occurs. This approach is expected to streamline cocrystal formulation as it facilitates additive selection by considering the interplay between thermodynamic (SA) and kinetic (DSP) processes.

Isoniazid-Resveratrol Cocrystal: A Novel Alternative for Topical Treatment of Cutaneous Tuberculosis

The current treatment for cutaneous tuberculosis consists of oral coadministration of isoniazid (INH) and rifampicin, which is often related to hepatotoxic events. Alternatively, INH could be administered on the skin aiming to avoid or minimize these side effects. The high cutaneous permeation of this drug motivated the obtainment of a cocrystal of INH and resveratrol (RES), a lipophilic compound, to provide a local effect. In this study, isoniazid–resveratrol cocrystal (INH-RES) was synthesized by reaction crystallization method, and its structure was determined from single-crystal X-ray diffraction data. Cocrystal, drug, and coformer aqueous solubility was determined in the initial pH range from 1.2 to 7.4. Mathematical models based on cocrystal constituent ionization constants (pKa), solution pH, and cocrystal solubility product (Ksp) were used to generate solubility diagrams as a function of pH. At all pH values studied, INH-RES was less soluble than INH. Permeation studies were performed with drug an...

Synthesis, Crystal Structure, and Solubility Analysis of a Famotidine Cocrystal

A novel cocrystal of the potent H2 receptor antagonist famotidine (FMT) was synthesized with malonic acid (MAL) to enhance its solubility. The cocrystal structure was characterized by X-ray single crystal diffraction, and the asymmetry unit contains one FMT and one MAL connected via intermolecular hydrogen bonds. The crystal structure is monoclinic with a P21/n space group and unit cell parameters a = 7.0748 (3) Å, b = 26.6502 (9) Å, c = 9.9823 (4) Å, α = 90, β = 104.2228 (12), γ = 90, V = 1824.42 (12) Å3, and Z = 4. The cocrystal had unique thermal, spectroscopic, and powder X-ray diffraction (PXRD) properties that differed from FMT. The solubility of the famotidine-malonic acid cocrystal (FMT-MAL) was 4.2-fold higher than FMT; the FAM-MAL had no change in FMT stability at high temperature, high humidity, or with illumination.

Solubility and thermodynamics of probenecid-4,4′-azopyridine cocrystal in pure and binary solvents

Cocrystals of probenecid-4,4′-azopyridine (2:1) form I were first prepared by cooling cocrystallization method and characterized by scanning electron microscope (SEM), optical microscopy, powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FT-IR). The solubility of cocrystal form I in six pure solvents and two binary solvents with temperature from 273.15 K to 313.15 K was measured by using a gravimetric method. Solubility of cocrystals increases when the temperature rises in pure and both of binary solvents. In pure solvents, the solubility of cocrystals form I from largest to smallest follows the order acetone > ethyl acetate > ethanol ≈ 1-propanol ≈ 2-propanol > acetonitrile. The modified Apelblat equation, λh equation and NRTL model were used to the correlate solubility data in pure solvents and those three models plus CNIBS/Redlich-Kister model and modified Jouyban-Acree model were chosen to correlate the solubility data in two binary solvents. All models provide great correlation and accuracy. Besides, apparent dissolution enthalpy, entropy and Gibbs energy were obtained through NRTL model and the result shows that in six pure and two binary solvents, the process of dissolution of form I of probenecid-4,4′-azopyridine cocrystals is spontaneous, endothermic and driven by entropy.

Investigation of possible solubility and dissolution advantages of cocrystals, I: Aqueous solubility and dissolution rates of ketoconazole and its cocrystals as functions of pH.

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 acids or NaOH. Similar pH-solubility profiles were obtained whether free base or cocrystals were used as starting materials to determine solubility. With the addition of fumaric and succinic acids to aqueous suspensions of free base to lower pH, the maximum solubility (pHmax) was reached at pH ~3.5-4.0, below which the solubility decreased and cocrystals formed. The solubility, however, continued increasing when HCl was added to ketoconazole suspension as no cocrystal or salt was formed. During determination of cocrystal solubility, a conversion to free base was observed when pH was raised above pHmax. Thus, pH-solubility profiles of cocrystals resembled solubility profiles commonly encountered with salts. Above pHmax, both free base and cocrystal had similar solubility under identical pH conditions; the solubility of cocrystal was higher only if the pH differed. In contrast, intrinsic dissolution rates of cocrystals at pH>pHmax under identical bulk pH were much higher than that of free ketoconazole since cocrystals had lower microenvironmental pH at the dissolving surface, where the solubility was high. Thus, cocrystals of basic drugs can potentially provide higher dissolution rates under intestinal pH conditions.

The effect of surfactant and polymer on solution stability and solubility of tadalafil-methylparaben cocrystal

Cocrystal formation is a novel method to enhance physicochemical properties of pharmaceuticals. However, instability in solution is one of the challenging issues of cocrystals and surfactants/polymers could have a positive effect on cocrystal solubility and stability. In this study, tadalafil cocrystal was prepared via the solvent drop grinding method with methylparaben as a cocrystal former. The thermodynamic solubility of cocrystal was determined in phosphate buffer solution (pH = 6.8) and in the presence of different concentrations of sodium lauryl sulfate (SLS) and polyvinylpyrrolidone (PVP), followed by investigating their effects on solution stability of cocrystal. The prepared cocrystal showed enhancement in solubility compared with tadalafil, but the solution stability analysis indicated it is an incongruently saturating cocrystal that could transform to a less soluble solid form during slurring and dissolution. Moreover, PVP and SLS improved the cocrystal solution stability, however, the solubility advantage for the prepared cocrystal is not obtained because of preferential solubilization for tadalafil that is less soluble than methylparaben. Overall, the results showed that cocrystal formation of tadalafil with methylparaben has the ability to change its physicochemical properties. In addition, polymer and surfactant could have a significant effect on the solubility and the stability of the cocrystal.

Glibenclamide-Nicotinamide Cocrystals Synthesized by The Solvent Evaporation Method to Enhance Solubility and Dissolution Rate of Glibenclamide

Purpose: To develop glibenclamide-nicotinamide cocrystals with the solvent evaporation method and evaluate their solubility and dissolution properties. Methods: Cocrystals of glibenclamide-nicotinamide (1:2) were prepared with the solvent evaporation method. The prediction of interactive cocrystals was observed using in silico method. The solubility and dissolution were performed as evaluation of cocrystals. The cocrystals also were characterized by differential scanning calorimetry (DSC), infrared spectrophotometry, and powder X-ray diffraction (PXRD). Result: The solubility and dissolution profile of glibenclamide-nicotinamide cocrystal (1:2) increased significantly compared to pure glibenclamide as well as its physical mixture. Characterization of cocrystal glibenclamide-nicotinamide (1:2) including infrared Fourier transform, DSC, and PXRD, indicated the formation of a new solid crystal phase differing from glibenclamide and nicotinamide. Conclusion: The confirmation of cocrystal glibenclamide-nicotinamide (1:2) indicated the formation of new solid crystalline phases that differ from pure glibenclamide and its physical mixture