Acid Cocrystal Research Articles

Mechanofluorochromic Anthryl Phosphonate/Benzoic Acid Cocrystals with a Large Blue Shift: The Role of P=O⋅⋅⋅H Interactions.

Organophosphonates have a rich and diverse chemistry, but their mechanofluorochromic features have rarely been documented. Herein, we report on cocrystals of anthranylphosphonate with (E)-4-(2-(anthracen-9-yl)vinyl)benzoic acid that exhibit reversible mechanofluorochromic properties with large blue shifts. Anisotropic grinding (or pressure of just 25 kPa) maintains the co-crystals emission features but leads to a pronounced 59 nm (2087 cm-1 ) blue-shift. Such an impressive blue-shift for a cocrystal has not been reported to date. The underlying causes for the blue-shift were validated by X-ray diffraction (powder and single crystal) studies and Hirshfeld surface analysis. Twisted molecular conformations and P=O⋅⋅⋅ H/C=O⋅⋅⋅H/C⋅⋅⋅H noncovalent interactions afford molecular arrangements via slip-stacks with two different pitch angles and relatively larger interlayer distances. The new compound was established as a potential medium for optical recording and security display.

Novel curcumin ascorbic acid cocrystal for improved solubility

The present investigation aims to develop novel curcumin-ascorbic acid cocrystal for enhancing the solubility, stability, and complementary biological activities for curcumin. Based on in silico approach to screen ascorbic acid as a coformer for curcumin, cocrystals were prepared by the solvent evaporation method, and further evaluated for saturation solubility, cocrystal propensity, physicochemical interactions (FTIR and DSC), XRD, drug dissolution, etc. In silico findings confirmed the suitability (H_ex, G_mix) of ascorbic acid for the cocrystallization of curcumin. The DSC and XRD data of the solvent evaporated curcumin-ascorbic acid mixture confirmed the formation of cocrystal, eutectic, and binary mixture with an excess of coformer. The binary phase diagram implied 0.5 to the 0.65-mole fraction of curcumin, essential for cocrystallization with ascorbic acid. The novel curcumin ascorbic acid cocrystals revealed extraordinary improvement in aqueous solubility of curcumin, especially, 576 fold in distilled water, 10 fold in the buffer pH 1.2, and 9 fold in the buffer pH 6.8. The curcumin-ascorbic acid cocrystal system exhibited a superior dissolution profile compared to neat curcumin. Thus, ascorbic acid has enunciated its role as a coformer for curcumin in cocrystal formation, which has been complemented by predicted complementary biological activities, and stability (acidic milieu).

Discovery, Characterization, and Pharmaceutical Applications of Two Loratadine–Oxalic Acid Cocrystals

Loratadine (Lor) is an antihistamine drug commonly used to relieve the symptoms of allergy. It has high permeability but low solubility under physiological conditions. To overcome the problem of low solubility, we synthesized and characterized two Loratadine multi-component crystalline phases with oxalic acid (Oxa), i.e., a 1:1 Lor-Oxa conjugate acid-base (CAB) cocrystal (Lor-Oxa CAB) and a 2:1 Lor-Oxa cocrystal monohydrate (Lor-Oxa hydrate). Both cocrystals exhibited an enhanced solubility and intrinsic dissolution rate (IDR) compared to Lor and adequate physical stability. The intrinsic dissolution rate of Lor-Oxa CAB is 95 times that of Lor, which makes it a promising candidate for tablet formulation development.

Solid-State Competitive Destabilization of Caffeine Malonic Acid Cocrystal: Mechanistic and Kinetic Investigations

The main objective of this research is to investigate both the mechanism and the kinetics of solvent-free destabilization of the model caffeine/malonic acid cocrystal (CA/MO 2:1) in the presence of oxalic acid (OX) as a structural competitor to malonic acid (MO). Competitive destabilization of CA/MO and subsequent formation of caffeine/oxalic acid (CA/OX) take place at temperatures significantly below their melting points. The destabilization mechanism was found to be mediated by sublimation of both CA/MO and OX. During CA/MO destabilization, free CA could not be detected, and direct transformation to the CA/OX cocrystal was observed. The destabilization kinetics follow Prout–Tompkins nucleation and the crystal growth model with an activation energy of 133.91 kJ/mol, and subsequent CA/OX growth kinetics follow Ginstling–Brounshtien and three-dimensional diffusion models with an activation energy range of 130.45–132.57 kJ/mol.

Development of piroxicam mini-tablets enabled by spherical cocrystallization.

We examined the potential of the spherical cocrystallization (SCC) technology in simultaneously enhancing tablet manufacturability and dissolution of poorly soluble drugs by developing a mini-tablet formulation of piroxicam. The manufacturing of mini-tablets using a direct compression (DC) process is more challenging than conventional tablets because of the much stricter requirement on the micromeritic properties of formulated powders. The SCC process in this work involved two steps: 1) preparing a new piroxicam-ferulic acid (PRX-FA) cocrystal, and 2) forming spherical agglomerates with the aid of a suitable bridging liquid. The PRX-FA cocrystal exhibited enhanced solubility as well as improved plasticity. The bridging liquid, a mixture of chloroform and ethyl acetate (EA) (1: 2, v/v), was chosen based on the high computed adsorption energy of chloroform and EA on morphologically dominating crystal faces of PRX-FA. The improved flowability, tabletability, and dissolution rate of spherical PRX-FA enabled the successful development of a DC mini-tablet formulation with a high PRX loading (41wt%). This example shows that SCC is a powerful enabling technology for DC tablet formulation development of challenging drugs.

Novel cocrystals of brexpiprazole with improved solubility

Brexpiprazole (BPZ) is a typical antipsychotic drug used for the treatment of schizophrenia and depression. It is classified under BCS class-II with low aqueous solubility and high intestinal permeability. In the present investigation, we reported novel solid forms of brexpiprazole with acid coformers such as glutaric acid (GLU), fumaric acid (FUM), malonic acid (MAL) and succinic acid (SUC) via solvent drop grinding method. All the cocrystals were completely characterized by PXRD (Powder X-ray Diffraction), DSC (Differential Scanning Calorimetry) and FTIR (Fourier Transform Infrared Spectroscopy). The crystal structure is determined for malonic acid cocrystal by single-crystal X-ray diffraction method. The crystal structure revealed that the cocrystal crystallized in the triclinic crystal system with space group P-1 and the malonic acid molecules are sandwiched by brexpiprazole molecules. The solubility studies for brexpiprazole and cocrystals are established in 0.05 M acetate buffer with pH 4.3 at 25 ± 2 °C. Among all solid forms BPZ:FUM cocrystal shown 2.6 times higher solubility than parent drug whereas other cocrystals such as BPZ:GLU, BPZ:SUC and BPZ:MAL improved by 1.77, 1.59 and 1.37 times.

Evidence of low temperature phase transition in 2,6-dimethylpyrazine - picric acid cocrystal by means of temperature dependent investigations: X-ray, DSC and IR

In the present paper the structural and dynamical properties of crystalline 2,6–dimethylpyrazine - picric acid cocrystal are described. The title cocrystal crystallizes in centrosymmetric monoclinic P21/c space group. The X-ray diffraction and NMR spectroscopy show the presence of protonated form of 2,6-dimethypyrazine and deprotonated form of picric acid molecules. The Hirshfeld surface analysis for determine of intermolecular contacts was performed. Low temperature phase transition was observed and described by temperature dependent investigations: X-ray diffraction, different scanning calorimetry (DSC) and IR spectroscopy. The vibrational properties of cocrystal were investigated by use of IR and Raman spectroscopies, as well as density functional theory (DFT) with periodic boundary conditions. Activation energy for reorientational motion of CH3 group was determined from the band shape analysis of CCH3 bending vibration.

Structure-property correlation in gallic acid and 4-cyanopyridine cocrystal and binding studies with drug efflux pump in bacteria

This work focuses on the self-assembled gallic acid (GA) and 4-cyanopyridine (4-CNpy) (1:1) adduct, GA-CNpy (1), constructed from various non-covalent interactions. The cocrystal was characterized by X-ray crystallography, FT-IR and NMR spectroscopy. In the crystal lattice of 1, GA and 4-CNpy molecules are connected with each other through OH⋅⋅⋅O and NH⋅⋅⋅O hydrogen bonding interactions involving hydroxyl groups, carboxylic acid groups and 4-CNpy molecules to form a 3-D supramolecular assembly. QTAIM and NCI analyses of the optimized geometries confirm the existence of hydrogen bonds between the molecules. Further, calculations on hydrogen bonding motifs indicate that proton transfer from –OH (carboxylic acid) to N (pyridine base) is unfavorable due to high activation energy barrier. Special attention was paid to the in vitro antioxidant and antibacterial studies of 1. Our findings indicate that the GA-CNpy adduct, in its binary form, can enhance these properties to a greater extent relative to their individual counter parts. The mechanism of antibacterial activity in molecular docking study also suggests inhibitory role of the cocrystal against drug efflux pump AcrB in E. coli.

The mechanism of binding with the α-glucosidase in vitro and the evaluation on hypoglycemic effect in vivo: Cocrystals involving synergism of gallic acid and conformer

Cocrystallization of Active Pharmaceutical Ingredients (API) with formers can induce positive or negative synergistic effects on activity; however, the underlying mechanism is unclear. In this study, we screened two cocrystals of gallic acid (GA): GA-p-aminobenzoic acid (cocrystal A) and GA-amino acetic acid (cocrystal B). Solubility, dissolution rate, and oral bioavailability and hypoglycemic effect of the two cocrystals were evaluated. Additionally, we examined the effect induced by cocrystallization of GA with each former on inhibition activity on α-glucosidase, a protein target involved in hypoglycemic effects. Cocrystals A and B were constructed in a 1:1 API/former molar ratio by CO⋯HN and OH⋯OC hydrogen bonds, respectively. As predicted, cocrystallization improved oral bioavailability; AUC0-∞s of cocrystal A and B were 2.24-fold and 1.70-fold higher than that of GA. Interestingly, the α-glucosidase inhibition rate increased with cocrystal A (i.e., positive synergism) and decreased with cocrystal B (i.e., negative synergism) compared to GA alone. For each cocrystal system, an obvious difference in the α-glucosidase inhibition rate between cocrystal and its physical mixture (PM) of API and former was observed. The 1H NMR analysis of two cocrystals and their respective PM indicated that hydrogen bond interactions between API and former molecules were just present in the solutions of cocrystal; but not in that of PMs. Molecular docking indicated that the hydrogen bonds between GA and CCF achieved binding with α-glucosidase in the form of supramolecular. Due to improvements in both oral bioavailability and α-glucosidase inhibition rate, the maximum hypoglycemic rate in diabetic mice treated with cocrystal A was 3.4-fold higher than that of GA alone. Conversely, although cocrystal B displayed improved bioavailability compared with GA alone, the maximum hypoglycemic rate remained almost unchanged due to the negative synergism on α-glucosidase inhibition activity of GA and amino acetic acid. Cocrystallization with each former induced variation not only on physiochemical properties and bioavailability but also on biological profiles involving inhibition rate on target proteins, which likely contributed to the observed positive and negative synergistic effects on API activity.

Interactions between dipfluzine-based complexes and cytochrome P450 enzymes: Information on salt, cocrystal, and salt cocrystal complexes

In the new drugs, greater than 90 % of active pharmaceutical ingredients (APIs) or marketed drugs have poor solubility and bioavailability, which restrict the development of pharmaceutical preparations. The use of crystalline molecular complexes (CMCs) involving API and biocompatible precursors to improve solubility has become a shortcut for new drug development. Most of the new drugs registered in CMC form are from postmarketing drugs, and the interaction between these drugs and cytochrome P-450 (CYP) enzymes is well documented. However, it is unclear whether the interactions between CMCs of postmarketing drugs and CYP enzymes should be re-evaluated. To clarify this problem, three dipfluzine (Dip)-based CMCs, including Dip-benzoic acid (BA) cocrystal, Dip-2-hydroxybenzoate (2HB) salt and Dip-4-hydroxybenzoate (4HB) salt-cocrystal, were chosen to investigate the interaction with CYP enzymes. Metabolites of Dip-based CMCs and cocktail probe drugs were measured via LC–MS/MS in the incubation reaction system comprising recombinant CYP enzymes (rCYPs) and human liver microsomes. Dip-based CMCs not only alter Dip-mediated inhibition or activation of CYP enzymes but also change the degree to which rCYPs are involved in Dip metabolism. Specifically, the inhibitory effects of Dip and Dip-HCl were increased compared with Dip-BA and Dip-2HB for CYP1A2; Dip-BA, Dip-2HB and Dip-4HB for CYP3A4; and Dip-BA for CYP2E1. The inhibitory effects of Dip and Dip-HCl were reduced compared with Dip-2HB and Dip-4HB for CYP2C19 and Dip-4HB for CYP2E1. The effects of the alterations of Dip CMCs on the interaction between Dip and CYP enzymes are not attributed to a simple superposition of Dip and the respective precursor and may be due to the presence of interaction forces between Dip and precursor molecules. These results are the first to provide preliminary experimental evidence that CMCs change the interaction between API and CYP enzymes. Moreover, these results further suggest the importance of re-evaluating interactions with CYP enzymes when CMC strategies are used to design new drugs and even for CMCs of postmarketing drugs with known metabolic characteristics.

Cocrystallization of urea and succinic acid in “Nano-Crystallizer”

In the bulk scale of crystallization, urea-succinic acid (U-SA) cocrystals have been reported to only form stable 2:1 U-SA cocrystal, without any metastable 1:1 cocrystal, by slow evaporation and cooling crystallization in an aqueous solvent. In this work, cooling crystallization and evaporation crystallization were applied in nano-crystallizers, i.e. the nano-pores in controlled pore glass (CPG). It is the first time to demonstrate that, with confined solution, it is possible to produce and maintain metastable cocrystals during the slow crystallization process, indicating the strong influences of the confinement on the phase diagram and the thermodynamic properties of the nano-scale cocrystals. The influences of the urea and succinic acid concentration and the pore size of CPG on the polymorphs and melting point of the nanocrystal have been investigated. Further understanding of the mechanism may contribute to new methods for maintaining the unstable materials and discovering new forms of pharmaceutical compounds and materials.

Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal.

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 were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR–TER cocrystal formation was ball milling. The stoichiometry of the ITR–TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR–TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR–oxalic acid > ITR–succinic acid > ITR–TER. Additionally, the ITR–TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.

Assessment of Effects of Solvents on Cocrystallization by Computational Simulation Approach.

The sole purpose of this study is to improve the solubility and dissolution of telmisartan by cocrystallization technique and apply a computational simulation approach to assess the nature of chemical interactions between telmisartan and coformer as well as the solvent contribution to the molecules for furnishing cocrystallization. The effects of various concentrations of coformer i.e. oxalic acid on physicochemical parameters and drug release were investigated. Solubility studies suggested that cocrystallization technique with oxalic acid helps to increase the solubility of pure telmisartan of about 7 folds and drug release study revealed that telmisartan-oxalic acid cocrystals showed greater dissolution as compared to pure telmisartan. SEM study suggested that prepared telmisartan cocrystals showed rhomboid-shaped crystals with sharp edges and smooth surface. FTIR study revealed that shifting in the vibrational frequencies of C=O group of telmisartan in telmisartan- oxalic acid cocrystal indicates the formation of supra molecular hetero synthon of the cocrystal. DSC and XRD studies confirmed the formation of telmisartan-oxalic acid cocrystals. Computational simulation approach revealed that telmisartan and oxalic acid can interact with each other in the presence of methanol and water where oxalic acid can form interactions principally with the others. The interactions, thereof, may form several associations or bondings in between the drug and carrier modifying the planarity, bond energy, bond angles of both which subsequently lead to cocrystallization. So, the present research concluded that prepared telmisartan-oxalic acid cocrystal is a successful application of crystal engineering approach to improve the physicochemical properties as well as to enhance the solubility and dissolution of telmisartan.

Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal- a QbD Approach.

To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution. The carbamazepine - glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons. A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution. The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.

Polymorph and anisotropic Raman spectroscopy of Phz-H2ca cocrystals

The nucleation and growth mechanism and polymorph-property correlations in the molecular cocrystal field are widely sought but currently remain unclear. Herein, a new wire-like morphology of phenazine ( Phz )-chloranilic acid ( H2ca) cocrystal (PHC) is demonstrated for the first time, and the self-assembly of Phz and H2ca is controlled to selectively prepare kinetically stable wires and thermodynamically stable plates. Specifically, low precursor concentration is beneficial for one-dimensional (1D) self-assembly along the [010] crystallographic direction, while only supersaturation can trigger 2D self-assembly along the [100] and [010] directions, respectively. This is understandable in terms of the (020) face showing the largest attachment energy ( E att) and the (002) face possessing the smallest surface energy ( E surf). Moreover, anisotropic Raman spectra related to the mode symmetry and atomic displacements in two types of PHCs are revealed, and the same Raman-active vibrational bands of PHC wire and plate show different polarization responses, which is intrinsically ascribed to their different molecular orientations. Overall, this is the first case that morphologies of cocrystal are precisely tuned with comprehensive investigations of their anisotropic vibrational characteristics.

New curcumin-trimesic acid cocrystal and anti-invasion activity of curcumin multicomponent solids against 3D tumor models.

Curcumin (CUR) is a Biopharmaceutics Classification System (BCS) class IV drug with poor aqueous solubility and low permeability. The dissolution of CUR can be enhanced through the cocrystallization approach. In this work, we report a new cocrystal phase of CUR with trimesic acid (TMA) with the enhanced dissolution of CUR. Cytotoxicity and cell invasion assays were conducted on (2D) monolayers and three-dimensional (3D) tumor models of triple-negative breast cancer (TNBC) cells, MDA-MB-231 using the new CUR-TMA cocrystal phase along with different CUR solid forms prepared in our previous works. The cytotoxicity and internalization assays conducted on 2D monolayers indicated that all CUR multicomponent solid forms except Curcumin-Folic Acid Dihydrate (CUR-FAD) (1:1) coamorphous solid exhibited enhanced bioavailability than unprocessed CUR. Cell invasion assay conducted on 3D tumor spheroid models showed that Curcumin-Hydroxyquinol (CUR-HXQ) cocrystal completely inhibited cell invasion whereas CUR-FAD (1:1) coamorphous solid induced enhanced invasion of cells from spheroid models.

Preparation, characterization and evaluation of aspirin: benzoic acid cocrystals with enhanced pharmaceutical properties

BackgroundThe cocrystallization process in pharmaceuticals has gained widespread attention as a recent method of modifying physicochemical properties without altering the pharmacological characteristics of drugs. Cocrystallization provides a couple of benefits like it can be employed for a large number of APIs (acidic, basic, ionizable, or non-ionizable), and secondly, the availability of a large number of potential coformers increases the possibility of the cocrystals (CCs) that can be synthesized for an API. The main objective of this study was to investigate the effects of cocrystallization on drugs having poor aqueous solubility.ResultsAspirin (AN) and benzoic acid (BZ) were cocrystallized by using the solvent evaporation technique. CSD (Cambridge Structure Database) software and ∆pKa value method were used for the selection of the drug and coformer and for prediction of CC formation. The analysis of CCs was performed using DSC (differential scanning calorimetry), FT-IR (Fourier transformation infra-red spectroscopy) and XRD (X-ray diffraction) techniques. In vivo anti-inflammatory studies were conducted on 24 Wistar rats divided into four groups.ConclusionsHere, in this study, in vitro dissolution studies revealed an improved solubility profile of CCs compared to pure drug and marketed formulation viz. 87%, 31% and 60% respectively. The in vivo anti-inflammatory studies exhibited improved anti-inflammatory activity compared to pure drug. So, on the basis of outcomes of this study, we concluded that cocrystallization process have a direct impact on the improvement of physicochemical characteristics of APIs having issues like solubility or stability without any modification and alteration of their pharmacological actions.

The Role of Cocrystallization-Mediated Altered Crystallographic Properties on the Tabletability of Rivaroxaban and Malonic Acid.

The present work aims to understand the crystallographic basis of the mechanical behavior of rivaroxaban-malonic acid cocrystal (RIV-MAL Co) in comparison to its parent constituents, i.e., rivaroxaban (RIV) and malonic acid (MAL). The mechanical behavior was evaluated at the bulk level by performing “out of die” bulk compaction and at the particle level by nanoindentation. The tabletability order for the three solids was MAL < RIV < RIV-MAL Co. MAL demonstrated “lower” tabletability because of its lower plasticity, despite it having reasonably good bonding strength (BS). The absence of a slip plane and “intermediate” BS contributed to this behavior. The “intermediate” tabletability of RIV was primarily attributed to the differential surface topologies of the slip planes. The presence of a primary slip plane (0 1 1) with flat-layered topology can favor the plastic deformation of RIV, whereas the corrugated topology of secondary slip planes (1 0 2) could adversely affect the plasticity. In addition, the higher elastic recovery of RIV crystal also contributed to its tabletability. The significantly “higher” tabletability of RIV-MAL Co among the three molecular solids was the result of its higher plasticity and BS. Flat-layered topology slip across the (0 0 1) plane, the higher degree of intermolecular interactions, and the larger separation between adjacent crystallographic layers contributed to improved mechanical behavior of RIV-MAL Co. Interestingly, a particle level deformation parameter H/E (i.e., ratio of mechanical hardness H to elastic modulus E) was found to inversely correlate with a bulk level deformation parameter σ0 (i.e., tensile strength at zero porosity). The present study highlighted the role of cocrystal crystallographic properties in improving the tabletability of materials.

Understanding Matrix-Assisted Continuous Co-crystallization Using a Data Mining Approach in Quality by Design (QbD)

The present study demonstrates the application of decision tree algorithms to the cocrystallization process. 54 batches of Carbamazepine–Salicylic acid cocrystals embedded in poly(ethylene oxide) w...

Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques.

Pharmaceutical cocrystals are a promising strategy to increase the solubility and dissolution rate of poorly soluble drugs. However, their manufacturing process requires a large quantity of solvents. The present study aimed to produce cocrystals by a solvent-free hot melt extrusion (HME) method to improve their solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a weakly basic drug and acidic coformer, respectively. The processability of a plain ARP-ADP physical mixture (PM) compared with a PM with 5% Soluplus® (SOL) was investigated. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. The effects of temperature and screw speed on the formation of cocrystals were studied, and cocrystals were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy, and hot-stage microscopy. FTIR spectra revealed noncovalent interaction between ARP and ADP, which was confirmed by NMR spectra. Similarly, PXRD data exhibited characteristic peaks confirming the formation of new crystalline material. Further, the results indicated that cocrystals demonstrated higher dissolution rates and improved compressibility, as well as enhanced flow characteristics compared with pure ARP, suggesting its suitability in the development of solid dosage forms.