Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins.

Riluzole (RLZ), a sodium channel-blocking benzothiazole anticonvulsant BCS class II drug, is very slightly soluble in aqueous medium. To improve aqueous solubility and modulate dissolution rate and membrane permeability, complex formation of RLZ with two cyclodextrin, α-cyclodextrin (α-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD), was studied. The stability constants demonstrated a greater affinity of SBE-β-CD towards RLZ compared to α-CD.

Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine.

The present study reports the effects of two pharmaceutical excipients of differing natures-non-ionic surfactant pluronic F127 (F127) and anionic sulfobutylether-β-cyclodextrin (SBE-β-CD)-on the permeation of the model compound, carbamazepine (CBZ). The permeability coefficients of CBZ at three concentrations of the excipients were measured through two different artificial barriers: hydrophilic cellulose membrane (RC) and lipophilic polydimethylsiloxane-polycarbonate membrane (PDS). The equilibrium solubility of CBZ in F127 and SBE-β-CD solutions was determined.

Correction: Volkova et al. Cyclodextrin's Effect on Permeability and Partition of Nortriptyline Hydrochloride. 2023, , 1022.

In the original publication [...

Cyclodextrin's Effect on Permeability and Partition of Nortriptyline Hydrochloride.

Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-β-CD and SBE-β-CD on the distribution and permeability of nortriptyline hydrochloride (NTT•HCl), a tricyclic antidepressant drug. To this end, the distribution coefficients in the 1-octanol/buffer and n-hexane/buffer model systems and the coefficients of permeability through the cellulose membrane and lipophilic PermeaPad barrier were determined at several cyclodextrin concentrations.

Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance.

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 of the solid forms revealed a close resemblance between novel form II and previously reported form I of the [CBZ + MePRB] (1:1) cocrystal in terms of hydrogen bond networks and overall packing arrangements.

Modulation of Distribution and Diffusion through the Lipophilic Membrane with Cyclodextrins Exemplified by a Model Pyridinecarboxamide Derivative.

The main aims of the study were to disclose the influence of the structure on the solubility, distribution and permeability of the parent substances, iproniazid (IPN), isoniazid (INZ) and isonicotinamide (iNCT), at 310.2 K and to evaluate how the presence of cyclodextrins (2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and methylated β-cyclodextrin (M-β-CD)) affects the distribution behavior and diffusion properties of a model pyridinecarboxamide derivative, iproniazid (IPN). The following order of decreasing the distribution and permeability coefficients was estimated: IPN > INZ > iNAM.

Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals.

In this study, the existing set of carbamazepine (CBZ) cocrystals was extended through the successful combination of the drug with the positional isomers of acetamidobenzoic acid. The structural and energetic features of the CBZ cocrystals with 3- and 4-acetamidobenzoic acids were elucidated via single-crystal X-ray diffraction followed by QTAIMC analysis. The ability of three fundamentally different virtual screening methods to predict the correct cocrystallization outcome for CBZ was assessed based on the new experimental results obtained in this study and data available in the literature.

Revisiting the Solubility-Permeability Relationship with Hydrophobic Drug Umifenovir in Pluronic Solutions: Impact of pH and Co-Solvent.

This study describes the influence of pluronic F-127 (F-127) and ethanol (EtOH) on the solubility of umifenovir (UMF) in buffer solutions of pH 2.0 and pH 7.4, and its permeability through cellulose membranes.

Influence of Co-amorphization on the Physical Stability and Dissolution Performance of an Anthelmintic Drug Flubendazole.

In this work, the co-amorphization approach was applied to flubendazole (FluBZ), resulting in the formation of two novel solid forms of FluBZ with l-phenylalanine (Phe) and l-tryptophan (Trp). A variety of physicochemical techniques have been used to describe new systems, including powder X-ray diffraction, thermal methods, infrared spectroscopy, and scanning electron microscopy. Co-amorphization has been shown to suppress crystallization tendency and considerably increase the shelf-life storage of amorphous flubendazole solid across a wide range of relative humidities.

Permeability of New Antifungal Fluconazole Derivatives through a Lipophilic Membrane: Experiment and Modeling.

Relationships between the structures of molecules and their properties form the basis of modern chemistry and lay the foundation for structure-based drug design. Being the main two determinants of bioavailability, solubility and permeability of drugs are widely investigated experimentally and predicted from physicochemical parameters and structural descriptors. In the present study, we measure the passive diffusion permeability of a series of new fluconazole derivatives with triazole and thiazolo-pyrimidine moieties connected by different linker bridges through the PermeaPad barrier-a relatively new biomimetic lipophilic membrane that has been increasingly used in recent years.

New Solid Forms of Nitrofurantoin and 4-Aminopyridine Salt: Influence of Salt Hydration Level on Crystal Packing and Physicochemical Properties.

The crystallization of the poorly soluble drug nitrofurantoin (NFT) with 4-aminopyridine (4AmPy) resulted in three multicomponent solid forms with different hydration levels: anhydrous salt [NFT+4AmPy] (1:1), salt monohydrate [NFT+4AmPy+HO] (1:1:1), and salt tetrahydrate [NFT+4AmPy+HO] (1:1:4). Each salt was selectively prepared by liquid-assisted grinding in the presence of acetonitrile or ethanol/water mixture at a specific composition. The NFT hydrated salts were characterized using single crystal X-ray diffraction.

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds.

The important physicochemical properties of three novel bioactive hybrid compounds with different groups (-CH, -F and -Cl) were studied, including kinetic and thermodynamic solubility in pharmaceutically relevant solvents (buffer solutions and 1-octanol) as well as partition coefficient in system 1-octanol/buffer pH 7.4. The aqueous solubility of these chemicals is poor and ranged from 0.

Formation Thermodynamics of Carbamazepine with Benzamide, Para-Hydroxybenzamide and Isonicotinamide Cocrystals: Experimental and Theoretical Study.

Formation thermodynamic parameters for three cocrystals of carbamazepine (CBZ) with structurally related coformers (benzamide (BZA), para-hydroxybenzamide (4-OH-BZA) and isonicotinamide (INAM)) were determined by experimental (cocrystal solubility and competitive reaction methods) and computational techniques. The experimental solubility values of cocrystal components at eutectic points and solubility product of cocrystals [CBZ + BZA], [CBZ + 4-OH-BZA], and [CBZ + INAM] in acetonitrile at 293.15 K, 298.

Synthesis, Neuroprotective Effect and Physicochemical Studies of Novel Peptide and Nootropic Analogues of Alzheimer Disease Drug.

Glutamate is an excitatory neurotransmitter in the nervous system. Excessive glutamate transmission can lead to increased calcium ion expression, related to increased neurotoxicity. Memantine is used for treating patients with Alzheimer's disease (AD) due to its protective action on the neurons against toxicity caused by over activation of N-methyl-D-aspartate receptors.

Another Move towards Bicalutamide Dissolution and Permeability Improvement with Acetylated β-Cyclodextrin Solid Dispersion.

The complex formation of antiandrogen bicalutamide (BCL) with methylated (Me-β-CD) and acetylated (Ac-β-CD) β-cyclodextrins was investigated in buffer solution pH 6.8. A two-fold strongly binding of BCL to Ac-β-CD as compared to Me-β-CD was revealed.

Simultaneous Improvement of Dissolution Behavior and Oral Bioavailability of Antifungal Miconazole via Cocrystal and Salt Formation.

Miconazole shows low oral bioavailability in humans due to poor aqueous solubility, although it has demonstrated various pharmacological activities such as antifungal, anti-tubercular and anti-tumor effects. Cocrystal/salt formation is one of the effective methods for solving this problem. In this study, different methods (liquid-assisted grinding, slurrying and lyophilization) were used to investigate their impact on the formation of the miconazole multicomponent crystals with succinic, maleic and dl-tartaric acids.

Chiral Recognition R- and RS- of New Antifungal: Complexation/Solubilization/Dissolution Thermodynamics and Permeability Assay.

Novel potential antifungal of 1,2,4-triazole class have been synthesized as pure enantiomer (R-98) and racemic (RS-186). The effect of 2-hydroxypropyl-β-cyclodextrin () on the solubility and permeability of RS-186 and R-98 in terms of chiral recognition was investigated. Phase solubility studies were carried out at 4 temperatures in 0-0.

Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability.

The pharmacologically relevant physicochemical properties of the antiandrogen drug bicalutamide (BCL) have been determined for the first time. Solubility in aqueous solution, 1-octanol, n-hexane, and ethanol was measured by the shake flask method in the temperature range of 293.15−313.

New Antifungal Compound: Impact of Cosolvency, Micellization and Complexation on Solubility and Permeability Processes.

Poor solubility of new antifungal of 1,2,4-triazole class (S-119)-a structural analogue of fluconazole in aqueous media was estimated. The solubility improvement using different excipients: biopolymers (PEGs, PVP), surfactants (Brij S20, pluronic F-127) and cyclodextrins (α-CD, β-CD, 2-HP-β-CD, 6-O-Maltosyl-β-CD) was assessed in buffer solutions pH 2.0 and pH 7.

Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media.

A temperature dependence of saturated vapor pressure of isavuconazole (IVZ), an antimycotic drug, was found by using the method of inert gas-carrier transfer and the thermodynamic functions of sublimation were calculated at a temperature of 298.15 K. The value of the compound standard molar enthalpy of sublimation was found to be 138.

A Combined Experimental and Theoretical Study of Nitrofuran Antibiotics: Crystal Structures, DFT Computations, Sublimation and Solution Thermodynamics.

Single crystal of furazolidone (FZL) has been successfully obtained, and its crystal structure has been determined. Common and distinctive features of furazolidone and nitrofurantoin (NFT) crystal packing have been discussed. Combined use of QTAIMC and Hirshfeld surface analysis allowed characterizing the non-covalent interactions in both crystals.

Polymorphic forms of antiandrogenic drug nilutamide: structural and thermodynamic aspects.

Attempts to obtain new cocrystals of nonsteroidal antiandrogenic drug nilutamide produced alternative polymorphic forms of the compound (Form II and Form III) and their crystal structures were elucidated by single-crystal X-ray diffraction. Apart from the cocrystallization technique, lyophilization was found to be an effective strategy for achieving polymorph control of nilutamide, which was difficult to obtain by other methods. The physicochemical properties and relative stability of the commercial Form I and newly obtained Form II were comprehensively investigated by a variety of analytical methods (thermal analysis, solution calorimetry, solubility, and sublimation), whereas for Form III, only a handful of experimental parameters were obtained due to the elusive nature of the polymorph.

Synthesis and antifungal activity of new hybrids thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazole.

Synthesis and antifungal activity of hybrids of thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazoles are presented. The solubility and lipophilicity of compounds was assessed and it was discovered that compounds with piperazine linker exhibited significant antifungal activity against filamentous and yeast fungi.

Novel cocrystals of itraconazole: Insights from phase diagrams, formation thermodynamics and solubility.

In this work, the cocrystallization approach was applied to itraconazole (ITR), a very slightly soluble triazole antifungal drug, which led to the formation of two new solid forms of ITR with 4-aminobenzoic acid (4AmBA) and 4-hydroxybenzamide (4OHBZA). A thermodynamic analysis of the solid-liquid binary phase diagrams for the (ITR + 4AmBA) and (ITR + 4OHBZA) systems provided conclusive evidence of the cocrystal stoichiometry: 1:1 for the cocrystal with 4-aminobenzoic acid, and 1:2 for the cocrystal with 4-hydroxybenzamide. Powder X-Ray diffraction analysis confirmed the formation of two different polymorphic forms of the [ITR + 4OHBZA] (1:2) cocrystal obtained either through solution or melt crystallization.

Synthetic analogues of memantine as neuroprotective and influenza viral inhibitors: in vitro and physicochemical studies.

Drug compounds including memantine moieties are an important group of biologically active agents for different pathologies, including the Alzheimer's disease. In the present study, a series of memantine derivatives incorporating amino acid residues have been synthesized and their neuroprotective in vitro evaluation in respect of the Alzheimer's disease, involving the effects on the resistance to Aβ toxicity, excitotoxicity, oxidative stress, hypoxia, and neuroinflammation has been studied. The cytotoxicities of the compounds were detected by CPE assay.