γ-Cyclodextrin nanoparticle eye drops with dorzolamide: effect on intraocular pressure in man.

Purpose: To test a new drug delivery platform with dorzolamide γ-cyclodextrin (γCD) nanoparticle eye drops for intraocular pressure (IOP) control and safety and compare with Trusopt.(®)

Methods: Self-aggregating γCD nanoparticle eye drops containing 3% dorzolamide were given once a day (QD) and compared with Trusopt given three times a day (TID) in a prospective randomized single masked crossover trial over 24 h. Seventeen subjects with IOP over 18 mmHg were recruited.

Cationic quaternized aminocalix[4]arenes: cytotoxicity, haemolytic and antibacterial activities.

This study reports the characterization of three cationic amphiphillic aminocalix[4]arenes as potential antimicrobial agents in vitro. In cytotoxicity tests on mouse macrophage RAW 264.7 cells aminocalix[4]arenes 1 and 3 showed no toxicity up to 200 and 100 μM concentrations, respectively, while 2 was non-toxic only up to 50 μM.

Encapsulation of drug molecules into calix[n]arene nanobaskets. role of aminocalix[n]arenes in biopharmaceutical field.

Calix[n]arenes (CAs) are supramolecular compounds able to form guest-host inclusion complexes with metal ions, small organic molecules, and small moieties of larger molecules. Although the CA literature is extensive, relatively few publications deal with water-soluble CAs, especially those containing nitrogen-based functionality. These CAs possess antibacterial and antifungal activity.

The effect of parenterally administered cyclodextrins on the pharmacokinetics of coadministered drugs.

Cyclodextrins are used increasingly to formulate otherwise poorly soluble molecules for clinical use. Cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether β-cyclodextrin (SBEβCD), are found in marketed parenteral drug formulations. Depending upon the relative affinities of a coadministered medication for cyclodextrin and plasma proteins, complexation with HPβCD or SBEβCD may alter its pharmacokinetics (PK).

Cyclodextrins.

Although cyclodextrins (CDs) have been studied for over 100 years and can be found in at least 35 pharmaceutical products, they are still regarded as novel pharmaceutical excipients. CDs are oligosaccharides that possess biological properties that are similar to their linear counterparts, but some of their physicochemical properties differ. CDs are able to form water-soluble inclusion complexes with many poorly soluble lipophilic drugs.

Self-assembly of cyclodextrin complexes: effect of temperature, agitation and media composition on aggregation.

Recently it has been shown that aggregation of drug/cyclodextrin inclusion complexes is strongly influenced by the drug molecule in addition to self-assembling tendencies of the cyclodextrin itself in aqueous media. Whereas the mechanistic basis of cyclodextrin self-assembly is known, the driving forces for complex aggregation are still unknown. In the present study, the influence of temperature on hydrocortisone/2-hydroxypropyl-β-cyclodextrin complex aggregation is investigated as are influences associated with the addition of ethanol or water soluble polymers to the aqueous systems.

Evaluation of sugammadex self-association.

Sugammadex, a thiolated γCD derivative used as an antagonist of steroidal blockers, was studied with regard to its tendency to self-associate in aqueous solution. Three independent methods - permeation through semi-permeable cellophane membranes, dynamic light scattering, and sedimentation equilibrium analytical ultracentrifugation - were used for this purpose. The results were in agreement with each other and showed no evidence of self-association in a wide sugammadex concentration range from 0.

Self-assembly of cyclodextrins: the effect of the guest molecule.

The principle action by which cyclodextrins solubilize compounds is via inclusion complex formation. However, data suggest that cyclodextrins and their complexes also aggregate in solution and this aggregation contributes to their ability to solubilize poorly water-soluble materials. The current effort aims at better understanding the role of guest molecule nature (i.

Self-assembly of cyclodextrin complexes: aggregation of hydrocortisone/cyclodextrin complexes.

Cyclodextrins (CDs) are well known functional excipients for solubilization and stabilization of drugs in aqueous formulations as well as enabling adjuncts for increasing the oral bioavailability of solid dosage forms. More recently a number of the valuable properties of these CDs have been ascribed to nanoparticulate aggregation in addition to its ability to form molecular inclusion complexes. The purpose of this study is to identify and characterize the aggregation of CD inclusion complexes with a model drug, hydrocortisone, in saturated solutions which are more relevant to drug formulation than highly dilute systems.

Evaluation of a cationic calix[4]arene: Solubilization and self-aggregation ability.

Water-soluble calixarenes are promising macrocyclic compounds which have found numerous applications in chemistry and biology. However, these compounds have been less studied in regard to their behavior in aqueous solutions and mechanisms of drug solubilization. The present work is devoted to the evaluation of the solubilizing properties and estimation of self-aggregation ability of positively charged 5,11,17,23-tetrakis(trimethylammoniomethyl)-25,26,27,28-tetrapropoxy-calix[4]arene tetrachloride (aminocalix), including comparisons with a series of pharmaceutically relevant cyclodextrins.

Parenteral delivery of HPβCD: effects on drug-HSA binding.

It is thought that cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin (HPβCD), will at high concentration affect pharmacokinetics of drugs through competitive binding with plasma proteins. Albumin is the major component of plasma proteins responsible for plasma protein binding. The purpose of this study was to evaluate in vitro the competitive binding of drugs between human serum albumin (HSA) and HPβCD in isotonic pH 7.

Self-assembled cyclodextrin aggregates and nanoparticles.

Cyclodextrins (CDs) are widely used as enabling pharmaceutical excipients, mainly as solubilizing complexing agents. CDs are cyclic oligosaccharides with hydrophilic outer surface and a somewhat lipophilic central cavity. In aqueous solutions CDs are able to solubilize lipophilic drugs by taking up some lipophilic moiety of the drug molecule into the central cavity, i.

Cyclodextrins as solubilizers: formation of complex aggregates.

Three different techniques were applied to investigate aggregation of drug/cyclodextrin complexes, that is, drug permeation through semi-permeable membranes, determination of changes in the value of activity coefficients of drug/cyclodextrin complex solutions and transmission electron microscopy (TEM). The aqueous solutions studied contained gamma-cyclodextrin, 2-hydroxypropyl-gamma-cyclodextrin or mixtures thereof, and hydrocortisone, amphotericin B, diclofenac sodium or indomethacin. The permeation studies indicated that drug/cyclodextrin complex monomers (i.

Novel isothiourea derivatives as potent neuroprotectors and cognition enhancers: synthesis, biological and physicochemical properties.

Various salts of 3-allyl-1,1-dibenzyl-2-ethyl-isothiourea, 1 (hydrochloride), 2 (hydrobromide), and 3 (hydroiodide), were synthesized. Ca-blocking properties of these salts were studied. Comparative analysis of the potentiating effects of 3 and cyclothiazide (CT) on transmembrane currents caused by kainic acid (KA) and glutamate in Purkinje neurons was performed.

Thermodynamic studies of Fenbufen, Diflunisal, and Flurbiprofen: sublimation, solution and solvation of biphenyl substituted drugs.

Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP) were measured, and standard thermodynamic functions of sublimation were calculated (FBF: DeltaGsub298=74.0 kJ mol(-1); DeltaHsub298=155.

The difference between partitioning and distribution from a thermodynamic point of view: NSAIDs as an example.

Solubility and solvation of some NSAIDs were studied in their non-ionic (aqueous buffers of pH 2.0) and ionic molecular form (pH 7.4) over a wide temperature interval.

Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid.

Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, DeltaH(0) (sub), as well as the entropies of sublimation, DeltaS(0) (sub), and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen).

Thermodynamics of solutions III: comparison of the solvation of (+)-naproxen with other NSAIDs.

Naproxen was studied by classical thermoanalytical methods, namely sublimation calorimetry, solution calorimetry and the solubility method. Temperature dependence of a saturated vapor pressure was obtained and the sublimation enthalpy, deltaHsub(0) and entropy, deltaSsub(0) and their relative fraction of the total process were calculated. These parameters yielded for naproxen were compared to the respective data of other naphthalene derivatives.

Thermodynamics of sublimation, crystal lattice energies, and crystal structures of racemates and enantiomers: (+)- and (+/-)-ibuprofen.

Thermodynamic differences between ibuprofen (IBP) racemate and the (+)-enantiomer were studied by X-ray diffraction, thermoanalysis, and crystal energy calculations. The thermodynamic functions of sublimation (as a measure of crystal lattice energy) were obtained by the transpiration method. The sublimation enthalpies (DeltaH(sub)) of (+/-)-IBP and (+)-IBP are 115.

Thermodynamics of solutions IV: Solvation of ketoprofen in comparison with other NSAIDs.

The present work discusses the characteristics of solvation (Gibbs energy, enthalpic and entropic terms of Gibbs energy) for ketoprofen together with other nonsteroidal antiinflammatory drugs (NSAIDs) in aliphatic alcohols. Ketoprofen was studied by classical thermoanalytical methods of sublimation calorimetry, solution calorimetry, and solubility. Temperature dependence of the saturated vapor pressure was determined, and the sublimation enthalpy, delta H(sub) (0) and sublimation entropy, delta S(sub)(0), as well as their respective relative fractions in the total process were calculated.

Thermodynamics of solutions. II. Flurbiprofen and diflunisal as models for studying solvation of drug substances.

Three independent methods (sublimation, solubility and solution calorimetry) were used to study the dissolution and solvation processes of diflunisal (DIF) and flurbiprofen (FBP). Thermodynamic functions for the sublimation of DIF and FBP were obtained. Concentrations of saturated solutions and standard solution enthalpies of DIF and FBP in aliphatic alcohols and individual organic solvents were measured.