Conversion of viscous liquid malathion into free flowing solids through co-inclusion in urea for multiple benefits

In current investigation, malathion—a thick viscous liquid insecticide was successfully converted into free flowing solids through co-inclusion in urea for multiple benefits. Resulting fertilizer—insecticide amalgamation offer steep reduction in toxicity/odor and improved handling/formulation characteristics. Malathion (MA), a widely used organophosphate insecticide was accommodated in urea host lattice in presence of long chain rapidly complexing agent (RCA). MA is entrapped in cavities of hexagonal urea and is accordingly not accessible either to the surface/environment for inhalation or for dermal contact. Therefore, personnel engaged in handling of hazardous insecticide will not be exposed after its containment in urea lattice. Insects will be exposed to insecticide only after malathion urea co-inclusion complex (MAUCIC) comes in contact with water in soil/crops following switching on of water distribution/sprinkling system in the fields. Since, MA is engulfed in urea channels, steep reduction in petroleum like skunk odor of MA was observed. Rheological studies revealed better flow properties of MAUCIC in comparison to viscous liquid malathion. This also results in reduced cost of transportation/packaging. Minimum amount of RCA required for co-inclusion of MA in urea was determined calorimetrically. Formation of MAUCIC was characterized by FTIR, DSC, XRD and ¹H-NMR studies. Thermal studies revealed increase in heat of decomposition with corresponding increase in proportion of RCA in MAUCICs. MAUCIC complex revealed uniform formulation composition and improved dissolution profile of MA. Studies reveal fertilizer–insecticide amalgamation to be a useful technique for formulation of viscous insecticide into free flowing products with improved handling characteristics.     

Comparison of cyclodextrins and urea as hosts for inclusion of drugs

Cyclodextrins have been extensively used for inclusion of various drugs for improvement of pharmaceutical characteristics of diverse nature. Numerous derivatives of cyclodextrins are currently available and are being subjected to continuous investigations. On the other hand, urea was previously being used as host for inclusion of straight chain linear compounds. However, development of a modified technique has opened flood gates for inclusion of non-linear drugs containing cyclic moieties. Cis-retinoic acid, nicorandil, vitamin E, amiloride, glipizide, enalapril maleate, simvastatin, lafutidine and ezetimbe are some of the drugs which have already been investigated for improvement of pharmaceutical characteristics. These characteristics include improvement of stability, content uniformity, dissolution profile and rheological behavior. Recently, pesticide-fertilizer combination has also been reported to serve the dual purpose of pesticide cum fertilizer and for improvement in safe handling and formulation characteristics. All FDA approved cyclodextrins are safe chemicals for human use within permissible limits. Urea is a component of normal physiological processes of body in human beings and other mammals. Urea is far cheaper when compared to cyclodextrins. Studies reveal that despite unique characteristics of urea like high solubility, non-toxicity, stability, inexpensiveness, biodegradability and easy availability, the use of urea as a host for inclusion of drugs has been grossly overlooked by researchers. Immense potential of urea as a host for inclusion of drugs need to be explored for improvement of pharmaceutical characteristics. The relative use of both cyclodextrins and urea as hosts for inclusion of drugs has been briefly reviewed in the present article.     

Host–Guest Interaction Study of Resveratrol With Natural and Modified Cyclodextrins

The aim of this work is to increase the stability and water solubility of resveratrol by complexation with different cyclodextrins. Furthermore, physical–chemical properties of each inclusion compound were investigated. Complexes of resveratrol with cyclodextrins both native (α, β, γ) and modified (2-hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin) were obtained by using the suspension method. An inclusion complex with β-cyclodextrin was also prepared by using the microwave. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (DRX); solution studies were performed by UV–Vis spectrophotometry and ¹H-NMR spectroscopy. Phase solubility profiles with all cyclodextrins employed were classified as A_N type, indicating the formation of 1:1 stoichiometric inclusion complexes. Stability constants (K _c) from the phase solubility diagrams were calculated. Stability studies in the solid state and in solution were performed; the photodegradation by UV–Vis spectrophotometry was monitored. The isomerization rate trans to cis, in ethanol solution, decreased with inclusion. The dissolution studies revealed that resveratrol dissolution rate was improved by the formation of inclusion complexes.     

Study on the Inclusion Compounds of Eugenol with α-, β-, γ- and Heptakis (2,6-di-O-methyl)-β-cyclodextrins

Several host–guest inclusion compounds of eugenol as a guest molecule and cyclodextrins (α-,β-,γ-CD) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DMβ-CD) as hosts were investigated in the solid state and in aqueous solution. The one-to-one solid inclusion compounds of eugenol and β-CD or γ-CD were prepared, but those of eugenol with α- or DMβ-CD were not obtained under the same condition. However, the UV-visible absorption spectroscopy data indicated that the liquid guest could form a 1:1 inclusion compound with all four hosts respectively in aqueous solution. The two solid inclusion compounds were characterized by powder X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric analysis (TG), differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). The association constants (K), calculated from the modified Benesi–Hidebrand equation, of eugenol with α-, β-, γ- and DMβ-CD is 4.95 × 10⁴, 3.96 × 10⁵, 1.47 × 10⁵ and 9.33 × 10⁴ mol⁻¹ dm³, respectively.     

Enhancement of aqueous solubility of tricyclic acyclovir derivatives by their complexation with hydroxypropyl-β-cyclodextrin

Solubilities of tricyclic acyclovir derivatives in buffered aqueous solutions of hydroxypropyl-β-cyclodextrin (HP-β-CD) at pH 5.5 and 7.0 were determined at 25 and 37 °C. Complexation of these compounds with HP-β-CD resulted in a noticeable increase of their solubility; nevertheless it was limited to tricyclic derivatives of acyclovir carrying an aryl substituent. Combination of ¹H NMR and DSC techniques demonstrated the existence of inclusion complexes between acyclovir derivatives and HP-β-CD. The stability constants, estimated using the Higuchi–Connors method, were found in the range of 10–100 M⁻¹. Additionally, the pK _a values at 25 °C and molar extinction coefficients in aqueous buffered solutions were also determined for all studied compounds.     

Thermodynamic properties of nitro derivatives of diphenyl ether and biphenyl

The heat capacity of 4,4′-dinitrodiphenyl ether and 4-nitro-4′-biphenylcarboxylic acid were measured by adiabatic calorimetry (AC) in temperature ranges of 8–372 K and 10–372 K, respectively. The heat capacity of 4,4′-dinitrodiphenyl ether in the temperature range 323–500 K, the thermodynamic properties of fusion, and the purity of the ether were measured by differential scanning calorimetry (DSC). The main thermodynamic functions in the temperature range 5–370 K were calculated for both compounds using the heat capacities of adiabatic calorimetry. Related thermodynamic functions of 4,4′-dinitrodiphenyl ether in the temperature range 370–500 K were calculated on the basis of DSC data.     

Solid-state characterization and dissolution properties of ezetimibe–cyclodextrins inclusion complexes

The objectives of this research were to prepare and characterize inclusion complex of Ezetimibe (EZE) with cyclodextrins (β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HPβ-CD)) and to study the effect of complexation on the dissolution rate of EZE, a water insoluble drug. Phase solubility curve was classified as A _P -type for both cyclodextrins, indicating the 2:1 stoichiometric ratio for β-CD–EZE and HPβ-CD – EZE inclusion complexes. The inclusion complexes in the molar ratio of 2:1 (β-CD–EZE and HPβ-CD–EZE) were prepared by various methods such as kneading, coevaporation and physical mixing. The molecular behaviors of drug in all samples were characterized by fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. The results of these studies indicated that complex prepared by kneading and coevaporation methods showed inclusion of the EZE molecule into the cyclodextrins cavities. The highest improvement in in-vitro dissolution profiles was observed in complex prepared with hydroxypropyl-β-cyclodextrin using co-evaporation method. Mean dissolution time and similarity factor indicated significant difference between the release profiles of EZE from complexes and physical mixtures and from pure EZE.     

Non-isothermal kinetic study of the thermal decomposition of diaminoglyoxime and diaminofurazan

Data on the thermal stability of organic materials such as diaminofurazan (DAF) and diaminoglyoxime (DAG) was required in order to obtain safety information for handling, storage and use. These compounds have been shown to be a useful intermediate for the preparation of energetic compounds. In the present study, the thermal stability of the DAF and DAG was determined by differential scanning calorimetery (DSC) and simultaneous thermogravimetery-differential thermal analysis (TG-DTA) techniques. The results of TG analysis revealed that the main thermal degradation for the DAF and DAG occurs in the temperature ranges of 230–275°C and 180–230°C, respectively. On the other hand, the TG-DTA analysis of compounds indicates that DAF melts (at about 182°C) before it decomposes. However, the thermal decomposition of the DAG started simultaneously with its melting. The influence of the heating rate (5, 10, 15 and 20°C min⁻¹) on the DSC behaviour of the compounds was verified. The results showed that, as the heating rate was increased, decomposition temperatures of the compounds were increased. Also, the kinetic parameters such as activation energy and frequency factor for the compounds were obtained from the DSC data by non-isothermal methods proposed by ASTM E698 and Ozawa. Based on the values of activation energy obtained by ASTM and Ozawa methods, the following order in the thermal stability was noticed: DAF>DAG.     

Thermal behaviour of hydroxymethyl compounds as models for adhesive resins

Urea–formaldehyde (UF) and phenol–formaldehyde (PF) resins are the most widely used wood adhesives. The first stage in resin manufacturing is the formation of methylol derivatives which polycondensation leads to building the tridimensional network. Understanding the behaviour of methylol compounds in curing provides useful information for developing appropriate resin structures. Thermal behaviour of N,N′-dihydroxymethylurea, 2- and 4-hydroxymethylphenols, urea and phenol as model compounds for UF, PF and phenol–urea–formaldehyde (PUF) resins was followed by TG-DTA method. The measurements were carried out by the labsys instrument Setaram at 30–450 °C in nitrogen flow. The characteristic signals for model compounds and for some reaction mixtures were measured by high resolution ¹³C NMR spectroscopy.     

Phase equilibria in binary subsystems of urea–biuret–water system

Joint results of the differential scanning calorimetry (DSC) and thermogravimetry (TG) experiments were the basis for the fusion enthalpy and temperature determination of the biuret (NH₂CO)₂NH (synthesis by-product of the urea fertilizer (NH₂)₂CO). Recommended values are Δ_m H = (26.1 ± 0.5) kJ mol⁻¹, T _m = (473.8 ± 0.4) K. The DSC method allowed for the phase diagrams of “water–biuret,” “water–urea,” “urea–biuret” binary systems to be studied; as a result, liquidus and solidus curves were precisely defined. Stoichiometry and decomposition temperature of the biuret hydrate identified, composition of the compound in “urea–biuret” system was suggested.     

Determination of human urinary kanamycin in one step using urea-enhanced surface plasmon resonance light-scattering of gold nanoparticles

The purpose of this study was to establish a simple, sensitive analytical method for kanamycin (KANA) in human urine. Enhancement of the plasmon resonance light-scattering (PRLS) of gold nanoparticles (AuNPs) by KANA provided the basis for this analytical method. At pH 6.7, KANA induced AuNPs aggregation with enhanced PRLS. The PRLS of the AuNPs–KANA system was further enhanced by addition of urea. The linear range and detection limit for KANA were from 20–800 nmol L⁻¹ and 2 nmol L⁻¹, respectively. Potential interfering substances present in urine had a negligible effect on the determination, thus preliminary sample separations were not necessary. Recovery of KANA from spiked human urine was 94–104%. This simple, sensitive method, using urea to enhance the PRLS of the AuNPs–KANA system, may provide a new approach for determination of compounds rich in OH groups.     

Thermal behavior and water adsorption of natural and modified sepiolite having dolomite from Turkey

The water adsorption properties of sepiolite having dolomite supplied from Eskisehir region and their exchanged forms (K⁺, Na⁺, Mg²⁺ and Ca²⁺) were investigated. The sepiolite samples were characterized using XRD, TG-DTA, DSC and nitrogen adsorption methods. The temperature ranges were determined for the dehydrations of hydroscopic and zeolitic water as 30–200°C, for the dehydration of the bound water as 250–750°C and for the dehydroxylation of hydroxyls as 810–850°C in the sample. It was observed that the value of percent mass loss for natural and modified samples varied in the range from 36.70 to 39.05%. Two mass loss steps for all samples were observed using a differential scanning calorimetry (DSC) in the range of 30–550°C. Adsorption isotherms for water on natural and modified forms were obtained at pressures up to 2.39 kPa. Uptake of water increased as K-SEP.<Na-SEP.<Mg-SEP.<Ca-SEP. for sepiolite samples at 293 K.     

Evaluation of host-guest complex formation between a benzimidazolic derivative and cyclodextrins by UV-VIS spectrophotometry and differential scanning calorimetry

Interactions between a benzimidazolic derivative, omeprazole (OME), beta-cyclodextrin (βCD) and a chemically modified βCD, methyl-beta-cyclodextrin (MβCD) were investigated in aqueous solution by UV-VIS spectroscopy and in solid state by differential scanning calorimetry (DSC). Phase solubility studies were used to evaluate the complexation in aqueous solution. The two solubility diagrams obtained were A_L type, indicating the formation of a drug-cyclodextrin complex with 1:1 stoichiometry. The complex of OME with MβCD showed a higher stability constant (K _S) than those with βCD. Some evidences of inclusion complexation in solid state were obtained from DSC. Only in thermal curves of OME-βCD lyophilized product and in OME-MβCD spray-dried and lyophilized systems the melting point of the drug disappeared completely suggesting the possible formation of an inclusion complex.     

Synthesis of polyrotaxanes based on α-cyclodextrin and poly(ethylene oxide)

Inclusion complexes of poly(ethylene oxide) with α-cyclodextrin are the key compounds in the synthesis of polyrotaxanes. These complexes prepared in aqueous solutions contain free cyclodextrin, which cocrystallizes with the major reaction product. These complexes dissociate upon dissolution in DMF and DMSO to form cyclodextrin and pseudopolyrotaxanes with a low cyclodextrin content. Polyrotaxane was synthesized with the use of poly(ethylene oxide)-α,ω-bis-amine as a linear component. The end-groups of the polymer in the inclusion complex were modified by the reaction with 2,4-dinitrofluorobenzene. A procedure was developed for purification of a polyrotaxane with high cyclodextrin content. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1914–1918, August, 2005.     

Synthesis of Chemical Modified β-cyclodextrin and its Inclusion Behavior in Alcohol/Water Mixed Solvents

Abstract

The chemical modified β-cyclodextrin(CD), which bears a fluorophore group — N,N-dimethylamino-chalcone (DMAC), was synthesized. The self-inclusion behavior of this compound in aqueous solution and in alcohol/water mixed solvents was investigated in detail, and compared with the inclusion system of non-modified CD with free DMAC molecule. The results showed that a deep self-inclusion complex was formed for this compound in aqueous solution and had the ability to recognize different organic molecules by two fully different modes: “in-out” and “co-inclusion” mechanisms. The inclusion behavior of these systems in various ratio of alcohol/water mixture as solvents was investigated. The results indicated that the self-inclusion complex has a higher stability in alcohol/water mixed solvents than that in the case of non-modified CD. The chalcone group appended at β-CD enabled the host as a sensitive probe to study the inclusion behavior of CD.     

Synthesis,characterization and thermal behavior on solid tartrates of light trivalent lanthanides

Solid state Ln–L compounds, where Ln stands for light trivalent lanthanides (L–Gd) and L is tartrate, have been synthesized. Thermogravimetry and differential thermal analysis (TG/DTA), differential scanning calorimetry (DSC), X-ray powder diffractometry, elemental analysis and complexometry were used to characterize and to study the thermal behaviour of these compounds. The results led to information about the composition, dehydration and thermal decomposition of the isolated compounds.     

Inclusion Complexation and Dissolution Properties of Nimesulide and Meloxicam–hydroxypropyl-β-cyclodextrin Binary Systems

The purpose of the work is physicochemical characterization of nimesulide (NI) and meloxicam (ME)–hydroxypropyl-β-cyclodextrin (HP-β-CD) binary systems both in solution and solid states and to improve the pharmaceutical properties of NI and ME via inclusion complexation with HP-β-CD. Binary systems of NI and ME with HP-β-CD have been characterized both in solution and solid state by different physicochemical methods. Three types of drug–HP-β-CD binary systems, namely physical mixtures (PM), kneaded systems (KS) and co evaporated systems (CS) in 1:1 and 1:2 molar ratios (1:1 and 1:2 M) were prepared. Phase solubility and ¹H-NMR spectroscopic studies in solution state revealed 1:1 M complexation of NI and ME with HP-β-CD. A partial inclusion of NI with HP-β-CD at both molar ratios of kneaded and co evaporated systems and a true inclusion of ME with HP-β-CD at both molar ratios of co evaporated systems in solid state was confirmed by differential scanning calorimetry (DSC), powder X-ray diffractometry (powder X-RD) and scanning electron microscopy (SEM) studies. Dissolution properties of NI and ME–HP-β-CD binary systems were superior when compared to corresponding pure drugs. The aqueous solubility and dissolution properties of NI and ME can be improved by inclusion complexation with HP-β-CD. Author for correspondence: E-mail: nbnaid2@E-mail.uky.edu     

Matching Cure Characteristics of Automotive Rubber Compound and Polyurethane Coating

The present investigation focuses on matching cure characteristics of EPDM rubber compound and polyurethane (PU) coating using temperature modulated and pressure differential scanning calorimetry (TMDSC, PDSC). TMDSC provides a detailed and better understanding of the curing process of model rubber system as well as complex automotive rubber compounds. The low level of unsaturation present in EPDM, results in the small heat of vulcanization (2–5 J g^–1), which is difficult to accurately measure using conventional differential scanning calorimetry (DSC). Thus, curing of highly filled EPDM compound was investigated using TMDSC. The kinetics of PU curing was monitored using pressure DSC (PDSC), and heat of curing was determined as 4.2 J g^–1 at 10°C min^–1 heating rate. It is found that complex automotive compounds and the PU coating are curing simultaneously. This revised version was published online in July 2006 with corrections to the Cover Date.     

Spectrofluorometric, thermal, and molecular mechanics studies of the inclusion complexation of selected imidazoline-derived drugs with β-cyclodextrin in aqueous media

The inclusion complexes of selected imidazoline-derived drugs, namely Antazoline (AN), Naphazoline (NP) and Xylometazoline (XM) with β-cyclodextrin (β-CD) were investigated using steady-state fluorescence spectroscopy, differential scanning calorimetry (DSC), and molecular mechanics (MM) calculations and modeling. The modified form of the Benesi-Hildebrand relation was employed for estimating the formation constant (K_f) of the 1:1 inclusion complexes, which was applied based on measuring the variation in the fluorescence intensity of the guest molecule as a function of growing β-CD concentration. On the other hand, the formation of the inclusion complexes was verified by analyzing solid samples of the complexes using DSC. The thermodynamics of the inclusion complexation, standard enthalpy (ΔH°) and entropy changes −(ΔS°) were obtained from the temperature-dependence of K_f. Obtained values of ΔH° and ΔS° indicated that the inclusion process favorably proceeds through enthalpy changes that was sufficiently predominant to compensate for the unfavorable entropy changes. MM calculations revealed that the proposed drugs molecules can form 1:1 inclusion complexes with β-CD that are stabilized predominantly through van der Waals forces. In addition, MM calculation provided the energetically favored configuration of the inclusion complexes, where NP and XM can be included inside the β-CD cavity through its wide rim, whereas AN can penetrate through the narrow rim of the β-CD cavity.     

Sulphamethizole-Cyclodextrin-Hydroxy Propylmethyl Cellulose Multicomponent Complexes

The effect of cyclodextrin complexation of sulphamethizole (SM) was studied. Two systems were prepared with two cyclodextrin derivatives, β-cyclodextrin (BCD) and hydroxypropyl-β-cyclodextrin (HPBCD): binary complexes and multicomponent systems (cyclodextrins and a hydroxylpropylmethyl cellulose K4M). Inclusion complexes were prepared by freeze-drying and characterized by thermal analysis (DSC) and X-ray diffractometry. The presence of the polymer in the solution increases the effect of cyclodextrins – specially BCD – on the solubility of SM. In solid state, binary inclusion complexes enhance the dissolution behaviour of SM but, from the multi-component complexes, the polymer controls the release of the drug. This revised version was published online in August 2006 with corrections to the Cover Date.