Apparent Water Solubility Research Articles

Cyclodextrin-based nanocarriers containing a synergic drug combination: A potential formulation for pulmonary administration of antitubercular drugs

Tuberculosis (TB) remains a major global health problem. The use of ethionamide (ETH), a main second line drug, is associated to severe toxic side-effects due to its low therapeutic index. In this challenging context, “booster” molecules have been synthetized to increase the efficacy of ETH. However, the administration of ETH/booster pair is mostly hampered by the low solubility of these drugs and the tendency of ETH to crystallize. Here, ETH and a poorly water-soluble booster, so-called BDM43266, were simultaneously loaded in polymeric β-cyclodextrin nanoparticles (pβCyD NPs) following a “green” protocol. The interaction of ETH and BDM43266 with pβCyD NPs was investigated by complementary techniques. Remarkably, the inclusion of ETH and BDM43266 pβCyD NPs led to an increase of their apparent solubility in water of 10- and 90-fold, respectively. Competition studies of ETH and BDM43266 for the CyD cavities of pβCyD NPs corroborated the fact that the drugs did not compete with each other, confirming the possibility to simultaneously co-incorporate them in NPs. The drug-loaded NP suspensions could be filtered through 0.22μm filters. Finally, the drug-loaded NPs were passed through a Microsprayer® to evaluate the feasibility to administer pβCyD NPs by pulmonary route. Each spray delivered a constant amount of both drugs and the NPs were totally recovered after passage through the Microsprayer®. These promising results pave the way for a future use of pβCyD NPs for the pulmonary delivery of the ETH/BDM43266 pair.

Dermal quercetin lipid nanocapsules: Influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide

Quercetin is a plant flavonoid with strong antioxidant and antiinflammatory properties interesting for skin protection. However, its poor water solubility limits its penetration and so its efficiency on skin. For this purpose, quercetin lipid nanocapsules were formulated implementing phase inversion technique wherein several modifications were introduced to enhance quercetin loading. Quercetin lipid nanocapsules were formulated with two particle size range, (50nm and 20nm) allowing a drug loading of 18.6 and 32mM respectively. The successful encapsulation of quercetin within lipid nanocapsules increased its apparent water solubility by more than 5000 fold (from 0.5μg/ml to about 5mg/ml). The physicochemical properties of these formulations such as surface charge, stability and morphology were characterized. Lipid nanocapsules had spherical shape and were stable for 28days at 25°C. Quercetin release from lipid nanocapsules was studied and revealed a prolonged release kinetics during 24h. Using DPPH assay, we demonstrated that the formulation process of lipid nanocapsules did not modify the antioxidant activity of quercetin in vitro (92.3%). With the goal of a future dermal application, quercetin lipid nanocapsules were applied to THP-1 monocytes and proved the cellular safety of the formulation up to 2μg/ml of quercetin. Finally, formulated quercetin was as efficient as the crude form in the protection of THP-1 cells from oxidative stress by exogenous hydrogen peroxide. With its lipophilic nature and occlusive effect on skin, lipid nanocapsules present a promising strategy to deliver quercetin to skin tissue and can be of value for other poorly water soluble drug candidates.

Hot foam for weed control—Do alkyl polyglucoside surfactants used as foaming agents affect the mobility of organic contaminants in soil?

Use of alkyl polyglucosides (APGs) as a foaming agent during hot water weed control may influence the environmental fate of organic contaminants in soil. We studied the effects of the APG-based foaming agent NCC Spuma (C8-C10) on leaching of diuron, glyphosate, and polycyclic aromatic hydrocarbons (PAHs) in sand columns. We also examined how APG concentration affected the apparent water solubility and adsorption of the herbicides and of the PAHs acenaphthene, acenaphthylene and fluorene. Application of APGs at the recommended concentration of 0.3% did not significantly affect leaching of any of the compounds studied. However, at a concentration of 1.5%, leaching of both diuron and glyphosate was significantly increased. The increased leaching corresponded to an increase in apparent water solubility of diuron and a decrease in glyphosate adsorption to the sand. However, APG addition did not significantly affect the mobility of PAHs even though their apparent water solubility was increased. These results suggest that application of APG-based foam during hot water weed control does not significantly affect the mobility of organic contaminants in soil if used according to recommendations. Moreover, they suggest that APGs could be useful for soil bioremediation purposes if higher concentrations are used.

Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis®, however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis® are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization.

사출구 온도와 반복 압출성형이 백삼압출성형물의 물리적 특성에 미치는 영향

ABSTRACT The aim of this study was to investigate the effect of die temperature and repeated extrusion on physical properties of extruded white ginseng (EWG). The die temperature was adjusted to 100, 120, and 140°C, and extrusion was repeated under the same conditions with their corresponding samples. Specific mechanical energy input decreased as die temperature increased during extrusions. The secondary extruded white ginseng (SEWG) at a die temperature of 120°C showed a higher expansion index than other extrudates. Elevation of both die temperature and repeated extrusion increased the specific length of extrudates. The highest apparent elastic modulus, breaking strength, and water solubility index obtained from SEWG at a die temperature of 100°C were 7.53×10 8 N/m 2 , 7.49×10 5 N/m 2 , and 39.02%, respectively. When die temperature increased, water absorption index (WAI) decreased. The WAI of SEWG was higher than that of EWG. In conclusion, repeated extrusion affected physical properties of white ginseng and could be applied to produce improved quality of ginseng products.

The unexpected increase of clotrimazole apparent solubility using randomly methylated β-cyclodextrin.

Clotrimazole (CTZ) and cyclodextrin (CD) inclusion complexes having improved apparent water solubility were obtained from phase solubility diagrams. β-CD (1.5% w/w) and hydroxypropyl-β-CD (40% w/w) offered poor CTZ solubility enhancements (12 and 384 times, respectively). Unexpectedly, the apparent solubility of CTZ was 9980 times increased from 0.4 µg.mL(-1) (1.42 μM) without CD to 4.89 mg.mL(-1) (14.9 mM) using randomly-methylated β-CD (Me-β-CD) (40% w/w). This is the highest apparent CTZ solubility improvement ever reported in the literature using conventional CDs. Quantitative nuclear magnetic resonance ((1) H-NMR) coupled with two-dimensional nuclear Overhauser effect (NOESY) experiments and molecular docking calculations showed that the highest interactions with Me-β-CD were reported for CTZ two phenyl groups. A lower interaction was reported for chlorophenyl, while imidazole had the weakest interaction with Me-β-CD.

Enhanced antibacterial and anti-quorum sensing activities of triclosan by complexation with modified β-cyclodextrins

Triclosan (TCS), an antimicrobial agent widely used in consumer and medical products, was complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD). Phase-solubility studies indicated that inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of the associated equilibrium constants and free-energy changes. At the highest cyclodextrin concentrations investigated, an almost 20-fold increase in the apparent water solubility of TCS was determined. Susceptibility tests against Escherichia coli and Staphylococcus aureus showed that the TCS-HPβCD and TCS-MβCD complexes exhibited antibacterial properties higher than those of uncomplexed TCS. The two complexes were also found capable of interfering with cell-to-cell communication mechanisms in the C. violaceum model system relying on N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased significantly upon inclusion of the drug in HPβCD or MβCD, with small differences between the two CDs. The results obtained suggest that the investigated complexes could be used for treating infections caused by TCS-susceptible pathogens or for preventing biofilm formation on indwelling medical devices such as catheters, stents and orthopedic implants.

EDDS-enhanced electrokinetic remediation of heavy metal-contaminated clay soils under neutral pH conditions

Electrokinetic remediation of heavy metal-contaminated clay soils under neutral pH conditions is a challenging task due to the low water solubility of heavy metals. The objective of this study was to apply a biodegradable [S,S]-ethylenediamine disuccinic acid ([S,S]-EDDS) chelating agent to clay soils under neutral pH conditions to enhance the electrokinetic remediation efficiencies of cadmium (Cd) and lead (Pb). Bench-scale laboratory experiments were designed to investigate the influence of the [S,S]-EDDS concentration, applied voltage, and electrode materials on the remediation efficiencies. The soil pH was maintained near 7.0 for all of the experiments by adding HNO3 or NaOH in the electrode solutions. The experimental results showed that lead was not effectively removed from clay soils without the presence of [S,S]-EDDS due to its poor water solubility at neutral pH conditions. The remediation efficiencies were significantly enhanced by adding [S,S]-EDDS, indicating that the formation of the Pb–EDDS complexes increased the apparent water solubility of lead. The lead remediation efficiencies were enhanced by increasing either the applied voltage or the [S,S]-EDDS concentration. It was also determined that the electrode materials significantly influenced the remediation efficiency in the following order: platinum-coated titanium>iridium dioxide-coated titanium>graphite. Conversely, in case of cadmium, which has higher water solubility than lead, negatively charged Cd–EDDS complexes and positively charged cadmium ions moved in opposing directions, and as a result, cadmium accumulated at the center of the soil column. This study provided fundamental information on the design of an electrokinetic remediation system and will be useful to optimize the remediation conditions.

Enhanced Solubilisation of Six PAHs by Three Synthetic Cyclodextrins for Remediation Applications: Molecular Modelling of the Inclusion Complexes

Solubilisation of six polycyclic aromatic hydrocarbons (PAHs) (acenaphthene, anthracene, fluoranthene, fluorene, phenanthrene and pyrene) by three synthetic cyclodextrins (CDs) (2-hydroxypropyl-β-CD, hydroxypropyl-γ-CD and ramdomly methylated-β-CD) was investigated in order to select the CD which presents the greatest increase in solubility and better complexation parameters for its use in contaminated scenarios. The presence of the three cyclodextrins greatly enhanced the apparent water solubility of all the PAHs through the formation of inclusion complexes of 1∶1 stoichiometry. Anthracene, fluoranthene, fluorene and phenanthrene clearly presented a higher solubility when β-CD derivatives were used, and especially the complexes with the ramdomly methylated-β-CD were favoured. On the contrary, pyrene presented its best solubility results when using 2-hydroxypropyl-γ-CD, but for acenaphthene the use of any of the three CDs gave the same results. Complementary to experimental phase-solubility studies, a more in-depth estimation of the inclusion process for the different complexes was carried out using molecular modelling in order to find a correlation between the degree of solubilisation and the fit of PAH molecules within the cavity of the different CDs and to know the predominant driving forces of the complexation.

Improvement of Water Solubility of Josamycin by Inclusion Complex with -Cyclodextrin

Josamycin propionate (JMP) is an antibiotic belonging to the family of macrolide. According to the Biopharmaceutical Classification System (BCS), this compound can be classed in class II, low solubility and high permeability. In order to increase its apparent water solubility, inclusion complexation between Josamycin propionate and γ-cyclodextrin (γ-CD) was studied. UV spectrophotometric method was employed to investigate the phase-solubility profile and the stability constant of the complexation in aqueous medium. Solid state of the binary system prepared by coevaporation (in 50%-50% ethanol/water) has been characterized using powder X-ray diffraction (XRD) and Fourier transformation-infrared spectrometry (FTIR). These techniques indicate that JMP forms an association complex with γ-CD. The shift in the nuclear magnetic resonance spectroscopy (1H NMR) confirms the existence of the inclusion complex. Also the results obtained showed an enhancement of the solubility in water of Josamycin propionate.

Bivalent sequential binding of docetaxel to methyl-β-cyclodextrin

New docetaxel (Dtx) and cyclodextrin (CD) inclusion complexes having improved apparent water solubility (up to 9.98 mg mL −1) were obtained from phase solubility diagrams. γ-CD and SBE-β-CD offered only poor solubility enhancements while considerable increases in apparent solubility were obtained with Me-β-CD (20%, w/w) and HP-β-CD (40%, w/w) (9.98 mg mL −1 and 7.43 mg mL −1, respectively). The complexation mechanism between Dtx and Me-β-CD was investigated by circular dichroism spectrometry, two-dimensional 1H NMR (NOESY) in D 2O, isothermal titration calorimetry (ITC) and molecular docking calculations. Circular dichroism and NOESY confirmed the existence of non-covalent interactions between Dtx and Me-β-CD and suggested that the tert-butyl group (C 6–C 9) and two aromatic groups (C 24–C 29 and C 30–C 35) of Dtx interacted with the Me-β-CD molecules. The combination of ITC results to molecular docking calculations led to the identification of an unconventional sequential binding mechanism between Me-β-CD and Dtx. In this sequential binding, a Me-β-CD molecule first interacted with both tert-butyl and C 30–C 35 aromatic groups ( K 1: 744 M −1). Then a second Me-β-CD molecule interacted with the C 24–C 29 aromatic group ( K 2: 202 M −1). The entropy of the first interaction was positive, whereas a negative value of entropy was found for the second interaction. The opposite behavior observed for these two sites was explained by differences in the hydrophobic contact surface and functional group flexibility.

C 60-DOM interactions and effects on C 60 apparent solubility: A molecular mechanics and density functional theory study

Dissolved organic matter (DOM) plays a critical role in the transport of carbon nano-particles (e.g. C 60) in the aquatic environment. However, the mechanism for C 60-DOM interactions and its environmental implications needs further investigations. In this study, the interaction of C 60 with relevant reference compounds of DOM (DOM R) is computationally simulated by molecular mechanics and density functional theory (DFT). All the C 60-DOM R complexes are firstly optimized by classical annealing, and then DFT using the Dmol 3 code. The adsorption energies of C 60 on DOM R were computed. The computed electrostatic potential indicates that DOM R are electron acceptors in the C 60-DOM R complexes, and the thermodynamic calculations indicate that electrostatic interaction is the dominant driving force for the C 60-gallic acid complexation process in water. The presence of DOM R increases the apparent water solubility of C 60. It is also observed that the C 60 apparent water solubility decrease with the increase of the energy gaps of frontier molecular orbitals ( E LUMO– E HOMO) for each C 60-DOM R complex. These findings indicate that computational simulation is an important tool for predicting the behavior and fate of carbon nano-particles in the aquatic environment.

Enhanced Dechlorination of Tetrachloroethylene by Zerovalent Silicon in the Presence of Polyethylene Glycol under Anoxic Conditions

The combination of zerovalent silicon (Si(0)) with polyethylene glycol (PEG) is a novel technique to enhance the dechlorination efficiency and rate of chlorinated hydrocarbons. In this study, the dechlorination of tetrachloroethylene (PCE) by Si(0) in the presence of various concentrations of PEG was investigated under anoxic conditions. Several surfactants including cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and Tween 80 were also selected for comparison. Addition of SDS and Tween 80 had little effect on the enhancement of PCE dechlorination, while CTAB and PEG significantly enhanced the dechlorination efficiency and rate of PCE by Si(0) under anoxic conditions. The Langmuir-Hinshelwood model was used to describe the dechlorination kinetics of PCE and could be simplified to pseudo-first-order kinetics at low PCE concentration. The rate constants (k(obs)) for PCE dechlorination were 0.21 and 0.36 h(-1) in the presence of CTAB and PEG, respectively. However, the reaction mechanisms for CTAB and PEG are different. CTAB could enhance the apparent water solubility of PCE in solution containing Si(0), leading to the enhancement of dechlorination efficiency and rate of PCE, while PEG prevented the formation of silicon dioxide, and significantly enhanced the dechlorination efficiency and rate of PCE at pH 8.3 ± 0.2. In addition, the dechlorination rate increased upon increasing PEG concentration and then leveled off to a plateau when the PEG concentration was higher than 0.2 μM. The k(obs) for PCE dechlorination by Si(0) in the presence of PEG was 106 times higher than that by Si(0) alone. Results obtained in this study would be helpful in facilitating the development of processes that could be useful for the enhanced degradation of cocontaminants by zerovalent silicon.

Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Poorly water-soluble drugs, such as phenylephrine, offer challenging problems for buccal drug delivery. In order to overcome these problems, particle size reduction (to the nanometer range) and cyclodextrin complexation were investigated for permeability enhancement. The apparent solubility in water and the buccal permeation of the original phenylephrine coarse powder, a phenylephrine–cyclodextrin complex and phenylephrine nanosuspensions were characterized. The particle size and particle surface properties of phenylephrine nanosuspensions were used to optimize the size reduction process. The optimized phenylephrine nanosuspension was then freeze dried and incorporated into a multi-layered buccal patch, consisting of a small tablet adhered to a mucoadhesive film, yielding a phenylephrine buccal product with good dosage accuracy and improved mucosal permeability. The design of the buccal patch allows for drug incorporation without the need to change the mucoadhesive component, and is potentially suited to a range of poorly water-soluble compounds.

CdSe quantum dots capped PAMAM dendrimer nanocomposites for sensing nitroaromatic compounds

The detection of nitroaromatic compounds, best known as raw materials in explosives preparations, is important in many fields including environmental science, public security and forensics. CdSe quantum dots capped with PAMAM-G4 dendrimer were synthetized in water and used for the detection of trace amounts of three nitroaromatic compounds: 4-methoxy-2-nitrophenol (MNP), 2-amine-5-chloro-1,3-dinitrobenzene (ACNB) and 3-methoxy-4-nitrobenzoic acid (MNB). To increase the apparent water solubility of these compounds α-cyclodextrin (α-CD) was used to promote the formation of inclusion complexes. The studied nitroaromatic compounds (plus α-CD) significantly quenched the fluorescence intensity of the nanocomposite with linear Stern–Volmer plots. The Stern–Volmer constants (standard deviation in parenthesis) were: MNB, KSV=65(5)×104M−1; ACNB, KSV=19(2)×104M−1; and, MNP, KSV=33(1)×102M−1. These constants suggest the formation of a ground state complex between the nitroaromatric compounds and the sensor which confers a relatively high analytical sensitivity. The detection sensibilities are about 0.01mgL−1 for MNB and ACNB and about 0.1mgL−1 for MNP. No interferences or small interferences are observed for trinitrotoluene [KSV=10(2)×102×M−1], 2,4-dinitrotoluene [KSV=20(3)×10M−1], 2,6-dinitrotoluene [KSV=11(4)×10M−1] and nitrobenzene [KSV=2(1)×103×M−1].

An alternative cyclodextrin based formulation for oral anticancer drug exemestane: In vitro and cell culture studies

summary Exemestane (EXE) is an irreversible aromatase inactivator used for the treatment of postmenopausal breast cancer. EXE is orally active but its bioavailability is about 5% due to its low solubility in water. It is known that cyclodextrin (CD) complexation enhances oral bioavailability of poorly soluble drugs. Thus, it was aimed to design and develop cyclodextrin complexes containing EXE and prepare a novel tablet formulation to improve aqueous solubility, dissolution and in vitro permeability. Introduction Estrogen suppression is an important approach to the management of hormone-responsive cancer. Therefore, aromatase inhibition is a well-established therapeutic option in postmenopausal, hormone dependent breast cancer [1]. EXE is an orally active aromatase inactivator, which is absorbed 42% from the gastrointestinal tract and preclinical data indicated that the absolute bioavailability was about 5% due to its low solubility in water and the first pass effect through liver [2,3]. Cyclodextrins (CD) are enzymatic degradation products of starch with a hydrophilic outer surface and an apolar cavity. CDs have the ability to interact with poorly water-soluble drugs and drug candidates resulting in an increase in their apparent water solubility and dissolution rates. It is also reported that CDs show permeability enhancer effects and that they can be considered practically nontoxic upon oral administration [4]. In this study, EXE's inclusion complexes were prepared and characterized using different CD derivatives (methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD)) and different preparation techniques and consequently a new tablet formulation was developed using the inclusion complex with optimal dissolution and permeation properties. Experimental methods Phase solubility studies: 0, 5,10,15, 20, 25, 30%w/v solutions ofM-β-CD,HP-β-CD andHP-γCD, all in distilled water, were added to 25 mg EXE and magnetically stirred. 7 days after which 1 mL CD drug suspensions from each vials were filtered through 0.45 μm polycarbonate membrane filter fitted in a stainless still filter holder. The experiments were performed with three replications. The filtrates were quantitatively analysed by an HPLCmethod for EXEwhichwas validated previously [5]. The apparent stability constants (K1:1) of the complexes were calculated. Preparation of inclusion complexes: The inclusion complexes of EXE with either methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) were prepared by both kneading and coprecipitation methods [6] and the molar ratio of EXE:CDs were 1:1. Physical mixtures were also prepared. Characterization of inclusion complexes: Differential scanning calorimetry (DSC), Fourier transformationinfrared spectroscopy (FTIR), Proton NMR spectrometry (H NMR), Scanning electron microscopy (SEM), and X-Ray diffractometry were used to characterize both the complexes and the physical mixtures. Preparation of tablet formulation: Since phase solubility studies, solid state characterization techniques and dissolution studies indicate that M-β-CD and kneading method show the optimumresults, a tablet formulationwas developed using EXE:M-β-CD kneaded (MBK) inclusion complex. Avicel pH 102, Sodium Starch Glycolate and Magnesium Stearate were used as tablet excipients. No solubility enhancer was added to the formulation. The tablets were prepared by direct compression method. Dissolution study of inclusion complexes and tablets: Dissolution studies for EXE, EXE complexes, EXE: M-β-CD tablets and Aromasin® tablets were carried out with six replications. The dissolution medium was 900 mL of 0.5% sodium lauryl sulphate solution (SLS) and 900 mL of distilled water at 37 °C. The difference factors (f1) and the similarity factors (f2) were calculated for tablet formulations to compare dissolution profiles. Transport/permeability studies with Caco-2 cells: Caco-2 cell culture studies were performed on EXE, EXE:CD inclusion complexes which were prepared by kneading method with both M-β-CD, HP-β-CD and HP-γ-CD. Apparent permeability coefficient (Papp:cm/s) was calculated. Statistical analysis of data was performed by Kruskal Wallis One Way Variance Analysis. Result and discussion Phase solubility studies showed that the solubility of EXE increased linearly as a function of the CD concentration, a feature of AL-type complexes. K1:1 was found to be 3722.25M-1 forM-β-CD, 3728.16M-1 for HP-β-CD and 3729.22 M-1 for HP-γ-CD. EXE's solubility with M-βCDwas found tobe 513 times better than EXE. Corresponding solubility diagrams of EXE with M-β-CD, HP-β-CD and HP-γ-CD are presented respectively in Fig. 1. Abstracts / Journal of Controlled Release 148 (2010) e74–e84 e83

Physical Characterization of 1,3-dipropyl-8-cyclopentylxanthine (CPX).

1,3-dipropyl-8-cyclopentylxanthine (CPX) has been shown to stimulate in vitro CFTR activity in F508 cells. Data from a phase I study demonstrated erratic bioavailability and no measurable clinical response to oral CPX. One cause for its poor bioavailability may have been dissolution rate limited absorption, but there is little published physicochemical data on which to base an analysis. The objective of this study was to determine the solubility and solid-state characteristics of CPX. CPX is a weak acid with pKa of 9.83 and water solubility at pH 7.0 of 15.6 microM. Both laureth-23 and poloxamer 407 increased the apparent water solubility linearly with increasing concentrations. CPX exists in two crystal forms, one of which (form II) has been solved. Form II is a triclinic crystal with space group P1 and calculated density of 1.278 g/cm(3). X-ray powder diffraction and differential scanning calorimetry studies (DSC) indicated that CPX crystals prepared at room temperature were mixtures of forms I and II. DSC results indicated a melting point of approximately 195 degrees C for form I and 198 degrees C for form II. Thermogravimetric analysis indicated no solvent loss upon heating. Dynamic water vapor sorption data indicated no significant water uptake by CPX up to 90% RH. Analysis of the data indicates that CPX may not be amenable to traditional formulation approaches for oral delivery.

Ethyl-paraben and nicotinamide mixtures: Apparent solubility, thermal behavior and X-ray structure of the 1:1 co-crystal

This work aims at investigating the nicotinamide (NA)–ethyl‐paraben (EP) binary system both in solution and in the solid state. In particular, the apparent EP solubility in water was studied in the presence of different NA concentrations (between 0.28 and 1.64 M). It was found that the apparent EP solubility increase (nearly twofold) observed at the highest NA concentration tested can be ascribed to a change in the polarity of the solvent mixture, rather than to a direct effect of NA on EP. The effect of fusion and re‐crystallization from water or ethanol solutions on EP and NA mixtures was investigated by means of differential scanning calorimetry, elemental analysis and X‐ray diffraction both on powder and single crystal. It was discovered that EP and NA form a co‐crystal having a 1:1 molar composition that can be easily crystallized from ethanol. Single crystal X‐ray analysis of this species revealed that the NA and EP molecules form corrugated layers within which the two components are intimately associated by a dense network of hydrogen bonds. In the presence of an excess NA in solution, the EP‐NA co‐crystal has lower water solubility with respect to both the single co‐crystal formers and precipitates in aqueous solutions at ambient temperature. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4830–4839, 2008

Influence of compost amendment on pyrene availability from artificially spiked soil to two subspecies of Cucurbita pepo

The dissolved organic matter (DOM) fraction of soil organic matter (SOM) may positively contribute to polycyclic aromatic hydrocarbons (PAHs) bioavailability. This work investigated the effects of DOM-rich and PAHs-free compost amendment on the plant uptake of pyrene. Two subspecies of Cucurbita pepo (ssp. pepo cv. Raven and ssp. texana cv. Sunray) were grown for three weeks in a spiked soil containing 83.9 mg kg − 1 pyrene under four different treatments; inorganic fertilizer (IF) alone, 15% (v/v) mixed gardening compost with IF (MX15% + IF), MX30% alone, and no fertilization (NF). Equilibrium pyrene desorptions from a spiked soil (104 mg kg − 1 ) under different concentrations (35–590 mg-C L − 1 ) of DOM extracts derived from two types of composts including MX and cow manure were also conducted. After harvest, the decrease in the pyrene concentration of the soil ranged from 46–65% for the different treatments. The total dry biomass for both plants was highest under MX15% + IF. The bioconcentration factors of pyrene for both also tended to decrease with increasing MX dose from 15% to 30%. However, the total uptakes of pyrene with IF and MX15% + IF were not statistically different (36.7 and 33.7 µg for Raven, and 5.20 and 7.90 µg for Sunray, respectively). These values were around 100% higher than that with NF (17.4 µg for Raven and 2.0 µg for Sunray). The pyrene desorption data confirmed the ability of DOM to associate with pyrene as indicated by its increase in apparent water solubility. On the basis of these results, MX application at 15% (v/v) does not significantly reduce the phytoextraction of pyrene due to the enhancement of plant growth as well as the possible contribution of DOM fractions to pyrene bioavailability. The application of compost may not pose serious concerns regarding the efficiency of phytoremediation of PAHs-polluted soil.

Supercritical Extraction of Carotenoids from Rosa canina L. Hips and their Formulation with β-Cyclodextrin

The purpose of this research was to preliminary assess the suitability of a new method for the preparation of a solid formulation in form of powder composed by beta-cyclodextrin and the supercritical extract of Rosa canina hips. The method implies the extraction of carotenoids, in particular beta-carotene, from freeze dried fruits of R. canina with supercritical CO2 at 70 degrees C and 300 bar, in the presence of varying quantity of ethanol as entrainer. The obtained supercritical solution is then expanded at ambient conditions into an aqueous solution of beta-cyclodextrin to favour the interaction between beta-cyclodextrin and the lipophilic components of the extract. beta-carotene solubility (mole fraction) in supercritical CO2 or in supercritical CO2/ethanol mixtures were in the order of 1 10(-7). The beta-carotene extracted from R. canina fruits (nearly 10 microg/g of dry matrix), interacts almost quantitatively with beta-cyclodextrin affording a solid phase, which presents a low apparent solubility in water. Finally the interaction with beta-cyclodextrin results in a higher concentration of the beta-carotene trans- form relative to the cis- form in the extracted product when collected in an aqueous solution of beta-cyclodextrin with respect to the extract in n-hexane.