Evaluation the effect of cyclodextrin complexation on aqueous solubility of fluorometholone to achieve ophthalmic solution

In this study, the effect of different CDs including α-CD, β-CD, γ-CD, hydroxypropyl β-CD (HP β-CD), sulphobutylether β-CD (SBE β-CD) and HP γ-CD on aqueous solubility of fluorometholone (Flu) was investigated. Also the phase solubility studies were performed in the presence of eye drop excipients such as benzalkonium chloride, hydroxypropyl methylcellulose (HPMC) and buffers. The aqueous solubility of Flu was increased by 8, 15, 5, 100, 65 and 135 folds in the presence of 20% w/v α-CD, β-CD, γ-CD, HP β-CD, HP γ-CD and SBE β-CD, respectively. Aqueous solubility of Flu was 0.43 ± 0.08 and 1.16 ± 0.04 mg/mL in systems containing 5% w/v HP γ-CD and SBE β-CD, respectively. The aqueous solubility of Flu in the presence of HP γ-CD was not influenced by buffer type while the phosphate buffer caused a reduction in the aqueous solubility in the presence of SBE-β-CD. Also, investigations on the solubility of Flu in water in the presence of 5% HP γ-CD and SBE-β-CD and the additives such as benzalkonium chloride and HPMC indicated that these components had no remarkable effect on the aqueous solubility of Flu. In conclusion, CD complexation is able to improve the aqueous solubility of Flu and it would be possible to prepare ophthalmic solution of Flu by this method.     

Polarographic behaviour and determination of beclomethasone dipropionate

The polarographic behaviour of beclomethasone dipropionate in Britton-Robinson buffers containing 40% methanol as a solubilizer has been studied. Over the pH range 1.8–12, a cathodic wave was produced, which was characterised as being irreversible, diffusion controlled and free from adsorption phenomena. The number of electrons involved in the reduction was found through comparative study with spironolactone. Using direct current polarographic mode, the limiting current concentration plot is rectilinear over the range 2.5 × 10^–5 to 4 × 10^–4 mol/1 with a detection limit of 2.5 × 10^–6 mol/1. A method has been developed for the determination of the drug in aerosols and creams, the results being in agreement with those obtained by the official method.     

相溶解度法研究环糊精对蒽醌药物的增溶作用

通过相溶解度法,测定1,2-二氨基蒽醌、1,4-二氨基蒽醌和1,8-二羟基蒽醌在不同温度、不同浓度的β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)以及羟乙基-β-环糊精(HE-β-CD)中的溶解度,绘制相溶解度曲线,并进行回收率及稳定性实验.实验结果表明:1,2-二氨基蒽醌、1,4-二氨基蒽醌和1,8-二羟基蒽醌的溶解度均随3种环糊精浓度的增加而呈线性增加,相溶解度曲线为AL型,蒽醌与环糊精形成的包合物类型为1∶1型,3种环糊精对蒽醌均有增溶作用,增溶效应顺序为HP-β-CDHE-β-CDβ-CD,与HP-β-CD作用顺序为1,2-二氨基蒽醌1,4-二氨基蒽醌1,8-二羟基蒽醌.     

Enhancement of cyclosporine aqueous solubility using α- and hydroxypropyl β-cyclodextrin mixtures

Cyclodextrins (CDs) are cyclic oligosaccharides that form inclusion complexes with lipophilic molecules through their hydrophobic central cavity. In this study, the effect of α-CD, hydroxylpropyl-β-CD (HP-β-CD) and mixtures of these two CDs on the aqueous solubility of cyclosporine A (CyA) was investigated. Infrared spectroscopy and thermal analysis were used to confirm CyA-CD complex formation. CyA aqueous solubility was increased by 10 and 80 fold in the presence of α-CD and HP β-CD, respectively. The phase-solubility profile for HP-β-CD was linear while that for α-CD had positive deviation from linearity. In the presence of constant concentration of α-CD (15% w/v), aqueous solubility of CyA was further increased upon addition of HP-β-CD up to a concentration of 20% w/v. At higher HP-β-CD concentrations, aqueous solubility of CyA was observed to decrease. Addition of sodium acetate (up to 5% w/v) to aqueous solutions containing 20% w/v HP-β-CD and increasing concentrations of α-CD resulted in a significant reduction in CyA solubility. Complex formation between CyA and both α-CD and HP-β-CD was confirmed by differential scanning calorimetry (DSC). No significant changes were observed in the IR spectra of either CyA or CD following complex formation suggesting chemical interaction between CyA and the CD was unlikely. Phase-solubility studies showed that α-CD had a much greater effect on the solubility of CyA than HP-β-CD. Addition of HP-β-CD to aqueous solutions of α-CD affected the solubility of CyA in these systems. A mixture of 15% w/v α-CD and 20% w/v HP-β-CD was optimal for increasing aqueous solubility of CyA.     

The effect of acidity on micellization in dodecyldimethylamine oxide-sodium dodecyl sulfate aqueous mixtures

The effect of acidity on micellization in aqueous solutions of dodecyldimethylamine oxide-sodium dodecyl sulfate mixtures is studied. The CMC values are determined for acidic and nonacidified solutions at 50 °C and different ratios of two surfactants. The measurements are taken using potentiometry, conductometry, and tensiometry techniques. The CMC values are calculated within the framework of a quasi-chemical model of micellization modified with regard to the specific features of the system under consideration. Nonacidified solutions are modeled as a mixture of anionic and nonionic surfactants, whereas acidic solutions are treated as a mixture of anionic and cationic surfactants. The results of model calculations are in satisfactory agreement with the experimental data.     

Increasing the solubility characteristics of fenofibrate with cyclodextrin

The incidence of genetic lipoprotein disorders, or hyperlipoproteinaemia, is currently increasing. Examinations were carried out on the hyperlipoproteinaemic drug fenofibrate and various cyclodextrin derivatives were applied to increase the solubility of this drug. Numerous products with several compositions (drug: CD mole ratio=2:1, 1:1, 1:2 or 1:3) were studied and three preparation methods (powder mixing, kneading and precipitation) were used. In vitro drug liberation and membrane diffusion examinations revealed compositions suitable for the preparation of a capsule dosage form (1:2 and 1:3 physical mixtures).Dedicated to Dr. Béla Selmeczi, university professor, with the best wishes for his 65th birthday.     

Increasing the solubility of drugs through cyclodextrin complexation

The bioavailability of pharmaca which dissolve in water only with difficulty is very limited. The cyclodextrins /CDs/, and primarily -CD and -CD, were successfully applied to increase the dissolution characteristics and hence the bioavailability of drugs: furosemide, hydrochlorothiazide, mebendazole, metronidazole, spironolactone, tofisopam, vinpocetine base, etc. From these pharmaca, products were made by mixing, kneading, grinding, freeze-drying, spray-embedding and precipitation.The more important factors on which the dissolution and bioavailability of the drugs depend are concluded.     

The solubility of toluene in aqueous salt solutions

The solubility of toluene has been measured in distilled water, and in various inorganic salt solutions. Values of the Setschenow constant, K(S), which quantify toluene solubility versus salt concentration, have been determined for each salt. Values of K(S) are compared to the activity of water for the salt solutions. Data from this study, consistent with earlier data, suggests that the effects of salts upon toluene solubility are non-additive. This contrasts the additive behavior of inorganic salts upon the solubility of nonpolar organic compounds, such as benzene and naphthalene, reported in the literature. Specific interaction between slightly polar toluene and ions in solution is suggested as a possible explanation for the non-additive effect of salts on the solubility of toluene.     

The solubility of oxygen in aqueous fluorocarbon emulsions

The solubility of oxygen in aqueous fluorocarbon emulsions has been measured directly for several perfluorocarbons and monobromo or monoiodo-perfluorocarbons. The measured oxygen solubilities are consistent with results for the solubility of oxygen in neat liquid perfluorinated organic compounds.     

Simultaneous determination of beclomethasone, beclomethasone monopropionate and beclomethasone dipropionate in biological fluids using a particle beam interface for combining liquid chromatography with negative-ion chemical ionization mass spectrometry

A new simple and sensitive assay has been developed for the simultaneous quantitative measurement of beclomethasone dipropionate and its hydrolysis products in human plasma and urine. Beclomethasone 17.21-dipropionate, beclomethasone 17-monopropionate, beclomethasone and the internal standard, dexamethasone 21-acetate, were measured by combined liquid chromatography and negative-ion chemical ionization mass spectrometry with methane as the reagent gas. A particle beam interface from Hewlett Packard was used. Under mild operating conditions, abundant and stable characteristic high-mass ions were generated in the ion source of the mass spectrometer by a resonance electron-capture mechanism. The fast extraction procedure requires 1 ml of plasma or urine, and the quantification limit of the method is 1 ng ml-1 for the three tested compounds.     

The effect of potential aqueous pollutants on the solubility of Pb+2 in cerussite—Calcite phase

The results of this work show:

1. Pb⁺² is rapidly immobilized from aqueous solutions using calcite or aragonite, CaCO₃, and the Pb⁺² is precipitated as PbCO₃ (cerussite) on the surface of the CaCO₃ (the Pb⁺²-CaCO₃ phases),
2. using CaCO₃, the concentration of Pb⁺² in certain solutions can be reduced below environmentally tolerated concentrations, and
3. organics present in solutions and natural waters can mobilize Pb⁺² from Pb⁺²-calcite phases; with effluent waters from a paper factory, and 1:1 Ca⁺²-EDTA being more effective than lignin sulfonates, 1:1 Ca⁺²-tartrate, soap, detergent, water from a sewage treatment plant, and ordinary river water.

     

Thermal properties of betulin dipropionate and its mixtures with polymers

Melting of betulin dipropionate (3β,28-di-O-propionyl-lup-20(29)-lupene) of high purity (orthorhombic P2₁2₁2₁, a = 1.27409(2), b = 1.57316(3), c = 1.59810(3) nm) and its mixtures with four excipients was investigated with DSC and TG. Melting point is 163.6 °C (?_f H = 33 kJ mol^?1). Smaller values reported recently were measured for not pure samples. The melt of betulin dipropionate remains glassy under ambient conditions and does not crystallize during the second heating. In mixture with excipients (arabinogalactan, polyethylene glycol, polyvinylpyrrolidone, and fumed silica), the betulin dipropionate loses its crystal structure after mechanical activation.     

Improved aqueous Cannizzaro reaction in presence of cyclodextrin

An aqueous hydroxypropyl-??-cyclodextrin solution has been used to increase the conversion of 4-biphenylcarboxaldehyde into the corresponding alcoholic and carboxylic substrates, by means of a Cannizzaro reaction. The observed enhancement has been ascribed to a partial solubilization of 4-biphenylcarboxaldehyde. In addition, as the main part of the organic substrates still remains insoluble, synthesized products are easily recovered by filtration. As a consequence, the basic cyclodextrin solution might also be reused for a new synthetic cycle, without significant loss of conversion. Aqueous solid?Cliquid biphasic reaction in presence of cyclodextrins thus seems to be a promising tool in the green chemistry field.     

The acidity and solubility constants of tetracyclines in aqueous solutions

Solubility measurements over the pH range 2.6–7.6 for tetracycline, chlortetracycline, dimethylchlortetracycline and oxytetracycline are used to determine thermodynamic values for the solubility constant and the first and second acidity constants of these compounds.     

UV-spectrophotometric determination of beclomethasone dipropionate and phenylethyl alcohol in a nasal spray by inverse least-squares regression

Inverse least-squares (ILS) regression was used for the simultaneous UV spectrophotometric determination of the active principle (beclomethasone dipropionate) and a solvent (phenylethyl alcohol) in a pharmaceutical preparation commercially available in nasal spray form. A factorial design was used to establish the calibration equations, which enables the construction of calibration models using a minimum number of samples. The operating wavelengths were chosen by first choosing that coinciding with the absorption maximum for the analyte to be determined and then adding terms, one at a time, following the stepwise-forward procedure until no significantly improved S.E. is obtained. Single calibration equations were found for both constituents that provide satisfactory results in absorbance mode. The ILS procedure was applied to five industrial preparations with highly satisfactory results. In all, coefficients of variation values were less than 2%.     

The thermal stability of triprolidine hydrochloride and its mixtures with cyclodextrin and glucose

Triprolidine hydrochloride (C₁₉H₂₂N₂·HCl·H₂O) (TPH) is a well-known antihistamine drug which is reported as being photosensitive. The thermal stabilities of TPH and of 1:1 molar and 1:1 mass ratio physical mixtures of TPH with β-cyclodextrin (BCD) and with glucose have been examined using DSC, TG and TG-FTIR, complemented by X-ray powder diffraction (XRD) and infrared spectroscopic (IR) studies. Thermal studies of the solid TPH/BCD mixtures indicated that interaction between the components occurs and it is possible that the TPH molecule may be least partially accommodated in the cavity of the BCD host molecule. XRD results support this indication of inclusion. The results of molecular modelling suggest that TPH is most likely to be accommodated in the BCD cavity as a neutral triprolidine molecule with the toluene portion of the molecule preferentially included in the cavity. The results obtained illustrate the general stability of TPH. The study has also shown TPH to be compatible with both glucose and BCD, which are potential excipients both in solid and liquid dosage forms. The presence of these excipients in dosage forms will thus not adversely affect the stability and the therapeutic efficacy of TPH. This revised version was published online in July 2006 with corrections to the Cover Date.