S. Tommasini

Improvement in solubility and dissolution rate of flavonoids by complexation with β-cyclodextrin

The inclusion into the beta-cyclodextrin is used to improve pharmacokinetic characteristics of hesperetin and naringenin. Solubility of hesperetin and naringenin with increasing concentrations of beta-cyclodextrin grows as long as the temperature increased. Stability constants were determined by the solubility method by Higuchi and Connors at different temperatures, and the thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. The solid complexes were obtained in a molar ratio of 1:1 and their dissolution behavior at different pH was examined.

Solid-state study of polymorphic drugs : carbamazepine

Polymorphs of a compound have solid crystalline phases with different internal crystal lattices; in pharmaceuticals, differences due to polymorphism and pseudopolymorphism can affect bioavailability and effective clinical use. The aim of this work was to obtain the different polymorphic modifications of the anticonvulsant drug, carbamazepine, and to characterise them by means of typical structure-sensitive analytical techniques, such as FT-IR spectroscopy, XRPD and DSC. Further investigations were also performed by Hot Stage FT-IR thermomicroscopy, which permitted the visible and spectroscopic characterisation of the polymorphic forms during heating. Our results confirm the existence of three different polymorphic forms for anhydrous carbamazepine: Form III, the commercial one, Form I, obtained by heating Form III and Form II, crystallised from ethanolic solution. Substantial differences were detected among the polymorphs with regard to solid-state properties. Moreover, Hot Stage FT-IR thermomicroscopy proved its analytical potential to characterise the drugs polymorphism.

Study of flavonoids/β-cyclodextrins inclusion complexes by NMR, FT-IR, DSC, X-ray investigation☆

Flavonoids are natural substances with a lot of biological activities, including the antioxidant one. Their use in pharmaceutical field is, however, limited by their aqueous insolubility. As the formation of the inclusion complexes can improve their solubility in water, the flavonoids hesperetin, hesperidin, naringenin and naringin have been complexed with beta-cyclodextrin (beta-CD) by the coprecipitation method and studied in solution and in solid state by NMR, FT-IR, differential scanning calorimetry and X-ray techniques. The effects of complexation on the chemical shifts of the internal and external protons of beta-CD in the presence of each flavonoid were observed.

Study of the extraction procedure by experimental design and validation of a LC method for determination of flavonoids in Citrus bergamia juice.

A reversed-phase high-performance liquid chromatographic (HPLC) separation with photo-diode array detection was developed for the simultaneous determination of flavonoids extracted from Citrus bergamia juice. It employs a C18 reversed-phase column and a linear gradient elution system with methanol/water with 5% acetic acid (v/v), as mobile phase. The method was validated in terms of detection limits (LOD), quantitation limits (LOQ), linearity, precision and accuracy. Limits of detection ranged from a low of 0.007 mg ml(-1) (narirutin) to a high of 0.018 mg ml(-1) (didymin). The limits of quantitation were between a low of 0.011 mg ml(-1) (7-OH flavanone) and a high of 0.024 mg ml(-1) (didymin). An excellent linear response was observed over the range specified for all analytes, as confirmed by the correlation coefficient with ranged from 0.9982 and 0.9999. The intra-day R.S.D.% ranged from 0.11 to 3.64%. The intermediate precision R.S.D.% were not higher than 7.62%. The accuracy of the method was confirmed with an average recovery ranging, except for neoeriocitrin, between 88.07% and 102.45%. Since the extraction conditions can affect analyte recovery, a suitable optimization strategy of the procedure was needed. The experimental parameters optimized were extraction time, temperature, and solvents. A multivariate approach was used to provide direct evaluation of the selected variables and related interactions. The D-optimal design was constructed by applying the exchange algorithm. All experimental results were computed by NEMROD-W software. This methodology led us to obtain the best recovery for all the flavonoids in the least number of experiments.

Comparative photodegradation studies on 3-hydroxyflavone: influence of different media, pH and light sources

3-Hydroxyflavone (3-OH-F) photochemistry in solution has been rationalized in terms of an excited state intramolecular proton transfer (ESIPT), which involves the free 3-hydroxy group interacting with the ortho-carbonyl. This photo-rearrangement occurs rapidly and is strongly influenced by the physico-chemical properties of the solvent, which plays an essential role in determining whether a photo-oxidation or a photo-induced molecular rearrangement takes place. 3-OH-F photoreactivity has been deeply investigated and the related mechanisms elucidated, as affected by various solvents, pH values and irradiation wavelengths, leading to different photodegradation rates and pathways. Moreover, the influence of molecular encapsulation upon alpha- and beta-cyclodextrins (alpha- and beta-CyD) on the molecule photoreactivity has been examined, as a potential tool for increasing molecule photostability as well as minimizing photoinduced toxic effects on biosubstrates.

Study of β-blockers/β-cyclodextrins inclusion complex by NMR, DSC, X-ray and SEM investigation ☆

Abstract The formation of inclusion complexes between β-cyclodextrin with the two β-blockers, atenolol and celiprolol, have been studied in the aqueous environment and in the solid state by nuclear magnetic resonance (NMR) spectroscopy, X-ray, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) techniques. The magnitude of the chemical shifts of the interior and exterior β-cyclodextrin protons in the presence of each β-blocker indicated that these are included within the β-cyclodextrin cavity. In aqueous solution they form 1:1 complexes. In the solid state the formation of the β-cyclodextrin/atenolol (celiprolol) complexes is confirmed by X-ray, DSC and SEM, also employed to characterize pure substances and their physical mixtures.

Validation of a LC method for the analysis of zafirlukast in a pharmaceutical formulation.

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for estimation of zafirlukast in a pharmaceutical formulation. Assay samples were extracted utilizing acetonitrile. Drug and internal standard were chromatographed on reversed-phase C18 columns, using mixtures of acetonitrile/water and the eluents were monitored at different wavelengths. The method was validated statistically for its linearity, accuracy, robustness and precision. Experimental design was used during validation to evaluate method robustness and for the determination of intermediate precision. Factors examined for statistical approaches include laboratory, day, analyst, instrument, different percentage of organic modifier, temperature, wavelength and flow-rate. Due to its simplicity and accuracy, the method may be used for routine quality control analysis.

Validation of a LC method for the analysis of oxaliplatin in a pharmaceutical formulation using an experimental design

A rapid and sensitive RP-HPLC method with UV detection for routine control of oxaliplatin in a pharmaceutical formulation (Eloxatin) was developed. Quantitation was accomplished with the internal standard method. The procedure was validated by linearity (correlation coefficient=0.999948), accuracy, robustness and intermediate precision. Experimental design was used during validation to calculate method robustness and intermediate precision. For robustness test three factors were considered: percentage v/v of acetonitrile, flow rate and temperature; an increase in the flow rate results in a decrease of the drug found concentration, while the percentage of organic modifier and temperature have no important effect on the response. For intermediate precision measure the considered variables were: analyst, equipment and days. The RSD value (2.27%, n=24) indicated a good precision of the analytical method.

Enantiomeric resolution of anti-HIV agents on a cellulose derivative chiral stationary phase

SummaryAnti-HIV enantiomeric 1H, 3H-thiazolo[3, 4-a] benzimidazoles have been stereospecifically analyzed by elution on a column of cellulose tris-(4-methyl-phenylbenzoate)ester adsorbed on macroporous silica (ChiralcelR OJ).The enantiomeric resolution of the compounds examined is linked to a complex and competitive contribution of different factors.

Structural and spectroscopic features of lutein/butanoyl-β-cyclodextrin nanoassemblies.

Lutein, the primary carotenoid present in the central area of the retina of eye appears to be associated with the protection against age-related macular degeneration (the leading cause of blindness in older adults). Its lipophilicity and consequently its scarce water solubility (1.3×10(-9)M) represent a drawback for bioavailability. To circumvent these unfavorable characteristics, in this work lutein (Lut) have been encapsulated in amphiphilic cyclodextrin (ACyD) by following the well-established strategy of entrapping a lipophilic drug in CyD carriers. Primary face butyrate modified β-cyclodextrins (C(4:7)) form in water nanoaggregates with a average size of 250nm and a ζ-potential of about -6mV. They are able to entrap lutein at 1:6 Lut/ACyD molar ratio by yielding nanoassemblies of vesicular aspect (320nm and -8mV) such as observed by static, dynamic and electrophoretic light-scattering. UV-vis measurements revealed that electronic properties of lutein were maintained when interact with ACyD nanoaggregates. The monitoring of the entapped carotenoid leaking from ACyD nanostructures was investigated suggesting the potential of Lut/ACyD nanoassemblies in drug delivery.