Solid-State Preparation and Characterization of 2-Hydroxypropylcyclodextrins-Iodine Complexes as Stable Iodophors.

The use of iodine as antiseptic poses some issues related to its low water solubility and high volatility. Stable solid iodine-containing formulations are highly advisable and currently limited to the povidone-iodine complex. In this study, complexes of molecular iodine with 2-hydroxypropyl α-, ß- and γ-cyclodextrins were considered water-soluble iodophors and prepared in a solid state by using three different methods (liquid-assisted grinding, co-evaporation and sealed heating). The obtained solids were evaluated for their iodine content and stability over time in different conditions using a fully validated UV method. The assessment of the actual formation of an inclusion complex in a solid state was carried out by thermal analysis, and the presence of iodine was further confirmed by SEM/EDX and XPS analyses. High levels of iodine content (8.3-10.8%) were obtained with all the tested cyclodextrins, and some influence was exerted by the employed preparation method. Potential use as solid iodophors can be envisaged for these iodine complexes, among which those with 2-hydroxypropyl-α-cyclodextrin were found the most stable, regardless of the preparation technique. The three prepared cyclodextrin-iodine complexes proved effective as bactericides against S. epidermidis.

Degradation profile of nepafenac in aqueous solution and structural characterization of a novel degradation product.

The stability of the anti-inflammatory drug nepafenac was investigated in aqueous solutions containing hydroxypropyl-ß-cyclodextrin at three different values of pH and degradation products were identified. (2-Amino-3-benzoyl)-oxoacetic acid, previously not reported as nepafenac-related impurity, was isolated and structurally characterized by NMR and ESI-MS analyses. It was also shown that the formation of this α-ketoacid from nepafenac in alkaline water/organic cosolvent solution occurs through an aerobic oxidation of the key intermediate 7-benzoyl-1,3-dihydro-indol-2-one, which in some extent is protected from oxidation in the presence of the cyclodextrin additive.

Polyphenolic Fraction from Olive Mill Wastewater: Scale-Up and in Vitro Studies for Ophthalmic Nutraceutical Applications.

The valorization of food wastes is a challenging opportunity for a green, sustainable, and competitive development of industry. Approximately 30 million m3 of olive mill wastewater (OMWW) are produced annually in the world as a by-product of the olive oil extraction process. In addition to being a serious environmental and economic issue because of their polluting load, OMWW can also represent a precious resource of high-added-value molecules such as polyphenols that show acclaimed antioxidant and anti-inflammatory activities and can find useful applications in the pharmaceutical industry. In particular, the possibility to develop novel nutraceutical ophthalmic formulations containing free radical scavengers would represent an important therapeutic opportunity for all inflammatory diseases of the ocular surface. In this work, different adsorbents were tested to selectively recover a fraction that is rich in polyphenols from OMWW. Afterward, cytotoxicity and antioxidant/anti-inflammatory activities of polyphenolic fraction were evaluated through in vitro tests. Our results showed that the fraction (0.01%) had no toxic effects and was able to protect cells against oxidant and inflammatory stimulus, reducing reactive oxygen species and TNF-α levels. Finally, a novel stable ophthalmic hydrogel containing a polyphenolic fraction (0.01%) was formulated and the technical and economic feasibility of the process at a pre-industrial level was investigated.

Effect of cyclodextrin additives on azithromycin in aqueous solution and insight into the stabilization mechanism by sulfobutyl ether-ß-cyclodextrin.

The stability of azithromycin in buffered aqueous solution at pH 6.7 was investigated in the presence of different cyclodextrin (CD) additives by HPLC monitoring of the drug concentration over time. In the presence of γ-CDs, either in native or derivatized form, the long-term stability of azithromycin was sensibly decreased with respect to the reference sample without any additives, whereas the opposite effect was observed with all the three tested ß-CDs. The most effective stabilization of the drug was obtained by using sulfobutyl ether-ß-cyclodextrin, which allowed a concentration of azithromycin in solution at 99% up to 6 months at room temperature. The positive action of sulfobutyl ether-ß-cyclodextrin was mainly exerted through the suppression of a degradation pathway leading to the opening of lactone ring of azithromycin. The formation of dynamic inclusion complexes in solution was ruled out by NMR data and stabilization of azithromycin by the amphiphilic sulfobutyl ether-ß-cyclodextrin through surfactant-like effects was proposed on the basis of the strict similarity, either in the degradation profiles and in the NMR data, with a solution of the drug in the presence of sodium hexylsulphonate as surfactant.

pH-Dependent stability of azithromycin in aqueous solution and structure identification of two new degradation products.

The degradation profile of azithromycin in buffered solutions was investigated using HPLC and found to be pH dependent in the range of 6.0-7.2. Desosaminylazitromycin, derived from hydrolytic loss of cladinose of the parent molecule, was the major degradation product at pH 6.0 but its amount progressively decreased moving toward pH 7.2. Two additional unreported degradation products were also observed and their structures were fully elucidated by MS- and NMR-spectroscopy to be associated with opening of the macrocyclic lactone ring.