Hydrophilic interaction chromatography in food matrices analysis: An updated review.

This review focuses on the most recent papers (from 2011 to submission date in 2017) dealing with the analysis of different organic components in foods (i.e. nucleobases, nucleosides, nucleotides, uric acid, and creatinine, amino acids and related compounds, choline-related compounds and phospholipids, carbohydrates, artificial sweeteners and polyphenolic compounds), using hydrophilic interaction liquid chromatography (HILIC) combined with different detection techniques. For each compound class, the investigated food matrices are grouped per: foods of animal origin, vegetables, fruits and related products, baby food, and other matrices such as drinks and mushrooms/fungi. Furthermore, the main advantages of HILIC chromatography respect to the other commonly used techniques are discussed.

Cretan tea (Origanum dictamnus L.) as a functional beverage: an investigation on antiglycative and carbonyl trapping activities.

Accumulation of advanced glycation end products (AGEs) in vivo is associated with many chronic disorders such as diabetes, renal failure, aging, and Alzheimer's disease. The aim of this study was to expand the knowledge about the functional properties of Origanum dictamnus L. beverage (Cretan tea) by an investigation about the inhibitory effects on the formation of AGEs and the capacity to trap dicarbonyl compounds. Dittany infusion was characterized for its polyphenolic composition by RP-HPLC-DAD-ESI/MSn and twenty compounds were detected. Its antiglycative property was evaluated by in vitro BSA-sugar (glucose, fructose, and ribose) and BSA-methylglyoxal (MGO) assays, tests for the formation of Amadori products and dicarbonyl compounds, and the direct glyoxal (GO) and MGO trapping capacity. The infusion showed the highest inhibitory effect on the formation of dicarbonyl compounds and AGEs (activity values range from 72-100%) and only a weak effect on the formation of Amadori products, indicating that the antiglycative action occurred primarily during the last two phases of the non-enzymatic glycation reaction. These activities are partially correlated with the antioxidant/antiradical activity, as demonstrated by the scavenger capacity against the ABTS cation and DPPH stable radicals, and the reducing power. The registered high anti-AGE capacity could probably be ascribed to the dittany polyphenolic composition particularly rich in flavone derivatives. These findings support further investigations to study the feasibility of dittany as an antiglycative agent in food or cosmetic preparation.

Artichoke (Cynara cardunculus L. var. scolymus) waste as a natural source of carbonyl trapping and antiglycative agents.

The role of polyphenolic compounds extractable from artichoke solid wastes in the formation of advanced glycation end products (AGEs) was studied. Outer bracts and stems were extracted using different water-ethanol mixtures and HPLC-DAD analyses indicated aqueous and hydro-alcoholic 20:80 stem extracts as the richest in polyphenols. The samples were characterized in their phenolic composition (using mass spectrometry) and antioxidant capacity. Antiglycative capacity was evaluated by in vitro BSA-sugars (glucose, fructose, and ribose) and BSA-methylglyoxal (MGO) tests, formation of Amadori products assay, direct glyoxal (GO) and MGO trapping capacity. Results indicated both extracts as effective inhibitors of fructosamine formation and antiglycative agents. In particular, aqueous extract showed the best activity in the systems containing glucose and fructose, differently from ethanolic extract, that was demonstrated able to better inhibit AGEs formation when ribose or MGO act as precursors. Ethanolic extract was also shown to be able to trap MGO and GO, with efficiency increasing after 24hours of incubation time. These activities are partially correlated with the antioxidant effect of the extract, as demonstrated by the scavenger capacity against ABTS cation and DPPH stable radicals; this relationship is evident when the model system, containing protein incubated with ribose or MGO, is considered. The different activities of the tested extracts could probably be ascribed to the different composition in chlorogenic acids (CQAs), being aqueous extract richer in 1-CQA, 3-CQA, and 1,3-di-CQA, and ethanolic extract in 5-CQA, caffeic acid, 1,5-di-CQA. These findings support further investigations to study the stability of the different CQAs in simil-physiological conditions and the feasibility of artichoke waste as antiglycative agents in food or pharmacological preparations. CHEMICAL COMPOUNDS: 5-caffeoylquinic acid (PubChem CID 5280633); 3-caffeoylquinic acid (PubChem CID 1794427); 1-caffeoylquinic acid (PubChem CID 10155076); 1,3-di-caffeoylquinic acid (PubChem CID 24720973); 1,5 - di-caffeoylquinic acid (PubChem CID 122685); caffeic acid (PubChem CID 689043); apigenin-7-glucuronide (PubChem CID 5319484); methylglyoxal PubChem CID (880); aminoguanidine hydrochloride (PubChem CID 2734687).

Electrospun fibers as potential carrier systems for enhanced drug release of perphenazine.

Solubility represents an important challenge for formulation of drugs, because the therapeutic efficacy of a drug depends on the bioavailability and ultimately on its solubility. Low aqueous solubility is one of the main issues related with formulation design and development of new molecules. Many drug molecules present bioavailability problems due to their poor solubility. For this reason there is a great interest in the development of new carrier systems able to enhance the dissolution of poorly water-soluble drugs. In this work, fibers containing an insoluble model drug and prepared by an electrospinning method, are proposed and evaluated to solve this problem. Two hydrophilic polymers, polyvinylpyrrolidone (Plasdone® K29/32) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used to increase the water solubility of perphenazine. The physico-chemical characterization suggests that the drug loaded in the fibers is in the amorphous state. Both polymeric carriers are effective to promote the drug dissolution rate in water, where this active pharmaceutical ingredient is insoluble, due to the fine dispersion of the drug into the polymeric matrices, obtained with this production technique. In fact, the dissolution profiles of the fibers, compared to the simple physical mixture of the two components, and to the reference commercial product Trilafon® 8mg tablets, show that a strong enhancement of the drug dissolution rate can be achieved with the electrospinning technique.

Mechanochemical synthesis of bumetanide-4-aminobenzoic acid molecular cocrystals: a facile and green approach to drug optimization.

Molecular cocrystals are of growing interest in pharmaceutics for their improved physicochemical properties. Their mechanochemical synthesis is very promising, being easy, cheap, and "green". Here, for the first time, we report on cocrystallization of bumetanide, a diuretic and natriuretic active principle, and 4-aminobenzoic acid. The synthesis is performed both by wet and dry grinding. The cocrystal formation was investigated with a wide range of techniques, including solid-state NMR, IR, XRD, microscopy, and thermal analysis. Wet and dry grinding procedures led to different cocrystal polymorphs. In particular, the dry method gave a cocrystal by powder amorphization and subsequent crystallization. DFT calculations at the B3LYP/6-31+G(d,p) level of theory shed light on the H-bond scheme at the basis of cocrystal formation. The cocrystals showed improved solubility and dissolution rate with respect to the drug alone. This could guarantee a faster absorption and a better bioavailability of the active principle.

Preparation and physicochemical characterization of acyclovir cocrystals with improved dissolution properties.

Acyclovir is a well-known antiviral agent. It can be administered in very high doses (from 200 to 1000 mg even three-four times daily). It has absorption problems mainly due to its poor solubility in water (about 0.2 g/100 mL at 25°C) and its oral bioavailability is approximately 15%-20% with a half-life of about 3 h. To improve acyclovir solubility and/or its dissolution properties, two cocrystals of this drug were successfully produced with glutaric acid (AGA1:1) and fumaric acid (AFA1:1) as conformers, using a cogrinding method. Their effective formation was investigated by a broad range of techniques: thermal analysis, Fourier transform infrared spectroscopy, X-ray powder diffraction, solid state nuclear magnetic resonance, and scanning electron microscopy coupled with energy dispersive X-ray spectrometry. The water solubility of the AGA1:1 cocrystal was not improved in comparison to acyclovir, while AFA1:1 showed a slight increased solubility at equilibrium. The main difference was detected in terms of intrinsic dissolution rates (IDR). The IDR of the new phases were much faster compared with acyclovir, particularly at neutral pH. AFA1:1 showed the most rapid dissolution behavior in water; within 10 min, the drug was released completely, while just 60% of acyclovir was dissolved in 1 h.

I. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: nanoparticles and co-mixing.

Nateglinide is a non-sulphonylurea insulinotropic oral antidiabetic agent. The main problem in formulating an oral dosage form is its low solubility in aqueous media. This problem is particularly critical for an anti-diabetic drug because it should be administered just before the meals and be quickly bioavailable to cover the post-prandial glycemic peak. In this work, some technological approaches have been studied to improve the dissolution rate of nateglinide. Furthermore, two different polymorphs of nateglinide (H and B) have been tested to evaluate the influence of the crystal habitus on the dissolution behavior of the drug. The results have clearly demonstrated that wettability plays a key role in the dissolution behavior of nateglinide. As a matter of fact the physical dispersion of the drug with colloidal silica or hydrophilic swellable polymers strongly enhances the dissolution rate of nateglinide. The two polymorphs tested did not show significant differences in terms of dissolution behavior.

Structure and properties of domperidone and its succinate salt.

This paper describes the structure and properties of the drug domperidone and a novel 1:1 domperidone succinate salt. The new salt is characterized by means of thermal, spectroscopic, microscopic and powder diffraction measurements. The crystal structures of the salt and, for the first time, of pure domperidone have been determined by means of single-crystal X-ray diffraction. In both structures, the piperidine ring of domperidone adopts the expected chair conformation, and supramolecular centrosymmetric R2(2)(8) motifs are formed by N-H...O hydrogen bonds between chlorine-substituted oxobenzimidazolyl groups. Further N-H...O hydrogen bonds occur between non-substituted oxobenzimidazolyl groups and the resulting C(4) motifs originates hydrogen-bonded chains, extending along the crystallographic b axis. In the salt, a single N-H...O hydrogen bond forms between the protonated nitrogen of the piperidine ring and the carboxylic O atom of the succinate ion. Two alternative and mutually exclusive positions for the nonsubstituted oxobenzimidazolyl group have also been observed; this disorder makes the hydrogen-bonded chains originating from the bicyclic group polar. The dissolution behaviour of the salt in dosage form is compared with two reference commercial products. The salt shows an increased solubility, a characteristic that could be of great advantage from a pharmaceutical view point.

II. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: co-milling.

Nateglinide is an oral antidiabetic agent that should be administered 10-30 min before the meal, but it shows low and pH-dependent solubility that may reduce its oral bioavailability. To improve nateglinide dissolution rate, the active was co-milled with three different super-disintegrants or with some hydrophilic excipients, in 1:1, 1:2, and 1:4 drug to carrier ratio (w:w). The three super-disintegrants were crosslinked polyvinylpyrrolidone (PVPC), sodium starch glycolate (SSG) and crosslinked carboxymethyl cellulose (CMCC). The three hydrophilic excipient were amorphous silica (AS), mannitol (M) and Poloxamer (PO). A strong enhancement of drug dissolution rate was obtained from the nateglinide:super-disintegrant co-milled systems in 1:4 ratio, which can be explained by a combination of several factors: an increase in wettability, due to the hydrophilic nature of the carriers, a possible reduction of particle size and a more intimate dispersion of the drug onto the carrier, as a result of the mechanical treatment.

An experimental and theoretical investigation of loperamide hydrochloride-glutaric acid cocrystals.

Cocrystallization is a powerful method to improve the physicochemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastrointestinal tract showing low and pH-dependent solubility; for this reason, an enhancement of its solubility or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here we prepared cocrystals of this active principle with glutaric acid and so obtained a new crystalline solid representing a viable alternative to improve the physicochemical properties and thus the pharmaceutical behavior of the drug. Differential scanning calorimetry, X-ray powder diffraction, Fourier infrared spectroscopy, solid-state NMR, and scanning electron microscopy coupled to the energy-dispersive X-ray spectrometry were used to investigate the new solid-phase formation. DFT calculations at B3LYP/6-31G(d) level of theory, in the gas phase, including frequencies computation, provided a rationale for the interaction between loperamide hydrochloride and glutaric acid. The cocrystals showed improved water solubility in comparison with loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly in comparison with three reference commercial products when tested at neutral pH values.