Valeria Ambrogi

Intercalation compounds of hydrotalcite-like anionic clays with antiinflammatory agents — I. Intercalation and in vitro release of ibuprofen

Hydrotalcite-like compounds are layered solids having positively charged layers and interlayer charge-compensating anions. The synthetic Mg0.67Al0.33(OH)2 Cl0.33.0.6H2O, which is biocompatible, has been used to intercalate a model drug, ibuprofen, in order to prepare a modified release formulation. The intercalation compound was prepared via ion-exchange starting from the chloride form of hydrotalcite and its composition, determined both by elemental microanalysis and thermogravimetric analysis, was Mg0.67Al0.33(OH)2IBU0.33.0.47H2O, drug content 50% (w/w). As a consequence of the intercalation, the interlayer distance of the host increased from 0.78 nm (interlayer distance of chloride form) to 2.17 nm. The result of dissolution tests at pH 7.5 showed that the in vitro drug release was modified if compared with that obtained with comparative formulations. The mechanism of modified drug release has been interpreted on the basis of the ion exchange process of the ibuprofen anion intercalated in the lamellar host and phosphates contained in the intestinal fluid buffer.

Intercalation compounds of hydrotalcite-like anionic clays with anti-inflammatory agents, II: Uptake of diclofenac for a controlled release formulation

The purpose of this study was to investigate whether hydrotalcite is able to intercalate diclofenac, a nonsteroidal anti-inflammatory drug, and release it in a controlled manner. Layered Mg−Al hydrotalcite in the chloride form was used as a host, and the intercalation compound was prepared by Cl−/diclofenac anionic exchange. Drug release from the intercalation compound was performed in vitro in simulated intestinal fluid at pH 7.5 according to USP 24 and in a pH 7.0 solution designed to mimic the ionic conditions of the small intestine. Results from the intercalation process show that hydrotalcite is able to intercalate diclofenac with a simple procedure and with a good drug loading (55% wt/wt). The in vitro drug release was remarkably lower than that from the corresponding physical mixture at both pH 7.5 and pH 7.0. In the latter case, the release was not complete at 24 hours. The kinetic analysis shows the importance of the diffusion through the particle in controlling the drug release rate. The obtained results show that hydrotalcite may be used to prepare modified release formulations.

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well.The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved.

Chitosan and a modified chitosan as agents to improve performances of mucoadhesive vaginal gels.

New mucoadhesive formulations were designed and studied in order to improve local vaginal therapy by increasing formulation retention prolonging thus drug-mucosa contact time. Some gels were prepared using hydroxyethylcellulose (HEC) alone or mixed with chitosan (CS) or its derivative 5-methyl-pyrrolidinone-chitosan (MPCS) and were loaded with the antibacterial metronidazole (MET) (0.75%). All formulations showed pseudoplastic flow and viscosity increase was observed proportionally to chitosan content (CS>MPCS). Prepared gels showed better extrusion properties (yield stress) than market formulation Zidoval. Mucoadhesion force studies permitted to point out that: (i) CS decreases mucoadhesion force; (ii) MPCS addition increases the mucoadhesion force at high percentage; (iii) all gels containing chitosan showed better mucoadhesive performances than Zidoval. Gels containing MPCS showed higher and faster drug release than those containing CS. All the preparations were able to release higher drug amounts if compared to market formulation. In conclusion MPCS improved gel characteristics in terms of mucoadhesion force, rheological behaviour and drug release pointing out that this modified chitosan is very suitable to obtain manageable and more acceptable vaginal formulation.

Ag/AgCl nanoparticle decorated layered double hydroxides: synthesis, characterization and antimicrobial properties

A layered double hydroxide (LDH) surface was employed as a substrate for growing silver nanoparticles (NPs). An efficient method to produce stable silver/silver chloride nanoparticles supported on the ZnAl-LDH surface was developed. NPs of AgCl were grown on the ZnAl-LDH surface by using AgNO3 as the silver source. The ZnAl-LDH in chloride form acts as a nucleating agent, and depending on the pH of the LDH dispersion, AgClNPs with different dimensions were obtained. In particular AgClNPs with a diameter of 60 nm were formed at pH 5. The AgClNPs supported on LDH sheets were partially reduced by different reducing agents (NaBH4 and formaldehyde) resulting in a Ag/AgCl-LDH nanocomposite. The silver chloride and silver NP dimensions were evaluated by X-ray powder diffraction, field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). UV-Vis spectra of the samples upon reduction showed a band centred at 415 nm due to the surface plasmon resonance of silver nanoparticles with a diameter of about 10 nm, in agreement with the TEM analysis. The AgCl-LDH and Ag/AgCl-LDH nanocomposites, subjected to antimicrobial tests, exhibited good antimicrobial activity against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus epidermidis and S. aureus) bacteria and yeast (Candida albicans). The nanocomposites were also studied for their ability to release silver by obtaining release curves, under conditions of antibacterial assays. Finally, the nanocomposites antibacterial behavior, as a function of time, was investigated by performing time-kill experiments using S. aureus and Candida albicans.

FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

Synthesis of some new 1,4-benzothiazine and 1,5-benzothiazepine tricyclic derivatives with structural analogy with TIBO and their screening for anti-HIV activity#

Abstract Several new tricyclic derivatives with structural analogy to TIBO were prepared starting from properly substituted 1,4-benzothiazines and 1,5-benzothiazepine. All synthesized compounds were submitted to screenings for in vitro anti-HIV-1 activity. Only two compounds showed moderate activity.

Use of SBA-15 for furosemide oral delivery enhancement

The objective of this research was to realize a new oral solid dosage form in order to improve the release of furosemide (FURO) in its preferential absorption region. In fact FURO is a drug labeled in class IV of the Biopharmaceutical Classification System (BCS) characterized by low and variable bioavailability due to both low solubility and low permeability and because of its weakly acid nature is preferentially absorbed in the stomach whereas its solubility is hampered. FURO was included in the mesoporous silica material SBA-15 obtaining an inorganic-organic compound fully characterized by: thermogravimetric analysis (TGA), X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR) and nitrogen adsorption-desorption analysis and then submitted to in vitro dissolution. The results showed a remarkable dissolution rate improvement in comparison to the crystalline drug and to the marketed product Lasix®. The inclusion product was also submitted to physical stability studies that revealed the matrix ability to prevent re-organization in crystal nucleus of the drug molecules.

Chitosan films containing mesoporous SBA-15 supported silver nanoparticles for wound dressing

Chitosan films containing mesoporous SBA-15 supported silver nanoparticles (AgNPs) were prepared to be applied as a potential wound dressing material. First SBA-15-silver nanoparticle (SBA-15-Ag) composite materials were prepared by a controlled annealing process without the use of organic solvents and reagents. The SBA-15-AgNPs were characterized in detail by X-ray powder diffraction, field emission scanning electron microscopy and transmission electron microscopy which evidenced the presence of uniformly distributed silver nanostructures inside the silicate pores. UV-vis spectra of the sample showed a band at 430 nm characteristic of the surface plasmon resonance of silver nanoparticles with a diameter below 10 nm and X-ray photoemission spectra confirmed the formation of metal-nanoparticles on the silicate template. Then SBA-15-Ag was used to prepare chitosan films which were characterized in detail. In particular, they showed good hydration properties, water vapor transmission rate and mechanical properties. After hydration films exhibited good antimicrobial activity against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus epidermidis and S. aureus) bacteria.

Effect of gliclazide immobilization into layered double hydroxide on drug release.

This paper deals with a new hydrotalcite-like compound used as a matrix to improve dissolution rate of the poorly water-soluble drug gliclazide and to administer at the same time micro- and oligo-elements useful to improve insulin performance. Gliclazide is a second-generation sulfonylurea compound used in the treatment of type II diabetes mellitus. As a consequence of the poor water solubility, its absorption is limited. Thus, a new hydrotalcite-like compound containing Zinc and Chromium, micronutrients directly involved in the physiology of insulin and in the carbohydrate, lipid and protein metabolism, was synthesized. The gliclazide-hydrotalcite-like clay nanohybrid was prepared via ion-exchange in its nitrate form and was characterized by inductively coupled plasma-optical emission spectrometry and thermogravimetric analysis. The drug loading resulted in 42.9% (w/w). As a consequence of the intercalation, the interlayer distance of the host increased from 0.89 nm (interlayer distance of nitrate form) to 1.5 nm. The intercalation product was submitted to solubility measurements and in vitro dissolution test. A remarkable improvement of the apparent solubility and dissolution rate in comparison to the crystalline drug was observed in acid fluids (pH 1.2 and 3). The presence of chromium and zinc cations was also found in the medium. These results showed that the hybrid nanostructure could represent a promising system to improve drug dissolution rate and to release cations involved in the performance of insulin.