Giuliano Grandolini

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.

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.

Quantitative analysis of fluoroquinolones by 1H- and 19F-NMR spectroscopy

Abstract 1H- and 19F-NMR assay of pefloxacin (I), norfloxacin (II) and ofloxacin (III) in some pharmaceutical forms has been developed. The method, based on the integration of appropriate signals of both analytes and internal standards, is simple, rapid, precise, and accurate, and can be used for quality control of these drugs.

Studies on annulated 1,4-benzothiazines and 1,5-benzothiazepines. IX. Imidazo [2,1-d][1,5] benzothiazepines: synthesis and in vitro benzodiazepine receptor affinity

Summary The synthesis of three series of 1- and 2-substituted imidazo[2,1-d][1,5]benzothiazepines is accomplished starting from 1,5-benzothiazepin-4-ones. All the synthesized compounds were evaluated for their affinity for the benzodiazepine receptor, testing their ability to displace [3H]Flunitrazepam from bovine brain membrane protein. A few of the tested compounds showed good affinity, in particular compound 9a (Ki = 43.00 nM). The GABA-ratio of the active compounds suggests an antagonist or partial agonist activity. The data obtained allow us to draw some comments on the structure-activity relationships.

Synthesis, antibacterial and antifungal activities of several new benzo- naphtho- and quinolino-1,4-thiazine and 1,5-thiazepine derivatives

Abstract The synthesis of a number of thiosemicarbazone, phenylthiosemicarbazone, oxime and oxime O -ester derivatives of benzo- naphtho- and quinolino-1,4-thiazines and 1,5-thiazepines is described. All the compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 5b, 5d, 5g and 8f showed interesting antifungal activity.

Isolation and structure of a quassinoid from Ailanthus glandulosa

Abstract A new quassinoid, 2-dihydroailanthone, has been isolated from the bark of Ailanthus glandulosa . Its structure was established on the basis of spectroscopic data and chemical evidence.

A new neoquassin derivative from Quassia amara

Abstract A new quassinoid, a dihydronorneoquassin, has been isolated from Quassia amara wood. In addition the known compounds, paraine and isoparaine, were

Anti-inflammatory Plants

Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemicals, or microbiological agents. Inflammation is the body’s effort to inactivate or destroy invading organisms, remove irritants, and set the stage for tissue repair. When healing is complete, the inflammatory process usually subsides.

Microporous material from kanemite for drug inclusion and release

A microporous material obtained from kanemite, a layered polysilicate, was studied in order to investigate its feasibility of including drugs and then releasing them. Diphenydramine hydrochloride was chosen as a model drug. The preparation of the microporous material and its loading with the drug are described. As kanemite is able to intercalate anions between its layers, the intercalation compound of diphenydramine and kanemite was also prepared. Both the drug-loaded microporous material and the intercalation compound were submitted to dissolution tests at pH 7.5. The drug release profiles from these two different materials and from a physical mixture were compared.