Massimo Setti

Thermal behaviour and dissolution properties of naproxen in combinations with chemically modified ß-Cyclodextrins

AbstractBinary systems of naproxen with statistically-alkylated s-cyclodextrins (methyl, hydroxyethyl and hydroxypropyl derivatives) were investigated for both solid phase characterization (differential scanning calorimetry, X-ray powder diffraction) and dissolution properties (dispersed amount and rotating disc methods). Kneading, coevaporation and colyophilization of the 1:1 (mol/mol) naproxen/methyl s-cyclodextrin combination, as well as colyophilization of analogous combinations of naproxen with hydroxyethyl and hydroxypropyl s-cyclodextrin, led to amorphous products with higher dissolution rates than the corresponding physical mixtures. A conversion of crystalline to amorphous naproxen was also observed by heating the physical mixtures at about 393 K. The amorphous statistically-alkylated s-cyclodextrins, in particular methyl s-cyclodextrin, can be employed as amorphizing agents for crystalline naproxen.

Mineralogical and geochemical characteristics (major, minor, trace elements and REE) of detrital and authigenic clay minerals in a Cenozoic sequence from Ross Sea, Antarctica

Abstract The mineralogy and geochemistry of the clay fraction of Victoria Land Basin (Ross Sea, Antarctica) sediments was investigated, to determine the origin of clay minerals and the features of authigenic smectite. The investigated core (CRP-3) is ~800 m long, mostly of Oligocene age. The clay fraction of the upper sequence consists of mica, chlorite and detrital smectite, while that of the central and lower part is largely made up of authigenic smectite. Authigenic smectites are ditrioctahedral, with a composition close to saponite, while detrital smectites such as Al-Fe beidellites are dioctahedral. Authigenic smectites have no illite mixed layers, show a higher degree of crystallization, higher MgO, Fe2O3, V, Cr, Co, Ni and Sc contents and lower SiO2, Al2 O3, K2O, TiO2, Ba, Rb and Zr contents with respect to detrital clay minerals, and a clear depletion of LREE with respect to HREE. Authigenic smectite formed from the alteration of volcanic materials and clay minerals.

Interaction of naproxen with noncrystalline acetyl β- and acetyl γ-cyclodextrins in the solid and liquid state

Abstract Randomly acetylated, amorphous β-cyclodextrin (AcβCd) and γ-cyclodextrin (AcγCd), having an average substitution degree per anhydroglucose unit, respectively, of 1.1 and 0.95 (∼7.7 acetyl residues per macrocycle), were investigated for their interactions in the solid and liquid state with naproxen (NAP). Differential scanning calorimetry (DSC), supported by X-ray powder diffractometry (XRD), of NAP–AcβCd and NAP–AcγCd blends revealed an apparent decrease in drug crystallinity which was related to a heating-induced solid-state interaction between the drug and each carrier. A solubility of ∼0.40 NAP mass fraction in amorphous AcβCd and amorphous AcγCd at room temperature was determined. Phase-solubility analysis at 25, 37, and 45°C accounted for A L -type inclusion complexation of NAP with AcβCd ( K 1:1,25°C =4.5(4)×10 3 l mol −1 ) and AcγCd ( K 1:1,25°C =0.80(7)×10 3 l mol −1 ) and revealed a solubilizing efficiency of AcβCd toward NAP ∼4 times that of AcγCd. Equimolar drug–carrier combinations prepared from the respective blends by grinding, kneading, coevaporation and freeze-drying were characterized by DSC and XRD and tested for dissolution rate of NAP using the dispersed amount and continuous flow through methods. The best performance in terms of dissolution rate enhancement (∼23 times and ∼10 times the dissolution efficiency of pure drug in the dispersed amount and continuous flow through tests, respectively) was displayed by the NAP–AcβCd colyophilized product.

Thermal behaviour and physicochemical properties of naproxen in mixtures with polyvinylpyrrolidone

The thermal behaviour (DSC, TGA) of naproxen (NAP) and various grades of polyvinylpyrrolidone (PVP; Mr ≈ 10000, 25000, 40000 and 360000), and their mixtures was investigated. A profound modification of the NAP melting peak, observed in the DSC curves of simply blended systems (physical mixtures) with PVP, was attributed to a solid-state interaction. This interaction proved to be influenced by the composition of the mixture, the PVP average molecular weight and the type of manipulation of the sample (grinding, compaction, heating). The high dispersion of NAP within the PVP matrix probably gives rise to the formation of crystalline drug microaggregates (molecular clusters) responsible for the thermal behaviour. The chemical and physical stability (dissolution rate, crystallinity) of NAP was not significantly affected in the mixtures with PVP.

Interaction of naproxen with alpha-cyclodextrin and its noncyclic analog maltohexaose.

AbstractPurpose. To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with α-cyclodextrin (αCd), amorphous αCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution. Methods. NAP-additive physical mixtures at 0.30,0.18, and 0.10 mass fraction of drug were tested, after increasing grinding times, by differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Interaction in aqueous solution was examined by phase-solubility and fluorescence analyses supported by molecular modelling. Results. In the mixtures with each additive the fusion enthalpy per unit mass of NAP decreased and the half width at half maximum of selected X-ray diffraction peaks of NAP increased with the progress of grinding time following the loss of crystallinity of the samples. The mechanical treatment apparently did not affect the chemical integrity of the drug. Particularly active in the equimolar mixture was the best amorphizing agent, M6. Solution studies and molecular modelling confirmed M6 may have the feature of a supermolecule for NAP, which forms a 1:1 pseudo-inclusion complex that was as stable as the true inclusion complex with αCd. Conclusions. The intrinsically amorphous linear analog of αCd might be a potential amorphism-inducing agent and solubilizer for scarcely water soluble drugs.

Contamination level and human health hazard assessment of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in street dust deposited in Mahshahr, southwest of Iran

ABSTRACT Mahshahr has a strategic position and is considered as industrial hub of Iran. Selected heavy metals and polycyclic aromatic hydrocarbons (PAHs) contamination and health risk, and the mineralogical composition of street dust from Mahshahr were investigated. Results indicated that geology is the main determinant of the dust mineralogical composition. Calculated enrichment factor (EF) and principal component analysis (PCA) showed that Pb, Hg, Zn, and Cu accumulations are greatly influenced by anthropogenic sources including traffic and industry. High heavy metals content poses great ecological risk in the study area and exposure doses revealed that ingestion is the main exposure route to street dust, especially for children in residential/commercial areas. It was found that the total amount of PAHs (∑PAHs) varies from 161 to 1996 µg/kg, dominated by four-ring PAHs. Diagnostic ratios and PCA showed that both petrogenic and pyrogenic sources of PAHs in Mahshahr street dust and traffic play important roles in this respect. Furthermore, toxic equivalents and incremental lifetime cancer risk of PAHs in street dust indicated a high potential carcinogenic risk for inhabitants mainly via dermal contact and ingestion pathways particularly for outdoor workers in industrial use scenario. Finally, distribution maps of total hazard index of heavy metals and cancer risk of PAHs indicated the most impacted zones for different groups and use scenarios.

Clay minerals in late Quaternary sediments from the south Chilean margin as indicators of provenance and palaeoclimate

Abstract An investigation of bulk-rock and clay-fraction compositions of two sedimentary cores from southern Chile was performed to evaluate the record of temporal climatic changes during the late Quaternary (11 ky and 30 ky BP). The bulk mineralogy shows an abundance of feldspars, mica and quartz, with lesser chlorite, amphibole and pyroxene, and variable amounts of carbonates. The clay fraction consists of illite, chlorite and scarce smectite. Smectite shows platy morphology, an Al-Fe beidellite chemical composition, and is detrital. Smectite, together with biogenic carbonate, increases in levels diagnostic of warmer phases. Increases in smectite are attributed either to the beginning of chemical weathering, allowed by the glacial retreat, or to ice extension and sea-level variations. Warmer climates also favoured the increase of carbonate productivity. Levels diagnostic of colder phases show a large decrease in carbonate, small amounts of smectite and large amounts of chlorite and mica, as the abundance of glaciers reduced the productivity and prevented chemical weathering.

Characterization of carbamazepine in systems containing a dissolution rate enhancer

Abstract Carbamazepine is an important anti-convulsant drug, characterized by a low water solubility. In order to improve its dissolution rate, drug:polymer systems were prepared using cross-linked polyvinylpyrrolidone (Polyplasdone XL®-10) as dissolution rate enhancer. The systems were obtained by mixing, milling and solvent evaporation. The systems, characterized by improved drug dissolution rate, were studied by: Scanning Electron Microscopy (SEM), X-Ray Diffraction Powder (XRD), and Differential Scanning Calorimetry (DSC).

Kaolinite in pharmaceutics and biomedicine

Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earths crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2μm (if compared to a human red blood cell of a typical diameter 6.2-8.2μm or to a virus particle of about 50nm diameter). The kaolinite platelets, either stacked together with a common booklet-like shape in a highly ordered structure (well crystallized) or disordered structure (poorly crystallized), consist of layers considered as a strong dipole of hydrophobic siloxane surface dominated by negative charges, and the other hydrophilic aluminol surface carries positive charges. Kaolinite has been used in many pharmaceutical applications as excipient or active ingredient, because it exhibits excellent physical, chemical and surface physicochemical properties. In addition to their classical pharmaceutical uses, kaolinite and its derivatives have been recently considered as a promising material in many biomedical innovation areas such as drug, protein and gene delivery based on the high interaction capacities with organic and biochemical molecules, bioadhesion and cellular uptake. Pharmaceutical kaolin grades are considerably demanded for usage as excipient in formulations of solid and semi-solid dosage forms. The most important functionalities of kaolin used as excipient are reported as diluent, binder, disintegrant, pelletizing and granulating, amorphizing, particle film coating, emulsifying and suspending agent. Because of its uninjured bioactivity, kaolinite has been also used as active agent for treatment of some common diseases. It can be topically administered as hemostatic agent, dermatological protector, anti-inflammatory agent and in pelotherapy, or orally as gastrointestinal protector, and antibacterial, antiviral, detoxification or antidiarrheal agent. With these premises, the future of kaolinite in health-care uses is strongly interesting, especially in the development of pharmaceutical and cosmetic industries. In biomedicinal investigations, it can be considered as a promising natural geomaterial for designing new derivatives that can contribute in the trials of discovering new therapeutic systems and treatment pathways of global challenge diseases such as cancer, viruses, antibiotic resistant bacteria, alzheimer, chronic skeletomuscular and geriatric diseases.

Clay mineral assemblages as indicators of hydrothermalism in the basal part of the CRP-3 core (Victoria Land Basin, Antarctica)

Abstract The CRP-3 drilling project collected sediments from 3 to 939 mbsf (metres below sea floor) in the Victoria Land Basin in Antarctica.The upper sequence (down to ~790 m bsf) is of Cenozoic age and made up of detrital glaciogenic sediments; the characteristics of clay minerals in this part have been reported elsewhere.Here, the compositional features of clay minerals in the lower sequence such as conglomerates, Devonian sandstones and dolerites are described and genetic processes clarified.Clay minerals in the deepest part of the sequence derive from the alteration of different lithologies that mostly make up the sedimentary basin. Two clay mineral assemblages were characterized through analysis by X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM).From 790 to 823 mbsf, samples consist of authigenic smectite of variable chemical composition forming imbricated texture of plates or flakes.The smectites probably result from hydrothermal/diagenetic transformation of earlier minerals.The primary smectite cement underwent reorganization during shearing and cataclasis.The lowest part of the sequence (below 823 mbsf) is characterized by an assemblage of kaolinite, mixed-layer illite-smectite, Fe oxyhydroxide, sporadic smectite and poorly crystallized illite.It reflects a stronger alteration process than that recorded in the upper units of core CRP-3, related to hydrothermalism connected with the intrusion of an igneous body.Both assemblages show clear differences in particle morphology, texture and smectite composition to the clay assemblages found in the Cenozoic glaciomarine sediments in the upper sequence.The different phases of alteration appear related to the processes of rifting, exhumation and faulting that characterized this region since the Mesozoic.