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

Binary systems of naproxen with statistically-alkylated fcyclodextrins (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 fcyclodextrin combination, as well as colyophilization of analogous combinations of naproxen with hydroxyethyl and hydroxypropyl fcyclodextrin, 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 fcyclodextrins, in particular methyl fcyclodextrin, can be employed as amorphizing agents for crystalline naproxen

Physical characterization of picotamide monohydrate and anhydrous picotamide

Picotamide is an antiplatelet agent given by mouth as monohydrate (PICOW) (Plactidil) in thrombo-embolic disorders. This study deals with physical characterization of PICOW recrystallized from various solvents and the respective dehydration products using X-ray powder diffractometry (XRD), infrared spectroscopy (IR), and thermal analytical techniques (differential scanning calorimetry, DSC; thermogravimetric analysis, TGA; simultaneous TGA/DSC; hot stage microscopy, HSM). Monophasic and biphasic DSC and TGA profiles of water loss were recorded under open conditions for PICOW samples which showed the same monoclinic crystal structure. Biphasic profiles became monophasic for gently ground samples which were, however, structurally identical to the intact samples. Morphological factors, the various degree of “perfection” of the PICOW crystal lattice, and/or cluster aggregation of PICOW crystals were assumed to be responsible for the differing dehydration patterns. Polymorphism in anhydrous picotamide, i.e., nucleation of crystal forms A, mp 135.5 ± 0.4 °C, and B, mp 152.9 ± 0.3 °C after dehydration of PICOW, was detected by DSC and HSM. The dehydration product of PICOW under isothermal conditions (115 °C, 20 mmHg), PICOA, was mainly composed of the lower melting polymorph A (fusion enthalpy 74.4 ± 2.2 J g-1), which gradually reverted to the starting hydrate by storing in an ambient atmosphere. Dissolution tests of PICOW and PICOA in water at 37 °C as both powders and compressed disks reflected to some extent the higher solubility of the metastable form (by 24% at 37 °C) in terms of both higher dissolution efficiency and percent of active ingredient dissolved (by 28%) and intrinsic dissolution rate (by 32%)

Concentrations and trophic interactions of novel brominated flame retardants, HBCD, and PBDEs in zooplankton and fish from Lake Maggiore (Northern Italy)

Following the release of the international regulations on PBDEs and HBCD, the aim of this study is to evaluate the concentrations of novel brominated flame retardants (NBFRs), including 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), decabromodiphenyl ethane (DBDPE), hexabromobenzene (HBB), and pentabromoethylbenzene (PBEB), in an Italian subalpine lake located in a populated and industrial area. The study investigated specifically the potential BFR biomagnification in a particular lake's pelagic food web, whose structure and dynamics were evaluated using the Stable Isotope Analysis. The potential BFR biomagnification was investigated by using the trophic-level adjusted BMFs and Trophic Magnification Factors (TMFs), confirming that HBCD and some PBDE congeners are able to biomagnify within food webs. Comparing the calculated values of BMFTL and TMF, a significant positive correlation was observed between the two factors, suggesting that the use of BMFTL to investigate the biomagnification potential of organic chemical compounds might be an appropriate approach when a simple food web is considered

Interaction of naproxen with noncrystalline acetyl beta- and acetyl gamma-cyclodextrins in the solid and liquid state.

Randomly acetylated, amorphous beta-cyclodextrin (AcbetaCd) and gamma-cyclodextrin (AcgammaCd), having an average substitution degree per anhydroglucose unit, respectively, of 1.1 and 0.95 (about 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–AcbetaCd and NAP–AcgammaCd 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 about 0.40 NAP mass fraction in amorphous AcbetaCd and amorphous AcgammaCd at room temperature was determined. Phase-solubility analysis at 25, 37, and 45°C accounted for AL-type inclusion complexation of NAP with AcbetaCd and AcgammaCd and revealed a solubilizing efficiency of AcbetaCd toward NAP about 4 times that of AcgammaCd. 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 (about 23 times and about 10 times the dissolution efficiency of pure drug in the dispersed amount and continuous flow through tests, respectively) was displayed by the NAP–AcbetaCd colyophilized product