Nanocarriers as Tools in Delivering Active Compounds for Immune System Related Pathologies.

BACKGROUND: Immune system related pathologies affect an increasing number of patients every year, having potentially lethal consequences and requiring expensive and difficult tolerated treatments. This area of pathologies offers an excellent potential for the development of innovative solutions such as nanoformulations; this review aims to describe the main categories of nanostructured drug delivery platforms that have been developed in order to achieve a more effective, low toxic treatment in autoimmune pathologies. METHODS: We conducted a systematic search of peer-reviewed original studies focusing on nanoformulations suitable for use against autoimmune disorders. Each study was evaluated by at least two reviewers who applied inclusion and exclusion criteria in order to establish the quality of the research reported in the selected papers. The systematic screening of the literature also identified the most recent patents issued in the field of inflammatory/autoimmune diseases which were included in the current paper. RESULTS: One hundred ninety-seven bibliographic titles were included in the review of which fifty-three recently published patents. Twenty-one papers were selected to define the interaction between nanoformulations and the immune system triggering either immunosuppression or immunostimulation. Thirty-seven papers outlined the characteristics of liposomal formulations that have been reported as treatment for several autoimmune diseases including multiple sclerosis. Twentythree articles provided data on the main lipid nanoparticles of the first and second generation which may include physiological lipids with low cytotoxicity. Gold nanoparticles were described by thirteen papers which highlighted the advantages of the new hybrid organic-inorganic nanoparticles vs. the classical ionic gold compounds. Polymeric nanoformulations were the subject of fifty-nine papers that described their preparation as well as various advantages in the treatment of inflammatory disorders; dendrimers and polymeric micelles were included in the study. Thirty-three studies were selected to outline the benefits provided by the use of cyclodextrins as carriers for active drugs. The review also identified the possibility of producing combined nanoformulations (e.g. polymer/cyclodextrin, liposome/polymer) thus achieving superior therapeutic results. CONCLUSION: Nanoformulations offer multiple advantages over the classical pharmaceutical formulations, the main ones being the precise targeted therapy with small doses of active drugs, longer circulating time in the bloodstream, and high loading capacity for diagnostic and therapeutic molecules; moreover, the nanoparticles may be functionalized in order to act as nanotheranostics within the larger frame of personalized medicine.

Synthesis and degradation of Schiff bases containing heterocyclic pharmacophore.

This paper reports on the synthesis and characterization of two Schiff bases bearing 1,2,4-triazolic moieties, namely 4H-4-(2-hydroxy-benzylidene-amino)-5-benzyl-3-mercapto-1,2,4-triazole and 4H-4-(4-nitro-benzylidene-amino)-5-benzyl-3-mercapto-1,2,4-triazole using thin layer chromatography, melting interval, elemental analysis, spectroscopy and thermal stability studies.

Thermal behaviour of procaine and benzocaine Part II: compatibility study with some pharmaceutical excipients used in solid dosage forms.

BACKGROUND: The compatibility study of active substances with excipients finds an important role in the domain of pharmaceutical research, being known the fact that final formulation is the one administered to the patient. In order to evaluate the compatibility between active substance and excipients, different analytical techniques can be used, based on their accuracy, reproducibility and fastness. RESULTS: Compatibility study of two well-known active substances, procaine and benzocaine, with four commonly used excipients, was carried out employing thermal analysis (TG/DTG/HF) and Fourier Transform Infrared Spectroscopy (UATR-FT-IR). The selected excipients were microcrystalline cellulose, lactose monohydrate, magnesium stearate and talc. Equal proportion of active substance and excipients (w/w) was utilized in the interaction study. The absolute value of the difference between the melting point peak of active substances and the one corresponding for the active substances in the analysed mixture, as well the absolute value of the difference between the enthalpy of the pure active ingredient melting peak and that of its melting peak in the different analysed mixtures were chosen as indexes of the drug-excipient interaction degree. All the results obtained through thermal analysis were also sustained by FT-IR spectroscopy. CONCLUSIONS: The corroboration of data obtained by thermal analysis with the ones from FT-IR spectroscopy indicated that no interaction occurs between procaine and benzocaine, with microcrystalline cellulose and talc, as well for the benzocaine-lactose mixture. Interactions were confirmed between procaine and benzocaine respectively and magnesium stearate, and for procaine and lactose.

Physico-chemical solid-state characterization of pharmaceutical pyrazolones: an unexpected thermal behaviour.

In this work, the thermal behaviour of three active substances (phenazone, aminophenazone, phenylbutazone) was studied by drawing up the TG/DTG/DTA curves in air/nitrogen atmosphere at 10 °C min(-1) heating rate. The information on the thermal-induced events was corroborated with the IR spectra of the solid samples (pharmaceutical compounds and the remaining chars after heating treatment), respectively with the ones obtained by evolved gases analysis (EGA). The data on a possible drug-excipient interaction were obtained from the thermoanalytical study of mixtures of these active compounds with talc, magnesium stearate, starch and microcrystalline cellulose. No changes were observed by TG/DTG/DTA curves of mixtures in comparison with the pure compound. Even if the three active substances contain the same heterocyclic ring, having similar molecular structures, their thermal behaviour is not similar. According to thermal and evolved gas analysis, it was proved that formation of CO2 does not involve atmospheric oxygen. By stoichiometric means, the molecular breakdown of aminophenazone can generate only carbon monoxide, which undergoes disproportionation, generating CO2.

Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data.

BACKGROUND: The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. RESULTS: The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin's decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one.The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy's values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). CONCLUSION: The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.

Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms.

Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques were used for assessing the compatibility between ketoprofen (KT) and several excipients as: corn starch, microcrystalline cellulose (PH 101 and PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone K30, magnesium stearate and talc, commonly used in the pharmaceutical form. In order to investigate the possible interactions between the components, the thermal curves of KT and each selected excipients were compared with those of their 1:1 (w/w) physical mixtures. For KT, the DSC curves have shown a sharp endothermic peak at 96.8 °C which corresponds to the melting process (literature value: 94-97 °C), respectively the TG curves demonstrated a simple stage of mass loss in the temperature range of 235-400 °C. FT-IR spectroscopy and X-ray powder diffraction (XRPD) were used as complementary techniques to adequately implement and assist in interpretation of the DSC results. On the basis of thermal results, a possible interaction was found between the KT with polyvinylpyrrolidone K30 and magnesium stearate, which could influence the stability of the KT in the binary mixtures. These possible incompatibilities were confirmed by FT-IR and X-ray analysis.