Mechanistic understanding of salt-induced drug encapsulation in nanosuspension via acid-base neutralization as a nanonization platform technology to enhance dissolution rate of pH-dependent poorly water-soluble drugs.

An acid-base neutralization technique has generated interest for the ability to achieve an enhanced dissolution of pH-dependent weakly basic or acidic poorly water-soluble drugs. However, the underlying nanonization mechanism, following acid-base neutralization, requires further elucidation. We hypothesized that the nanosuspensions (NSPs) via nanonization of drug particles could be attributed to the "salt-induced effect" and surfactant-driven micellization after acid-base neutralization. Rebamipide (RBM) and valsartan (VAL) were chosen as model drugs owing to poor water solubility and pH-dependent aqueous solubility. The drug NSP was rapidly obtained via salt formation (NaCl) after neutralization of the drug in basic NaOH solution and poloxamer 407 (POX 407) in acidic HCl solution. The NSP surrounded by NaCl salt was further stabilized by POX 407. The resulting NaCl salt modulated the critical micelle aggregation of POX 407, stabilizing the drug-loaded NSP in a cage of salt and micellar surfactant. In non-assisted homogenization, size analysis indicated the relationship between salt concentration and size reduction. Fourier transform infrared (FTIR) spectra revealed that the existence of hydrogen bonding between the drug and surfactant after neutralization, attributed to NSP size reduction. Changes in drug crystallinity to the nano-amorphous state were confirmed by powder X-ray diffraction (PXRD). Overall, the salt-induced drug NSP synergistically enhanced the dissolution rate, narrowing a gap between drug dissolution profiles in different pH environments.

Comparison of 2 strategies to enhance pyridoclax solubility: Nanoemulsion delivery system versus salt synthesis.

Pyridoclax is an original oligopyridine lead, very promising in treatment of chemoresistant cancers. However, from solubility measurement and permeability evaluation, it appeared that this compound can be considered as a BCS II drug, with a poor water solubility. To overcome this unfavorable property, two strategies were proposed and compared: pyridoclax di-hydrochloride salt synthesis and formulation of pyridoclax-loaded nanoemulsions (PNEs) efficiently performed by transposing the spontaneous emulsification process previously developed by our team. Whereas the salt improved the thermodynamic solubility of the drug by a factor 4, the apparent solubility of the encapsulated pyridoclax was 1000-fold higher. Their stability was assessed upon dilution in various complex biomimetic media relevant for oral administration (SGF, FaSSIF-V2, FeSSIF-V2) or for the intravenous route (PBS). The solubility of the salt was affected by the nature of the medium, indicating that it could precipitate after administration, negatively impacting its bioavailability and its efficiency in vivo. On the contrary, in all media, PNEs remained stable in terms of granulometric properties (determined by DLS), ζ-potential and encapsulation efficiency (measured by HPLC). Thus, such nanomedicines appear as a valuable option to perform preclinical studies on the promising pyridoclax.

Physical-chemical treatment of wastes: a way to close turnover of elements in LSS.

"Man-plants-physical-chemical unit" system designed for space stations or terrestrial ecohabitats to close steady-state mineral, water and gas exchange is proposed. The physical-chemical unit is to mineralize all inedible plant wastes and physiological human wastes (feces, urine, gray water) by electromagnetically activated hydrogen peroxide in an oxidation reactor. The final product is a mineralized solution containing all elements balanced for plants' requirements. The solution has been successfully used in experiments to grow wheat, beans and radish. The solution was reusable: the evaporated moisture was replenished by the phytotron condensate. Sodium salination of plants was precluded by evaporating reactor-mineralized urine to sodium saturation concentration to crystallize out NaCl which can be used as food for the crew. The remaining mineralized product was brought back for nutrition of plants. The gas composition of the reactor comprises O2, N2, CO2, NH3, H2. At the reactor's output hydrogen and oxygen were catalyzed into water, NH3 was converted in a water trap into NH4 and used for nutrition of plants. A special accessory at the reactor's output may produce hydrogen peroxide from intrasystem water and gas which makes possible to close gas loops between LSS components.

Towards the eradication of iodine-deficiency disorders in Brazil through a salt iodination programme.

Iodine-deficiency disorders have been a serious public health problem in Brazil because of the failure of a salt iodination programme established in 1953. The reasons for this failure were logistical, e.g., potassium iodide was not supplied to all salt-producers, iodination of salt was largely erratic, and part of the population at risk used only non-refined salt, which was not iodinated. In 1978 a task force was therefore formed to implement measures to eliminate iodine-deficiency disorders from the country. For this purpose, potassium iodate was distributed, free-of-charge, to all salt mills and an iodate dosing spray was supplied without cost to small salt producers. Also, regional laboratories for determining iodine in salt were set up, inspectors made regular visits to the salt mills, and samples of salt from commerce and from the producers were analysed. More than 90% of the samples contained 10-30 mg iodine per kg. In three typical areas of the country with endemic goitre the urinary excretion of iodine increased from an average of less than 40 mug iodine to 125 +/- 38 mug iodine per g creatinine. In conclusion, the salt iodination programme was a complete success and could serve as a model for other countries with a high prevalence of iodine-deficiency disorders.

[Investigations for obtaining compounds with potential antiinflammatory action, carboxymethylic ethers of some oximes]. / Cercetari privind: obtinerea de compusi cu actiune antiinflamatoare potentiala, eteri carboximetalici ai unor oxime.

In this paper the synthesis of 5 etheric derivates of some aromatic oxymes: p-metoxy-benz-(sin)-aldoxyme, p-chlorine-benz-(sin)-aldoxyme, sin-piperonal-oxyme, 2,4-di- chlorinebenzaldoxyme and 3,4-dichlor-benzaldoxyme were described. In view of a subsequent study on the antiinflammatory action a simple method for obtaining these compounds based on the reaction between the sodium salt of the monochloracetic acid and the sodium derivates of the corresponding oxymes. The structure of the newly obtained products was confirmed by the elementary quantitative chemical analysis and the spectral analysis in IR.