Stability studies of alprazolam tablets: effects of chemical interactions with some excipients in pharmaceutical solid preparations

An HPLC method was developed to determine the stability of alprazolam (AL) as a pure drug and in monodrug pharmaceutical tablets. The main degradation product of AL tablets was isolated and fully characterized as triazolaminoquinoleine (TAQ). For a quantitative evaluation of the excipient effects in the pharmaceutical formulations, a 2^k fractionated factorial design was applied in the preparation of the different samples. The kinetic of degradation of AL in each formulation was followed by UV spectrophotometry. It was found that excipients like CMC and magnesium stearate favour degradation, while the rate of the reaction is decreased when lactose and starch were used as excipients. A mechanism for the interactions of AL with some excipients is postulated that explains the observed results. Copyright © 2009 John Wiley & Sons, Ltd.     

New direct 11B NMR-based analysis of organoboranes through their potassium borohydrides

Representative organoborane mixtures were quantitatively converted to their borohydrides through their reaction with activated KH (KH), permitting their detailed analysis by (11)B NMR. Through the treatment of commercial KH with a THF solution of lithium aluminum hydride (LAH), a dramatic change in the surface morphology results as revealed by scanning electron microscopy (SEM). Energy dispersed spectroscopy (EDS) was employed to reveal that the LAH treatment deposits a significant amount of an unknown aluminum-containing species on the surface of the KH, which imparts a unique reactivity to the KH. Even highly hindered organoboranes are quantitatively converted to their borohydrides by replacing electronegative groups (e.g., OR, halogen) with hydrogen, retaining only the carbon ligation. Through this simple KH treatment, complex organoborane reaction mixtures are converted to the corresponding borohydrides whose (11)B NMR spectra normally exhibit resolved signals for the individual species present. The integration of these signals provides quantitative information on the relative amounts of each component of the mixture. New generalities for the effect of alpha-, beta-, and gamma-substituents have also been determined that provide a new, simple technique for the determination of the isomeric distribution in organoborane mixtures resulting from common organoborane processes (e.g., hydroboration). Moreover, the (1)H-coupled (11)B NMR spectra of these mixtures reveal the extent of alkylation for each species present. Representative organoboranes were examined by this new technique permitting a simple and convenient quantitative analysis of the regio- and diastereomeric composition of a variety of asymmetric organoborane processes. Previously unknown details of pinene-based hydroborations and reductions are revealed for the first time employing the KH (11)B NMR technique.     

Kinetics of dehydroxylation and evaluation of the crystallinity of kaolinite

This study presents results on the kinetics of kaolinite dehydroxylation. The accuracy of various methods of determining the values for the kinetic parameters and their sensitivity in detecting the mechanism of reaction is investigated. In particular, the differential order of reaction method of Baker, the general method of Achar et al., the integral method of Boy and Bohme, and the method of Coats and Redfern as modified by Fong and Chen are considered.

Kaolinites from well-known sources are used to study the influence of crystallinity on the values of kinetic parameters. The statistical significance of the various mathematical methods for the assessment of the data obtained from non-isothermal thermogravimetry is determined by comparison with experimental and theoretical data using a computer programme developed for this purpose. The study demonstrates that the kinetic parameters can be used to quantify the degree of crystallinity of kaolinite and also confirms other findings that the dehydroxylation of kaolinite is a second-order reaction.     

A multicommuted flow system for the determination of copper, chromium, iron and lead in lubricating oils with detection by flame AAS

In this work, a flow analysis procedure for the determination of copper, chromium, iron and lead in lubricating oils using flame AAS as detection technique is described. The flow manifold was designed to implement the multicommutation approach and it comprised three 3-way solenoid valves controlled by a personal computer. The flow system presented allowed to process the oil samples to determine wear metals without any prior preparation. Aiming to assess accuracy the results were compared with those obtained by manual procedure using flame AAS. Applying the joint-confidence ellipse test, no significant difference at the 95% confidence level was observed. Other profitable features such as a sample throughput of 50 determinations per hour; relative standard deviations (n = 5) below 2% for Cu, and below 8% for Cr, Fe and Pb; and linear responses in the range 0–40 ppm (w/w) (Cu, Fe) and 0–15 ppm (w/w) (Cr, Pb) were also achieved.     

Adsorption of 3-mercaptopropyltrimethoxysilane and 3-aminopropyltrimethoxysilane at platinum electrodes

In this work we studied the self-assembled monolayer (SAM) formation of 3-mercaptopropyltrimethoxysilane [HS(CH₂)₃Si(OCH₃)₃] (MPS) and 3-aminopropyltrimethoxysilane [H₂N(CH₂)₃Si(OCH₃)₃] (APS) on platinum surfaces. We used X-ray photoelectron spectroscopy (XPS), specular reflectance FTIR, and electrochemistry to study the composition and structure of the self-assembly. XPS results of the Pt modified electrodes showed the presence of sulfur and nitrogen binding energy peaks indicating the presence of MPS and APS. The platinum substrates modified with MPS and APS showed IR absorption bands corresponding to the different stretches present in both compounds. Platinum disk electrodes, before and after being submerged in 1 mM solutions of MPS and APS for 24 h, were characterized voltammetrically by using 2.5 mM K₄Fe(CN)₆ in 0.1 M KCl, as the redox active couple. The MPS/Pt system is free of mass transfer effects, which are characteristic of pinhole defects in an MPS monolayer.     

Optimization and Validation of a Fast Liquid Gradient for Determination of Prominent Flavan‐3‐ols and Flavonols in Fresh Vegetables

A fast high‐performance liquid chromatography method was used for analysis of prominent flavan‐3‐ols and flavonols in vegetables. Gradient elution with phosphoric acid‐acetonitrile mixtures and phosphoric acid‐methanol mixtures allowed fast and complete separation of the studied phenolic compounds within analysis times less than 10 min. The development of two elution gradients using methanol and acetonitrile as modifiers proved to be an excellent approach for the verification of the real polyphenolic composition in vegetables samples because the two optimized methods allowed the separation of the same number of compounds in the same elution order. Diode‐array detection was employed for the provisional identification of phenolic compounds that were not available as standards. We preferred methanol as a modifier because it was less toxic and cheaper than acetonitrile. Detection limits ranged between 0.12 and 0.59 μg mL^–1. High recoveries of phenolics from fresh vegetables were measured in all studied cases, independent of the phenolic structure, matrix, and vegetable in question. High levels of procyanidins between 150 and 450 mg kg^–1 were found in all studied vegetables. Quantification of quercetin and kaempferol glycosides was only possible in marrow and onion, respectively.     

Structure-reactivity correlation in the reactions of pyrrolidine with O-ethyl S-aryl dithiocarbonates in aqueous ethanol

The reactions of pyrrolidine with O-ethyl S-(X-phenyl) dithiocarbonates (X = 4-methyl, 4-methoxy, H, 4-chloro, 4-nitro, 2,4-dinitro, and 2,4,6-trinitro) are subjected to a kinetic study in 44 wt% aqueous ethanol, 25.0°C, and ionic strength 0.2 M (maintained with KCl). Pseudo-first-order kinetics are found under amine excess. Linear plots of the pseudo-first-order rate coefficient against concentration of free-base pyrrolidine are obtained for all the reactions, the nucleophilic rate coefficient (k_N) being the slope of such plots. The Bronsted-type plot (log k_N vs. pK_a for the leaving group) is linear with slope β_lg = − 0.2, which is consistent with a mechanism through a tetrahedral intermediate (T^±) where its formation is rate determining. The β_lg value is very similar to that found in the same reactions in water. There is a great difference in the mechanism of the reactions of O-ethyl S-phenyl dithiocarbonate with pyrrolidine (order one in amine) and piperidine (complex order in amine) in aqueous ethanol, and this is attributed to a greater nucleofugality from T^± of piperidine rather than pyrrolidine. © 1997 John Wiley & Sons, Inc.     

Pentastrontium Tris[tetraoxovanadate(V)] catena‐Monoxocuprate(I), Sr5(VO4)3(CuO) – An Apatite Derivative with Inserted Linear 1Ë[CuO]1– Chains

Sr₅(VO₄)₃(CuO) was prepared via solid state reactions from mixed powders of the metal oxides or carbonates in corundum crucibles in air (1173–1740 K). The compound is transparent and stable in air. The color changes with the preparation temperature from light gray (1173 K) to gray (1740 K). The crystal structure (space group P6₃/m, No. 176; Z = 2; a = 10.126 Å, c = 7.415 Å) is a derivative of the apatite Ca₅(PO₄)₃OH, and is characterized by isolated [VO₄]^3– anions (d(V–O) = 1.710 Å) and infinite linear ^1∞[CuO]^1– chains (d(Cu–O) = 1.854 Å) inserted in the channels parallel to the hexagonal axis. The compound prepared at 1740 K contains vacancies at the copper and oxygen positions of the linear chains (about 10% and 5%, respectively).     

Development and implementation of the k0-standardization and other parametric methods of INAA in Cuba. Part I

This paper explains chronologically the implementation of thek ₀-standardization and other parametric methods in Cuba. Fundamental and applied results in the determination of the most important parameters are obtained, using the IBR-2 at Dubna and Triga Mark III at Mexico reactor facilities. Some modifications in the Stoughton-Halpering convention, and its comparison with the modified Westcott and Høgdahl method are presented. The application of the described methods at the CS-ISCTN low flux facility, using the big samples techniques, is presented.     

Promotion of 1,3-dithiolanes using a bentonitic clay as catalyst

The reactions between 1,2-ethandithiol with several carbonylic compounds to form the corresponding 1,3-dithiolanes were performed using a natural clay as promotor. The target molecules are used as reagents to obtain fine chemicals, herbicides, fungicides, and pharmaceutical compounds among others applications. A kinetic study of camphorquinone and 1,2-ethandithiol showed a first-order dependence with 1,2-ethandithiol as well as with camphorquinone. The substrate transformation in percent was found to be dependent with the reaction time, the amount of catalyst, and the reagents concentration. © 2003 Wiley Periodicals, Inc. 15:71–76, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10215