Construction and performance characteristics of new ion selective electrodes based on carbon nanotubes for determination of meclofenoxate hydrochloride.

This work offers construction and comparative evaluation the performance characteristics of conventional polymer (I), carbon paste (II) and carbon nanotubes chemically modified carbon paste ion selective electrodes (III) for meclofenoxate hydrochloride are described. These electrodes depend mainly on the incorporation of the ion pair of meclofenoxate hydrochloride with phosphomolybdic acid (PMA) or phosphotungestic acid (PTA). They showed near Nernestian responses over usable concentration range 1.0 × 10(-5) to 1.0 × 10(-2)M with slopes in the range 55.15-59.74 mV(concentrationdecade)(-1). These developed electrodes were fully characterized in terms of their composition, response time, working concentration range, life span, usable pH and temperature range. The electrodes showed a very good selectivity for Meclo with respect to a large number of inorganic cations, sugars and in the presence of the degradation product of the drug (p-chloro phenoxy acetic acid). The standard additions method was applied to the determination of MecloCl in pure solution, pharmaceutical preparations and biological samples. Dissolution testing was also applied using the proposed sensors.

Stability-indicating electrochemical methods for the determination of meclophenoxate hydrochloride and pyritinol dihydrochloride using ion-selective membrane electrodes.

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for the determination of meclophenoxate hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their degradation products are described. The sensors are based on the use of the ion-association complexes of (I) and (II) cation with sodium tetraphenyl borate and ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In addition beta-cyclodextrin (beta-CD) membranes were used in the determination of I and II. These ion pairs and beta-CD were then incorporated as electroactive species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta-cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB), (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73, 51.64 and 54.05 per concentration decade with average recoveries of 99.92+/-1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta-CD respectively. Pyritinol also showed near Nernestian responses over the concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit-RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10 and 32.89 per concentration decade and average recoveries of 99.99+/-0.827, 100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD respectively. The sensors were used successfully for the determination of I and II in laboratory prepared mixtures with their degradation products, in pharmaceutical dosage forms and in plasma.

Chromatographic analysis of 1,3-bis(dimethylamino)isopropyl 4-chlorophenoxyacetate dihydrochloride, a new CNS stimulant.

A reversed-phase liquid chromatographic method is developed for the assay of the new CNS stimulant, 1,3-bis(dimethylamino)isopropyl 4-chlorophenoxyacetate dihydrochloride (BCE-001), and its main contaminant, 4-chlorophenoxyacetic acid (PCPA). In the first place the possible reactions of BCE-001 with mobile phase components are investigated and it is found that BCE-001 is readily hydrolysed in water and undergoes transesterification in methanol or ethanol. The methyl ester is formed rapidly and quantitatively so that BCE-001 can be assayed as methyl 4-chlorophenoxyacetate. PCPA is formed as a result of the hydrolysis of BCE-001 during the sample pretreatment and chromatographic separation and this causes an overestimate of the PCPA impurity in the bulk drug. An effective method is developed to prevent the hydrolysis of BCE-001 during sample pretreatment.

Nonlinear estimation of kinetic parameters for solid-state hydrolysis of water-soluble drugs. II: Rational presentation mode below the critical moisture content.

A logical presentation mode for accelerated data obtained at low relative humidities has been developed. A model is proposed leading to an equation relating the percent decomposition, x, at time t, to the temperature (T, K), and the water vapor (P, mmHg) in an open system. The data presented support the equation.

Nonlinear estimation of kinetic parameters for solid-state hydrolysis of water-soluble drugs.

Nonlinear-regression analysis was applied to estimate the kinetic parameters for the solid-state hydrolysis of meclofenoxate hydrochloride [2-(dimethylamino)ethyl (4-chlorophenoxy)acetate hydrochloride; 1] and propantheline bromide [(2-hydroxyethyl)diisopropylmethylammonium bromide xanthene-9-carboxylate; 2]. The percent decomposed (x) at the initial stage of decomposition was found to conform to the empirical equation x = ktn, where n and k are constants. The goodness of fit of the data was better than with the Prout-Tompkins equation. The parameters indicating the dependence of the rate on temperature (T) and water vapor pressure (P) were estimated by nonlinear-regression analysis based on the equation: x = x0 exp[(Ea/R)(1/298-1/T)] (P/18.167)s(t/50)n, where xo is the percent decomposed at t = 50 d, T = 298 K and P = 18.167 mmHg, and Ea (activation energy), s, and n are constants. For the hydrolysis at a relative humidity (RH) above the critical relative humidity (CRH), nonlinear parameter estimation provided statistically meaningful estimates of Ea, s, x0, and n, and it was suggested that these parameters could be regarded as constants in the experimental range. For the hydrolysis at RH below the CRH, however, the parameters could not be converged by nonlinear-regression analysis, and Ea and/or s were assumed not to be constant in this RH range.