Beitrage zur Kenntnis substituirter Guanidine und Sulfocarbamide sowie ueber die Einwirkung von Succinylchlorid auf Carbanilid.

Thesis (doctoral)--Universitat Gottingen.

(Table II, page 668-669) Distribution of elements between minerals soluble in 1M Hydroxylamine hydrochloride (Reducible); in 1m HCL (Acid-soluble) and in the insoluble residue of manganese nodules

Attempts to classify pelagic sediments have been based either on appearance and composition, or on the ultimate origin of the components. In particular it appears feasible to distinguish minerals which crystallized in sea-water from those which formed in magmas, in hydrothermal solution, or by weathering under acidic conditions. It is the case of iron and manganese oxide mineral aggregates which constitute one of the major types of rock encountered on the ocean floor; according to Menard (unpublished) about 10% of the pelagic area of the Pacific is covered by such nodules. The nodules consist of intimately intergrown crystallites of different minerals among those identified, besides detrital minerals and organic matter, are opal, goethite, rutile, anatase, barite, nontronite, and at least three manganese oxide minerals of major importance. Arrhenius and Korkisch (1959) have attempted to separate from each other the different minerals constituting the nodules, in order to establish the details of their structure and the localization of the heavy metal ions. The results demonstrate (Table II) that copper and nickel are concentrated in the manganese oxide phases concentrated in the reducible fraction. Cobalt, part of the nickel and most of the chromium are distributed between these and the acid-soluble group of the non-manganese minerals, dominated by goethite and disordered FeOOH.

Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery

The combination of metformin hydrochloride (MTF) and glipizide (GLZ) is second-line medication for diabetes mellitus type 2 (DMT2). In the present study, elementary osmotic pump(EOP)tablet is designed to deliver the combination of MTF and GLZ in a sustained and synchronized manner. By analyzing different variables of the formulation, sodium hydrogen carbonate is introduced as pH modifier to improve the release of GLZ, while ethyl cellulose acts as release retardant to reduce the burst release phase of MTF. A two factor, three level face-centered central composite design (FCCD) is applied to investigate the impact of different factors on drug release profile. Compared with conventional tablets, the elementary osmotic pump (EOP) tablet demonstrates a controlled release behavior with relative bioavailability of 99.2% for MTF and 99.3% for GLZ. Data also shows EOP tablet is able to release MTF and GLZ in a synchronized and sustained manner both in vitro and in vivo

Bioadhesive drug delivery system of diltiazem hydrochloride for improved bioavailability in cardiac therapy

Purpose: To prepare and evaluate bioadhesive buccal films of diltiazem hydrochloride (a L-type calcium channel blocker) for overcoming the limitations of frequent dosing, low bioavailability and gastrointestinal discomfort of oral delivery. Methods: Buccal films were prepared by solvent casting technique using sodium carboxymethylcellulose, polyvinyl pyrrolidone K-30 and polyvinyl alcohol. The films were evaluated for weight, thickness, surface pH, swelling index, in vitro residence time, folding endurance, in vitro release, ex-vivo permeation (across porcine buccal mucosa) and drug content uniformity. Results: The drug content of the formulations was uniform with a range of 18.94 ± 0.066 (F2) to 20.08 ± 0.07 mg per unit film (F1). The films exhibited controlled release ranging from 58.76 ± 1.62 to 91.45 ± 1.02 % over a period > 6 h. The films containing 20 mg diltiazem hydrochloride, polyvinyl alcohol (10 %) and polyvinyl pyrrolidone (1 % w/v) i.e. formulation F5, showed moderate swelling, convenient residence time and promising drug release, and thus can be selected for further development of a buccal film for potential therapeutic uses. Conclusion: The developed formulation is a potential bioadhesive buccal system for delivering diltiazem directly to systemic circulation, circumventing first-pass metabolism, avoiding gastric discomfort and improving bioavailability at a minimal dose.

In vitro effects of Pilocarpus microphyllus extracts and pilocarpine hydrochloride on Rhipicephalus (Boophilus) microplus.

The aim of this study was to assess the activity of aqueous (AE) and ethanolic extracts (EE) and pilocarpine hydrochloride, which were extracted and isolated from Pilocarpus microphyllus (Jaborandi), respectively, on Rhipicephalus (Boophilus) microplus. High performance liquid chromatography (HPLC) was performed to quantify these compounds. Larval packet and adult immersion tests were conducted with different concentrations. Five AE and EE concentrations, ranging from 6.2 to 100.0 mg mL?1, and six concentrations of pilocarpine hydrochloride, ranging from 0.7 to 24.0 mg mL?1, were tested. The lethal concentration (LC50) of each extract for larvae and engorged females was calculated through Probit analysis. The concentration of pilocarpine hydrochloride obtained from the EE and the AE was 1.3 and 0.3% (m/m), respectively. Pilocarpine hydrochloride presented the highest acaricidal activity on larvae (LC50 2.6 mg mL?1) and engorged females (LC50 11.8 mg mL?1) of R.(B.) microplus, followed by the EE which presented LC50 of 56.4 and 15.9 mg mL?1, for larvae and engorged females, respectively. Such results indicate that pilocarpine hydrochloride has acaricidal activity, and may be the primary compound responsible for this activity by P. microphyllus EE.

Guanidinium quinoline-2-carboxylate

In the structure of the guanidinium salt of quinaldic acid, CH6N3+ C10H6NO2-, the asymmetric unit contains two independent cations and anions having similar inter-species hydrogen-bonding environments which include cyclic R2/2(8), R1/2(6) and R2/1(5) associations. These and additional weak aromatic ring pi-pi interactions [minimum ring centroid separation, 3.6621(16)A] give a two-dimensional layered structure.

Guanidinium 3-nitrobenzoate

The structure of title compound, the anhydrous guanidinium salt, CH6N3+ C7H4NO4- shows a three-dimensional structure in which the guanidinium cation is involved in three cyclic R1/2(6) hydrogen-bonding associations with separate carboxylate O-acceptors. Further peripheral associations include a cyclic R2/1(4)cation--anion interaction, forming inter-linked undulating sheets in the framework structure.

Guanidinium 2-phenylacetate

In the structure of CH6N3+ C8H7O2-, the guanidinium cation gives three cyclic hydrogen-bonding interactions with O acceptors of three independent phenylacetate anions, one R2/2(8) and two R1/2(6), giving one-dimensional columnar structures which extend down the 4~2~ axis in the tetragonal cell. Within these structures there are 86.5A^3^ solvent accessible voids.

Three-dimensional hydrogen-bonded structures in the guanidinium salts of the monocyclic dicarboxylic acids rac-trans-cyclohexane-1,2-dicarboxylic acid (2:1, anhydrous), isophthalic acid (1:1, monohydrate) and terephthalic acid (2:1, trihydrate).

The structures of bis(guanidinium)rac-trans-cyclohexane-1,2-dicarboxylate, 2(CH6N3+) C8H10O4- (I), guanidinium 3-carboxybenzoate monohydrate CH6N3+ C8H5O4- . H2O (II) and bis(guanidinium) benzene-1,4-dicarboxylate trihydrate, 2(CH6N3+) C8H4O4^2- . 3H2O (III) have been determined and the hydrogen bonding in each examined. All three compounds form three-dimensional hydrogen-bonded framework structures. In anhydrous (I), both guanidinium cations give classic cyclic R2/2(8) N--H...O,O'(carboxyl) and asymmetric cyclic R1/2(6) hydrogen-bonding interactions while one cation gives an unusual enlarged cyclic interaction with O acceptors of separate ortho-related carboxyl groups [graph set R2/2(11)]. Cations and anions also associate across inversion centres giving cyclic R2/4(8) motifs. In the 1:1 guanidinium salt (II), the cation gives two separate cyclic R1/2(6) interactions, one with a carboxyl O-acceptor, the other with the water molecule of solvation. The structure is unusual in that both carboxyl groups give short inter-anion O...H...O contacts, one across a crystallographic inversion centre [2.483(2)\%A], the other about a two-fold axis of rotation [2.462(2)\%A] with a half-occupancy hydrogen delocalized on the symmetry element in each. The water molecule links the cation--anion ribbon structures into a three-dimensional framework. In (III), the repeating molecular unit comprises a benzene-1,4-dicarboxylate dianion which lies across a crystallographic inversion centre, two guanidinium cations and two water molecules of solvation (each set related by two-fold rotational symmetry), and a single water molecule which lies on a two-fold axis. Each guanidinium cation gives three types of cyclic interactions with the dianions: one R^1^~2~(6), the others R2/3(8) and R3/3(10) (both of these involving the water molecules), giving a three-dimensional structure through bridges down the b cell direction. The water molecule at the general site also forms an unusual cyclic R2/2(4) homodimeric association across an inversion centre [O--H...O, 2.875(2)\%A]. The work described here provides further examples of the common cyclic guanidinium cation...carboxylate anion hydrogen-bonding associations as well as featuring other less common cyclic motifs.

Non-invasive, quantitative analysis of drug mixtures in containers using spatially offset Raman spectroscopy (SORS) and multivariate statistical analysis

In this paper, spatially offset Raman spectroscopy (SORS) is demonstrated for non-invasively investigating the composition of drug mixtures inside an opaque plastic container. The mixtures consisted of three components including a target drug (acetaminophen or phenylephrine hydrochloride) and two diluents (glucose and caffeine). The target drug concentrations ranged from 5% to 100%. After conducting SORS analysis to ascertain the Raman spectra of the concealed mixtures, principal component analysis (PCA) was performed on the SORS spectra to reveal trends within the data. Partial least squares (PLS) regression was used to construct models that predicted the concentration of each target drug, in the presence of the other two diluents. The PLS models were able to predict the concentration of acetaminophen in the validation samples with a root-mean-square error of prediction (RMSEP) of 3.8% and the concentration of phenylephrine hydrochloride with an RMSEP of 4.6%. This work demonstrates the potential of SORS, used in conjunction with multivariate statistical techniques, to perform non-invasive, quantitative analysis on mixtures inside opaque containers. This has applications for pharmaceutical analysis, such as monitoring the degradation of pharmaceutical products on the shelf, in forensic investigations of counterfeit drugs, and for the analysis of illicit drug mixtures which may contain multiple components.

High-resolution imaging of ordered mixed-layer clays

HRTEM has been used to examine illite/smectite from the Mancos shale, rectorite from Garland County, Arkansas; illite from Silver Hill, Montana; Na-smectite from Crook County, Wyoming; corrensite from Packwood, Washington; and diagenetic chlorite from the Tuscaloosa formation. Thin specimens were prepared by ion milling, ultra-microtome sectioning and/or grain dispersal on a porous carbon substrate. Some smectite-bearing clays were also examined after intercalation with dodecylamine hydrochloride (DH). Intercalation of smectite with DH proved to be a reliable method of HRTEM imaging of expanded smectite, d(001) 16 A which could then be distinguished from unexpanded illite, d(001) 10 A. Lattice fringes of basal spacings of DH-intercalated rectorite and illite/smectite showed 26 A periodicity. These data support XRD studies which suggest that these samples are ordered, interstratified varieties of illite and smectite. The ion-thinned, unexpanded corrensite sample showed discrete crystallites containing 10 A and 14 A basal spacings corresponding with collapsed smectite and chlorite, respectively. Regions containing disordered layers of chlorite and smectite were also noted. Crystallites containing regular alternations of smectite and chlorite were not common. These HRTEM observations of corrensite did not corroborate XRD data. Particle sizes parallel to the c axis ranged widely for each sample studied, and many particles showed basal dimensions equivalent to > five layers. -J.M.H.

Improved adhesion of active electrode materials to metal electrode substrates

A battery electrode for a lithium ion battery comprising an elec. conductive substrate having an electrode layer applied thereto, characterized in that the electrode layer includes an org. material having high alky., or an org. material which can be dissolved in org. solvents, or an org. material having an imide group(s) and aminoacetal group(s), or an org. material that chelates with or bonds with a metal substrate or that chelates with or bonds with an active material in the electrode layer. The org. material may be guanidine carbonate. [on SciFinder(R)]