Eli Shefter

In Vitro Release Kinetics of Gentamycin from a Sodium Hyaluronate Gel Delivery System Suitable for the Treatment of Peripheral Vestibular Disease

For certain patients who experience intense vertigo arising from unilateral vestibular lesions, the primary therapy is a vestibular nerve section, an intracranial surgical procedure. One alternative to this treatment is therapeutic ablation of vestibular function on the unaffected side using an ototoxic agent. We prepared a biodegradable sustained-release gel delivery system using sodium hyaluronate that can be administered into the middle ear using only a local anesthetic. The gel contains gentamycin sulfate, the ototoxic agent of choice for treatment of unilateral vestibulopathy, and it exhibits diffusion-controlled release of the drug over a period of hours. The released gentamycin could then diffuse into the inner ear through the round membrane. This represents an important advance over previous formulations, which used only gentamycin sulfate solutions, in that it should allow more careful control of the dose, it should reduce loss of the drug from the middle ear site, and it should maintain intimate contact with the round membrane. By carefully controlling the dose, it should be possible to inhibit vestibular function while minimizing hearing loss. Herein we describe the in vitro release kinetics of gentamycin sulfate from sodium hyaluronate gels and find that the system obeys Fickian behavior.

Crystal and Molecular Structure of Acetylselenocholine Iodide

The structure of acetylselenocholine iodide has been determined by x-ray crystallographic analysis. The molecule is in the trans conformation about the C—C bond of the choline residue. This conformation appears to explain the molecules inability to give a positive cholinergic response when added to an electroplax preparation.

A Kinetic Study of the Solid State Transformation of Sodium Bicarbonate to Sodium Carbonate

AbstractThe thermal transformation of sodium bicarbonate to anhydrous sodium carbonate was studied in an open system between 82°C and 95°C by an x-ray powder diffraction method, The kinetic behavior of this transformation for finely ground material can be ascribed to the “diminishing sphere” model (l/3 order). In the transformation process an intermediate state lacking crystallinity was observed. This state is attributed to the formation of numerous surface nuclei of anhydrous sodium carbonate.

Ring-D-bridged steroid analogs. VI. Proof of stereochemistry and further reactions of 14α, 17α-etheno-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate

Abstract Curtius degradation of 14α, 17α-etheno-16α-carboxypregn-5-ene-3β-ol-20-one acetate (IV) to the benzylurethane (V) is described. Selective catalytic reduction of 14α, 17α-etheno-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate (III) afforded 14α, 17α-ethano-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate (VI). Hunsdiecker degradation of the carboxylic acid VIII, derived from VI gave 14α, 17α-ethano-16α-iodopregn-5-ene-3β-ol-20-one acetate (IX). Hydrolysis of IX to the 3β-alcohol X was followed by catalytic reduction to 14α, 17α-ethano-5α-pregnane-3β-ol-20-one (XI). The latter compound was also prepared from 14α, 17α-ethenopregn-5-ene-3β-ol-20-one (XII). The stereochemistry previously assigned to I, on the basis of analogies, has been proved by a combination of chemical and physical evidence, including an x-ray crystal structure determination on IX.

Crystal structure analysis of the desolvation of the chloroform solvate of griseofulvin

Abstract The crystal structures of the chloroform solvate and a non-solvated form of griseofulvin were determined by X-ray diffraction methods. There are substantial differences in the packing arrangements of the two forms. The chloroform molecules in the solvate are arranged in layers perpendicular to the c -axis. This dictates the direction which the solvent can exit from the crystal.

Dissolution behavior of 17β-estradiol (E2) from povidone coprecipitates. comparison with microcrystalline and macrocrystalline E2

Abstract The dissolution rates of macrocrystalline 17β-estradiol (E 2 ), microcrystalline E 2 and E 2 -povidone coprecipitates and physical mixtures varying in weight ratio from 1 : 1 to 1:49 were determined at 37°C. E 2 dissolution from the coprecipitates was markedly faster than that from either macro- or microcrystalline forms of the drug and was found to increase with decreasing E 2 -to-povidone weight ratio. Based on the results of X-ray diffraction, differential scanning calorimetric. Raman spectroicopic, and thermal gravi metric analysis studies, it is concluded that the formation of a more water soluble, high energy state of E 2 is responsible for the increased dissolution rate of this natural cstrogen from low weight ratio povidone coprecipitates. These findings suggest that the use of E 2 -povidone coprecipitates may increase the systemic availability of E 2 .

Hydrolytic behavior of some aluminum antiperspirant materials in acid

Abstract The hydrolysis rates of a series of aluminum chlorohydrate materials in hydrochloric acid solutions were studied using a colorimetric procedure. In acidic solutions, these materials exist as polynuclear hydroxy complexes that hydrolyze to monomeric aluminum species at rates which are related to their aluminum to chlorine ratios (basicity) and the pH of the solution. In general, the slower the observed hydrolytic rate the greater was the atomic ratio of aluminum to chlorine. The fraction of polynuclear aluminum species in aqueous solutions of the compounds varied in accordance with their basicity, increasing as the basicity increases. All the chlorohydrates exhibited similar X-ray diffraction patterns. They were typical of non-crystalline materials.

Crystal and molecular structure of 1,7-dimethylguanosine iodide

The prominent feature of the packing arrangement in 1,7-dimethylguanosine iodine is the sandwiching of the iodine atom by the bases.

STRUCTURAL VARIATIONS IN CHOLINERGIC LIGANDS

Publisher Summary This chapter describes the structural variations in cholinergic ligands. Comparative pharmacological and biochemical studies of chemically modified analogues of a particular chemical entity have been extensively used as an approach for defining the chemical nature of receptors. Rules relating the conformational and electronic requirements necessary for affinity and efficacy of a molecule in a particular receptor can sometimes be developed. The failure to produce significant structure activity relationships for cholinergic agents stems from a number of factors. The chapter reviews the various observations that have been made to date on the structures of pertinent cholinergic ligands. There is no direct evidence on the structure of a molecule at the active site of a cholinergic receptor. It is, thus, necessary to use circumstantial evidence from molecular orbital calculations, and crystallographic and solution studies to learn about the nature of substrate at a receptor site until direct observations of the receptor–substrate complex can be made.

Thermal and photochemical rearrangements, and X-ray crystal structure of a 2-benzazocine derivative

Dimethyl 8-oxo-1-phenyl-12-azatricyclo[7,2,1,02,7]dodeca-2(9),3,5,11-tetraene-10,11-dicarboxylate (4) at 115° in toluene undergoes a novel rearrangement to a benzazocine derivative (5) which undergoes further rearrangement on photolysis; the structure of (5) has been determined by X-ray crystallography.