Showing papers in "Journal of the American Pharmaceutical Association in 1952"
TL;DR: The results indicate a low order of toxicity of quercetin and quercitrin as judged by growth, amount of food consumed, hematological findings, organ weights, and microscopical examination of stained section of visceral organs.
Abstract: Data are given on the toxicity of quercetin and quercitrin after intravenous administration in rabbits and rats after oral ingestion of diets containing as much as 1 per cent of quercetin or quercitrin for approximately 410 days. The results indicate a low order of toxicity as judged by growth, amount of food consumed, hematological findings, organ weights, and microscopical examination of stained section of visceral organs.
82 citations
TL;DR: Approximate solubility of rutin in common solvents and solvent‐water mixtures has been determined at room temperature and near boiling temperatures and data are presented showing the formation of r Rutin solvent complexes.
Abstract: Approximate solubility of rutin in common solvents and solvent‐water mixtures has been determined at room temperature and near boiling temperatures. Data are presented showing the formation of rutin solvent complexes. Rutin of high purity, free of quercetin and other flavonoids, has been prepared using this principle. Values for the optical rotation of rutin in various solvents and water‐solvent mixtures are given.
35 citations
32 citations
29 citations
TL;DR: Tentative methods for determining tablet density, bulk density of the mixed ingredients, porosity and pore size of tablets, and the compressional force and compressional work necessary for formation of tablets have been developed.
Abstract: A preliminary report surveying a series of basic studies on compressed tablets is presented. For procurement of data toward elucidation of tablet structure and behavior, tentative methods for determining (a)tablet density, (b) bulk density of the mixed ingredients, (c) porosity and pore size of tablets, and (d) the compressional force and compressional work necessary for formation of tablets have been developed. Other methods for obtaining additional dynamic and static information related to formation of tablets are also discussed. No attempt is made at this time, however, to correlate the data obtained with tablet performance.
29 citations
TL;DR: It has been shown that the body temperature-increasing effect of d-amphetamine as well as d-desoxyephedrine (methamphetamine) is less after repeated daily injections.
Abstract: It has been shown that the body temperature-increasing effect of d-amphetamine as well as d-desoxyephedrine (methamphetamine) is less after repeated daily injections. No significant difference was noted between the reactions toward these two drugs.
27 citations
TL;DR: Tissue reactions at the site of subcutaneous and intramuscular injections of undiluted polyethylene glycol 300, propylene glycol, and peanut oil indicate that a clinical trial of the polyethylenes glycols as vehicles for certain drugs administered parenterally is justified.
Abstract: Tissue reactions at the site of subcutaneous and intramuscular injections of undiluted polyethylene glycol 300, propylene glycol, and peanut oil have been compared. The results obtained and described in this report indicate that a clinical trial of the polyethylene glycols as vehicles for certain drugs administered parenterally is justified.
27 citations
TL;DR: A rapid method for the determination of organic bound iodine is described using chloric acid as the oxidizing digestion reagent and makes possible the analysis of 20 samples per day per analyst.
Abstract: A rapid method for the determination of organic bound iodine is described using chloric acid as the oxidizing digestion reagent. The iodine concentration which may be determined with analytical accuracy ranges from a fraction of a milligram to 100 mg. The method permits the simultaneous estimation of organic bound iodine in several samples since a minimum of care is indicated in the digestion process. No special apparatus is required other than that found in the ordinary laboratory. The procedure makes possible the analysis of 20 samples per day per analyst.
22 citations
TL;DR: As a part of a study of the behavior of pharmaceuticals in solution, the reaction between benzoic acid and caffeine to form a complex was investigated.
Abstract: As a part of a study of the behavior of pharmaceuticals in solution, the reaction between benzoic acid and caffeine to form a complex was investigated. Experimental data were obtained supporting the existence of the complex in solution and the equilibrium constant for the reaction was determined.
20 citations
TL;DR: The products of the riboflavin-induced photo-oxidation of folic acid are p-aminobenzoylglutamic acid and a carbonyl compound, presumably 2-amino-4-hydroxy-6-pteridine-carboxaldehyde.
Abstract: Folic acid undergoes oxidative cleavage on exposure to light, and riboflavin markedly intensifies this action of light. As little as 50 μg. of riboflavin per 100 cc. of solution can accelerate the destruction of 10 mg. of folic acid. The reaction is much more rapid at pH 4.0 than at pH 6.5, and is retarded when the air is replaced by nitrogen. The products of the riboflavin-induced photo-oxidation of folic acid are p-aminobenzoylglutamic acid and a carbonyl compound, presumably 2-amino-4-hydroxy-6-pteridine-carboxaldehyde. Most of the riboflavin remains undecomposed. A possible mechanism is proposed for this reaction, and other data on folic acid stability are presented.
20 citations
TL;DR: Tablets can be assayed for barbiturate or sulfa content by direct titration of a powdered sample by the acidimetric method, which is faster and more accurate than the nitrite method usually employed.
Abstract: Barbiturates are weak acids and give poor end points when titrated in alcohol or water. Titration in dimethylformamide (DMF) with sodium methoxide in benzenemethanol, however, gives very sharp visual end points. Tablets can be assayed for barbiturate or sulfa content by direct titration of a powdered sample. This method is convenient and much more rapid than the official method for barbiturates. For sulfa drugs, the acidimetric method is faster and more accurate than the nitrite method usually employed.
TL;DR: Methods are described for the estimation of Dormison in biological fluids and tissues and the in vitro demonstration of the disappearance of this structural group in the presence of tissue slices in rat tissues.
Abstract: Methods are described for the estimation of Dormison in biological fluids and tissues. A major step in the metabolism of Dormison is the destruction of the ethinyl group which occurs very rapidly in the dog as revealed by the rapid decline in blood level, low level of elimination in the urine, and the in vitro demonstration, in rat tissues, of the disappearance of this structural group in the presence of tissue slices. No evidence of storage or accumulation of the drug in the tissues was found.
TL;DR: Ferbam has a much lower acute toxicity than ziram, and in thirty-day feeding tests, weanling albino rats grew normally when diets contained 0.01 per cent of either compound.
Abstract: The increasing use of the fungicides ferbam and ziram makes imperative the presentation of additional information on their toxicities. When given in single doses intraperitoneally or orally, neither compound is highly toxic. Ferbam has a much lower acute toxicity than ziram. In thirty-day feeding tests, weanling albino rats grew normally when diets contained 0.01 per cent of either compound. Mortality was marked in groups fed an 0.5 per cent diet of ferbam. Tissues taken at the end of the tests of both compounds were normal histologically. Dogs tolerated 25 mg./Kg./day for one month without injury.
TL;DR: A bismuth subsalicylate preparation and aluminum hydroxide gels were compared with respect to their adsorption of antibiotics.
Abstract: A bismuth subsalicylate preparation and aluminum hydroxide gels were compared with respect to their adsorption of antibiotics. Adsorption did not occur on bismuth subsalicylate; however, significant adsorption occurred with the aluminum hydroxide gels.
TL;DR: All of the ingested Methocel HG was eliminated in the feces within ninety‐six hours following administration, suggesting that high gel point methylcellulose is a good source of stool softening agent for young adults.
Abstract: A high gel point methylcellulose (Methocel HG) was given in single doses to normal healthy young adults. Only minor symptoms were reported, e. g., mild laxative effect, mild constipating effect, and a few instances of commonplace symptoms such as cramping, flatus, headache, and tenesmus which apparently were not related to the ingestion of Methocel HG. Essentially all of the ingested Methocel HG was eliminated in the feces within ninety‐six hours following administration.
TL;DR: ‘Ilotycin’ has been found in the blood, urine, feces, and cerebrospinal fluid of dogs which had received the drug by mouth, and the antibiotic is basic; numerous salts have been prepared, the acute toxicity of several of which are reported.
Abstract: ‘Ilotycin’ is a crystalline antibiotic produced by an actinomycete, identified as a strain of Streptomyces erythreus. It has shown significant activity against pathogenic Gram-positive organisms and against some of the more important Gram-negative organisms such as the Neisseria, Hemophilus, and Brucella groups. Acute toxicity tests by different routes of administration to each of several species of animals have shown the antibiotic to be of low toxicity, which has been confirmed by subacute studies now underway. ‘Ilotycin’ has been found in the blood, urine, feces, and cerebrospinal fluid of dogs which had received the drug by mouth. The antibiotic is basic; numerous salts have been prepared, the acute toxicity of several of which are reported. Blood and urine levels following parenteral injections to dogs are included.
TL;DR: The lactone, sikkimot toxin, is analogous to podophyllotoxin, a component of P. peltatum L. and P. emodi Wall and a tentative formula has been suggested for it.
Abstract: The lactone, sikkimotoxin, is analogous to podophyllotoxin, a component of P. peltatum L. and P. emodi Wall. Based on the action of some oxidizing and reducing agents, acetic anhydride and acetyl chloride, a tentative formula (I) has been suggested for it.
TL;DR: It was found that for all practical purposes saccharin in aqueous buffered solutions of pH 3.3, 7.0, and 8.0 is unaffected by heating at temperatures of 100, 125, and 150° for one hour.
Abstract: The influence of pH and temperature on the hydrolysis of saccharin was studied. An ultraviolet absorption method was used to determine the amount of saccharin decomposed. The limit of accuracy of the determination represents 1 per cent decomposition. It was found that for all practical purposes saccharin in aqueous buffered solutions of pH 3.3, 7.0, and 8.0 is unaffected by heating at temperatures of 100, 125, and 150° for one hour.
TL;DR: A colorimetric method of assay is described involving the streptidine moiety of the strePTomycin and dihydrostreptomycin molecule, which is simple, reproducible, and rapid.
Abstract: A colorimetric method of assay is described involving the streptidine moiety of the streptomycin and dihydrostreptomycin molecule. The method is simple, reproducible, and rapid. Comparative results between the chemical assay and the microbiological assay are presented.
TL;DR: When liberated in base form, antihistamines may be dissolved in alcohol and titrated directly with 0.05 N aqueous sulfuric acid, or dissolved in a measured volume of the acid and the excess titrated with 1.1 N perchloric acid in dioxane; the end point is preferably determined potentiometrically but may be determined colorimetrically.
Abstract: When liberated in base form, antihistamines may be dissolved in alcohol and titrated directly with 0.05 N aqueous sulfuric acid, or dissolved in a measured volume of the acid and the excess titrated with 0.05 N aqueous sodium hydroxide; the end point is determined potentiometrically. A much simpler and more precise method is that of direct titration of either the base or salt form of antihistamines, dissolved in glacial acetic acid, with 0.1 N perchloric acid in dioxane; the end point is preferably determined potentiometrically but may also be determined colorimetrically. Interference by the halide acid component of salts is avoided by addition of mercuric acetate.
TL;DR: A partition coefficient, favoring the stationary phase, was achieved by substituting an organic-aqueous system for the water and the stability of the alkaloids was assured by using acidic wash liquids.
Abstract: The problem of separation of ergot alkaloids in solvent systems is complicated by the varied solubility of the alkaloids and by their instability. The conventional procedure of paper partition chromatography, in which water is the stationary phase, does not separate the ergotoxine and ergotamine alkaloids since they follow the solvent front of the wash liquid. A partition coefficient, favoring the stationary phase, was achieved by substituting an organic-aqueous system for the water. The stability of the alkaloids was assured by using acidic wash liquids.
TL;DR: It is postulated that high lipoid solubility of digitoxin and acetyl digoxin assures absorption of solid and dissolved states, whereas low lipoidsolubility retards absorption of digoxin tablets and lanatoside C in solid or in solution.
Abstract: Digitoxin, acetyl digoxin, digoxin, and lanatoside C were administered orally to unanesthetized cats in single fatal doses. Physical state of subdivision and lipoid solubility appeared to modify rate of absorption. Digitoxin, acetyl digoxin, and digoxin were rather uniformly and nearly completely absorbed within a few hours, provided they were dissolved in aqueous alcohol or aqueous “Tween 80” solutions. Lanatoside C was slowly absorbed in alcoholic solution. Digoxin and lanatoside C tablets were absorbed very slowly. Lanatoside C is much less lipoid‐soluble than the others. It is postulated that high lipoid solubility of digitoxin and acetyl digoxin assures absorption of solid and dissolved states, whereas low lipoid solubility retards absorption of digoxin tablets and lanatoside C in solid or in solution. Acetyl digoxin deserves clinical trial as a substitute for digitoxin. Digoxin in alcohol or “Tween 80” solution should be as potent as digitoxin in solution.
TL;DR: Iodine solution N. F. IX was found to be effective against the spores of B. anthracis,B.
Abstract: Since the latter part of the 19th century, much has been written extolling the alleged virtues of iodine as an antiseptic. The sporicidal action of iodine has been reported but discrepancies appear in the results. Comparative studies have been made between water and water-alcoholic iodine solutions in which the water solutions have consistently been shown to be more efficient. This in vitro study reports on the sporicidal efficiency of a 2 per cent water-iodine solution (iodine solution N. F. IX). Both “wet” and “dry” techniques were employed, using conditions with different pH values. Iodine solution N. F. IX was found to be effective against the spores of B. anthracis, B. subtilis, B. megatherium, B. mesentericus, and Cl. tetani.
TL;DR: In this article, two simple and rapid methods for the assay of isonicotinic acid hydrazide are presented, one dealing with titration of the drug in anhydrous medium with perchloric acid, while the other has as its principle the oxidation by means of iodine in an alkaline solution.
Abstract: Two simple and rapid methods for the assay of isonicotinic acid hydrazide are presented. One of these methods deals with the titration of the drug in anhydrous medium with perchloric acid, while the other has as its principle the oxidation by means of iodine in an alkaline solution.
TL;DR: Crystalline vitamin B 12 was found to be chemically compatible with other B vitamins and some pharmaceutically useful solvents and stable at room temperature in sterile aqueous solutions or those containing small amounts of sodium chloride, freshly redistilled phenol, or benzyl alcohol.
Abstract: Some pharmaceutical properties of crystalline vitamin B 12 are reported. The anhydrous solid is hygroscopic and may absorb about 12 per cent of moisture. The solid presents no unusual stability problem in the hydrated form, and is also stable in dry triturations with mannitol, sodium chloride, and certain sugars. The vitamin is quantitatively adsorbed on talc. Crystalline vitamin B 12 is stable at room temperature in sterile aqueous solutions or those containing small amounts of sodium chloride, freshly redistilled phenol, or benzyl alcohol. An incompatibility has been observed between vitamin B 12 and trace substances occurring in some samples of liquefied phenol U. S. P. On the basis of accelerated tests and long‐term storage tests, crystalline vitamin B 12 was found to be chemically compatible with other B vitamins and some pharmaceutically useful solvents.
TL;DR: By means of cobalt 60 labeled vitamin as radioactive tracer, the stability of vitamin B12, after thirteen months' storage in four different multivitamin combinations, has been determined.
Abstract: By means of cobalt 60 labeled vitamin as radioactive tracer, the stability of vitamin B12, after thirteen months' storage in four different multivitamin combinations, has been determined. The cobalt 60 labeled vitamin B12, prepared by microbial synthesis, was extracted from the multivitamin preparations by using three separate solvents, and determined by its radioactivity.
TL;DR: Khellin (2-methyl-5,8-dimethoxyfurochromone), C14H12O5 when refluxed with hydrobromic acid, yields a partially demethylated compound named by us as desmethylkhellin, C12H10O5.
Abstract: Khellin (2-methyl-5,8-dimethoxyfurochromone), C14H12O5 when refluxed with hydrobromic acid, yields a partially demethylated compound named by us as desmethylkhellin (2-methyl-5-hydroxy-8-methoxyfurochromone), C12H10O5. It occurs as deep yellow prisms, m. p. 201′. Methylation of desmethylkhellin with either diazomethane or methyl iodide results in the formation of khellin. The acetyl derivative of desmethylkhellin was prepared in the usual manner. The ethyl, n-propyl, n-butyl, allyl, carbethoxymethyl, acetamido, phenacyl, and beta-diethylaminoethyl derivatives were prepared by refluxing the appropriate halide with desmethylkhellin in acetone with anhydrous potassium carbonate. Hydrolysis of the carbethoxymethyl derivative yielded carboxymethyldesmethylkhellin.
TL;DR: The unsatisfactory results obtained with the emodin type of drugs led to the development of a satisfactory method of bioassay on rats, and suitable standards were developed for comparable bioassays of several cathartics of the emmodin type.
Abstract: Tests of cathartics on the usual types of laboratory animals were reviewed. The unsatisfactory results obtained with the emodin type of drugs led to the development of a satisfactory method of bioassay on rats. The DD50 was determined by administration to a significant number of animals at several dosage levels; the consistency of the expressed fecal matter was determined eighteen hours later. Suitable standards were developed for comparable bioassays of several cathartics of the emodin type. The precision of these studies was about 15 per cent.
TL;DR: Local anesthetic activity, as measured on the rabbit cornea, is maximal when the isoquinoline is substituted in the 3-position by a butyl group and in the 1- position by a 3-(1-methylpiperidyloxy) group.
Abstract: The preparation, properties, and local anesthetic activity of a series of 1-aminoalkoxy-isoquinoline derivatives and the requisite 1-chloroisoquinoline intermediates are reported. In general, local anesthetic activity, as measured on the rabbit cornea, is maximal when the isoquinoline is substituted in the 3-position by a butyl group and in the 1-position by a 3-(1-methylpiperidyloxy) group.
TL;DR: Instrumental methods are described for the identification and assay of isonicotinic acid hydrazide in the crystalline form and in tablets, which offers a highly specific means for qualitative differentiation from isomers and closely related compounds.
Abstract: Instrumental methods are described for the identification and assay of isonicotinic acid hydrazide in the crystalline form and in tablets. Infrared absorption spectrophotometry offers a highly specific means for qualitative differentiation from isomers and closely related compounds. Ultraviolet absorption spectrophotometry provides a simple means of assay, which, while not specific in the presence of related compounds, does differentiate from isomers by means of the wave lengths and absorbancy ratio at the maximum and minimum. Polarography affords an alternate assay method free from interference by isomers and related compounds.