Showing papers in "Journal of the American Pharmaceutical Association in 1953"
TL;DR: Antimicrobial studies show that the methyl, ethyl, propyl, and butyl esters are effective in low concentrations against fungi and Gram-positive bacteria, but less effective against Gram-negative bacteria.
Abstract: The history of the esters of p-hydroxybenzoic acid and their uses as preservatives in pharmaceuticals, cosmetics, foods, and industrial products are discussed. Antimicrobial studies show that the methyl, ethyl, propyl, and butyl esters are effective in low concentrations against fungi and Gram-positive bacteria, but less effective against Gram-negative bacteria. The esters are more fungistatic than fungicidal. The p-hydroxybenzoates were also tested against microorganisms in the presence of humans serum, and against the growth of A. niger in procaine nicillin suspensions. The physical and chemical proprties of the p-hydroxygnwates are extensively described, as well as methods of incorporation and a method of determination by ultraviolet absorption.
122 citations
TL;DR: It is reported that phenylethyl alcohol in relatively low concentrations (1:400) exerts an effective inhibitory action on Gram‐negative bacteria and may thus be used for differential inhibition.
Abstract: The inhibitory action of phenylethyl alcohol on the growth of several bacteria has been determitied. The resulrs reported indicate that phenylethyl alcohol in relatively low concentrations (1:400) exerts an effective inhibitory action on Gram‐negative bacteria and may thus be used for differential inhibition.
84 citations
TL;DR: The data obtained for the sulfathiazole granulations studied indicate that there is a logarithmic relationship between the compressional force and the apparent density or the porosity of the tablets and that the pressure distribution inside the die cavity during the compression process appears to be quite uniform.
Abstract: A study has been made of the influence of compressional force employed in tablet compression on the apparent density, porosity, hardness, disintegration time, and average primary particle size of compressed tablets, The data obtained for the sulfathiazole granulations studied indicate that there is a logarithmic relationship between the compressional force and the apparent density or the porosity of the tablets and that the pressure distribution inside the die cavity during the compressional process appears to be quite uniform. Neither hardness nor disintegration time seems to be strongly influenced by granulation size distribution. The following appear to have linear relationships: the plot between Strong Cobb Hardness and the logarithm of the compressional force; hardness and porosity; and the logarithm of disintegration time when plotted against the compressional force. The specific surface areas of compressed tablets undergo marked changes during the compressional process, exhibiting pronounced maxima at 2,500 lbs. for 3/8‐inch tablets.
81 citations
48 citations
39 citations
TL;DR: New data are presented, and the results of earlier studies are reviewed and explained in terms of the fundamental driving forces behind the availability of antimicrobial agents in such systems.
Abstract: Surface-active agents modify biological results, but their effect can be related to wellknown thermodynamic quantities. New data are presented, and the results of earlier studies are reviewed and explained in terms of the fundamental driving forces behind the availability of antimicrobial agents in such systems.
39 citations
TL;DR: Experimental evidence is offered to support the existence of at least one type of complex between caffeine and benzoate ion and the approximate stability constants for these systems have been determined at several temperatures to permit tentative estimation of the heats and entropies of the reactions.
Abstract: The stoichiometry and the nature of interactions between caffeine and benzoic acid are discussed. Experimental evidence is offered to support the existence of at least one type of complex between caffeine and benzoate ion. The approximate stability constants for these systems have been determined at several temperatures to permit tentative estimation of the heats and entropies of the reactions.
38 citations
TL;DR: The equilibrium reactions leading to complex formation between caffeine and six pharmaceuticals have been studied and it is shown that complex formation may lead to either a decrease or an increase in the solubilities of the reactants.
Abstract: The equilibrium reactions leading to complex formation between caffeine and six pharmaceuticals have been studied. The stability constants at several temperatures, the heats of reaction, and the entropy changes have been approximated. It is shown that complex formation may lead to either a decrease or an increase in the solubilities of the reactants. The influence of structure on equilibrium is also discussed.
30 citations
TL;DR: Monkey, guinea pig, and rabbit susceptibility approached that shown by rats while dogs were somewhat more resistant, though succumbing to higher levels.
Abstract: The toxicity to laboratory animals of 3-(acetonylbenzyl)-4-hydroxycoumarin (warfarin), used as the sodium salt, is described. It is shown that the acute oral LD50's of the salt range from 58 mg./Kg. for the female rat (male: 323) to greater than 1 Gm./Kg. for the chicken. Prior castration increases male and decreases female rat susceptibility to acute warfarin dosage. Subacute dietary feeding caused deaths in rats at 6.25 p. p. m. in about 10 days while chickens survived 100 p. p. m. for the fifty days fed, though succumbing to higher levels. Monkey, guinea pig, and rabbit susceptibility approached that shown by rats while dogs were somewhat more resistant.
30 citations
TL;DR: A series of thirty N2-substitution products of N1-isonicotinyl hydrazine has been prepared and characterized and the majority of the substances had an in vivo antitubercular activity of the same order of magnitude as that of isonicotinic hydrazide.
Abstract: A series of thirty N2-substitution products of N1-isonicotinyl hydrazine has been prepared and characterized. The majority of the substances had an in vivo antitubercular activity of the same order of magnitude as that of isonicotinic hydrazide. A short series of other compounds which can also be considered as derivatives of isonicotinic hydrazide has also been prepared and characterized but found to be devoid of any significant antitubercular action.
30 citations
TL;DR: Evidence suggests that the active fraction of the Rbodomela extracts may be a brominated phenolic compound, and attempts are being made to purify the compound.
Abstract: Ether extracts of the marine red alga, Rbodomela larix, inhibit the growth of several species of Gram‐positive and Gram‐negative pathogens in vitro. Present evidence suggests that the active fraction of the Rbodomela extracts may be a brominated phenolic compound. Attempts are being made to purify the compound.
TL;DR: Iodine solubilized in a surface-active agent solution is shown to be an effective antibacterial agent and to be devoid of most of the disadvantages found in the common iodine solutions.
Abstract: Iodine solubilized in a surface-active agent solution is shown to be an effective antibacterial agent. An equation is given by which it is possible to calculate the equilibrium concentration of iodine freely dispersed in water (in contrast to micellular iodine). Correlation between this calculated concentration of iodine in water and the 99 per cent killing time is presented. Preliminary data further show the solution to be devoid of most of the disadvantages found in the common iodine solutions.
TL;DR: Two crystalline compounds, named ambrosin and damsin, were isolated and were shown to contain a carbonyl group and a lactone group, but upon pharmaceutical examination were found to exhibit low activity for the tests made.
Abstract: Ambrosia maritima L., used as a popular drug in Egypt, was studied to determine whether it contained active therapeutic principles. Two crystalline compounds, named ambrosin and damsin, were isolated. They were shown to contain a carbonyl group and a lactone group, but upon pharmaceutical examination were found to exhibit low activity for the tests made.
TL;DR: A critical evaluation is made of previous theories concerning the relationship between laxative potency and chemical structure and of the methods of assaying, and it will be seen that compounds which have laxative roperties possess at least two phenolic hydroxyls and at least three rings in their molecules.
Abstract: A review is presented of laxatives of organic structure, mostly phthaleins, phthalein derivatives, and hydroxyanthraquinones. A critical evaluation is made of previous theories concerning the relationship between laxative potency and chemical structure and of the methods of assaying. Thirty-six organic compounds were prepared and tested for laxative action, usin the resus monkey as a test animal. A precise rule for correlating potency and molecular structure cannot be stated at this time. However, it will be seen that compounds which have laxative roperties possess at least two phenolic hydroxyls and at least three rings in their molecules.
TL;DR: Although the majority of the substances prepared exhibited no useful in vivo antitubercular activity, some of them had an activity of the same order of magnitude as that of isonicotinic hydrazide.
Abstract: A series of twenty-four nonpyridinoid heterocyclic hydrazides representing ten different heterocyclic nuclei has been prepared and characterized. Although the majority of the substances prepared exhibited no useful in vivo antitubercular activity, some of them had an activity of the same order of magnitude as that of isonicotinic hydrazide.
TL;DR: Experimental data obtained from sulfathiazole, barbiturates, and terramycin indicate that deviations from the expected relationships are usually small unless complex formation takes place.
Abstract: A study has been made to determine the validities of certain theoretical relationships, based on the law of mass action, which predict the influence of pH, electrolyte concentration, and additives such as alcohol on solubilities of weakly acidic pharmaceuticals. Experimental data obtained from sulfathiazole, barbiturates, and terramycin indicate that deviations from the expected relationships are usually small unless complex formation takes place.
TL;DR: A study was made of the possible adsorption of various drugs often given simultaneously with aluminum compounds in the treatment of gastric hyperacidity, and a number of drugs tested were adsorbed by aluminum hydroxide gel, while certain other aluminum antacids did not cause adsor adaptation to the same extent, if at all.
Abstract: A study was made of the possible adsorption of various drugs often given simultaneously with aluminum compounds in the treatment of gastric hyperacidity. The approximate LD90 for each drug upon oral administration to mice was found, and the same dose was then given in admixture with various aluminum preparations to determine if the same LD was obtained. A number of drugs tested were adsorbed by aluminum hydroxide gel, while certain other aluminum antacids did not cause adsorption to the same extent, if at all.
TL;DR: Tween-80 is found to be more effective than serum, serum albumin, and globulin in inactivating the antibacterial properties of as much as 0.1 per cent Hexachlorophene in broth.
Abstract: The use of nonionic surface-active agents for the inactivation of Hexachlorophene (G-11) is discussed. Tween-80 is found to be more effective than serum, serum albumin, and globulin in inactivating the antibacterial properties of as much as 0.1 per cent Hexachlorophene in broth. In hand and arm wash studies using Hexachlorophene soaps, Tween-80 is found to give a much higher number of surviving organisms than in those in which serum was used.
TL;DR: The stems of Banisteriopsis inebrians were found to contain 0.15 per cent of the alkaloid harmine, but the other alkaloids that accomany harmine in peganum harmala could not be detected.
Abstract: The stems of Banisteriopsis inebrians were found to contain 0.15 per cent of the alkaloid harmine, but the other alkaloids that accomany harmine in peganum harmala could not be detected. The leaves were found to contain an alkaloid which was partly identified as harmine.
TL;DR: In this article, the calcium chelate of ethylenediamine tetracetic acid has been shown to accelerate the urinary excretion of yttrium and plutonium, and the results were produced whether the chelating agent was given shortly after or early after radio element was administered.
Abstract: It has been demonstrated that certain chelating agents can be used to hasten the excretion of radioelements which have become deposited in the body. Specifically, the calcium chelate of ethylenediamine tetracetic acid has been shown to accelerate the urinary excretion of yttrium and plutonium. Similarly, Fe‐3, a commercial chelating agent was found to accelerate the urinam excretion of plutonium. The results were produced whether the chelating agent was given shortly after or early after the radioelement was administered. The increased excretion of the plutonium was reflected in a lower Pu content in the tissues of the treated animals.
TL;DR: Results indicate that niacinamide is the best of the solubilizers studied, and solutions show no significant loss of potency of either the folic acid or the vitamin B12 after storage at room temperature and under accelerated conditions, and display satisfactory stability with respect to clarity of solution.
Abstract: The low solubility of folic acid in water, except at a relatively high pH, has prevented its use in parenteral solutions in combination with vitamin B12 (cyanocobalamin), which attains optimum stability in the pH range 4 to 6.5. The present study utilizes selected solubilizers for folic acid, including aminoacetic acid, methyl glucamine, and niacinamide within a pH range of 6 to 6.5. Results indicate that niacinamide is the best of the solubilizers studied. By special processing it is possible to dissolve and maintain in solution 5 mg. of folic acid per cc. at pH 6 under conditions compatible with crystalline vitamin B12 at a concentration of 30 μg. per cc. Solutions show no significant loss of potency of either the folic acid or the vitamin B12 after storage at room temperature and under accelerated conditions, and display satisfactory stability with respect to clarity of solution.
TL;DR: The isotope dilution procedure of analysis, a relatively new technique, offers intriguing possibilities and is of sufficient importance to warrant special attention at this time.
Abstract: The isotope dilution procedure of analysis, a relatively new technique, offers intriguing possibilities and is of sufficient importance to warrant special attention at this time. The history of the procedure and a survey of the literature are presented.
TL;DR: Morphine can be separated from codeine by a strongly basic, quaternary amine-type anion exchanger, where morphine base, due to its phenolic structure, exchanges with the resin while the codeine base does not.
Abstract: Morphine can be separated from codeine by a strongly basic, quaternary amine-type anion exchanger. The morphine base, due to its phenolic structure, exchanges with the resin while the codeine base does not. Codeine is washed through the column with the solvent and is determined by titration. Morphine is then qualitatively removed from the column with dilute acid and determined spectrophotometrically.
TL;DR: An assay of morphine in opium is proposed which utilizes both adsorption and colorimetric procedures.
Abstract: An assay of morphine in opium is proposed which utilizes both adsorption and colorimetric procedures.
TL;DR: The present study is an example of how kinetic studies can be used to elucidate the mechanism of breakdown of complex drugs.
Abstract: A chemical kinetics study of the rate of formation of chloride ions in aqueous solutions of chloramphenicol at elevated temperatures has been made. The data obtained indicate that the over-all rate of chloride production is a summation of the rates of at least three first-order reactions: direct uncatalyzed hydrolytic cleavage of chlorine ions from whole chloramphenicol molecules, direct hydroxyl ion catalyzed cleavage of chloride ions from whole chloramphenicol molecules, and hydrolysis of chloramphenicol at the amide linkage, then subsequent hydrolysis of the dichloroacetate ions formed to yield chloride ions and other degradation products. The rates of the several reactions have been separated by mathematical analysis from each other in the over-all rate and the heats of activation have been determined. The results for the dichloroacetate reaction are in excellent agreement with those of Kunze. The present study is an example of how kinetic studies can be used to elucidate the mechanism of breakdown of complex drugs.
TL;DR: Results of acute toxicity tests in rodents indicated that the two alkyl aryl sulfonates studied may be classified as only moderately toxic, and continued feeding of the compounds resulted in no evidence of cumulative toxicity.
Abstract: Results of acute toxicity tests in rodents indicated that the two alkyl aryl sulfonates studied may be classified as only moderately toxic. Acutely poisoned animals showed evidence of stimulation and irritation of the digestive tract. The mechanism of death is obscure, since the tissue lesions were neither extensive nor pathognomonic; both compounds, however, showed more hemolytic activity in vitro than sodium stearate. No noticeable systemic effect followed cutaneous application, nor were there local reactions of significance. Continued feeding of the compounds to rodents resulted in no evidence of cumulative toxicity. The ingestion of small quantities would seem to be harmless.
TL;DR: It has been found that the responsible agent lies in the volatile oil, which is present to the extent of about 0.005% of the fresh overground portion of celery, and Mannitol was found in abundance.
Abstract: In an investigation into the cause of dermatitis from celery, it has been found that the responsible agent lies in the volatile oil, which is present to the extent of about 0.005% of the fresh overground portion. Long range experiments are now under way to determine if workers in the field can be desensitized by injections of the diluted oil. During the course of the examination, the marketable portions have been submitted to proximate analysis and fractionation. Mannitol was found in abundance and some of the properties of the oil have been determined.
TL;DR: Some of the opium alkaloids and meconic acid were separated and identified by the use of surface chromatography using a fluorescent adsorbent buffered at pH 6.6 and chromatograms were developed using 1,4-dioxane.
Abstract: Some of the opium alkaloids and meconic acid were separated and identified by the use of surface chromatography. The strips were coated with a fluorescent adsorbent buffered at pH 6.6. The chromatograms were developed using 1,4-dioxane. Identification of the individual opium alkaloids on the strips was accomplished by means of Rf values determined with pure samples, coupled with the observation of the extinction of fluorescence at the area of adsorption of the alkaloids. As little as 15–20 micrograms of papaverine hydrochloride, narcotine, or meconic acid, and 50 micrograms of morphine, codeine, or narceine could be detected by this method.
TL;DR: The effect of granulation particle size on the weight variation of compressed tablets was studied, using statistical quality control procedures, and sodium chloride was found to give a minimum at 200 to 500 microns.
Abstract: The effect of granulation particle size on the weight variation of compressed tablets was studied, using statistical quality control procedures. Batches of lactose-starch granulation particles ranging in size from 3,045 to 324 microns and separated into narrow-size ranges were compressed in a single-punch tablet press. As the particle size decreased, the tablet weight variation decreased, passed through a minimum at 400 to 800 microns and then increased. Data from a somewhat similar experiment involving sodium chloride was found to give a minimum at 200 to 500 microns.
TL;DR: A modified procedure, involvin decolorization of the ammonium salt, is feescribed for the purification of crude ursolic acid obtained from cranberries.
Abstract: A modified procedure, involvin decolorization of the ammonium salt, is feescribed for the purification of crude ursolic acid obtained from cranberries. Oleanolic acid was isolated from the mother liquors remaining from the final recrystallization of the purified product.