Showing papers in "Journal of the American Pharmaceutical Association in 1959"
TL;DR: A new method of rapidly coating drug particles of widely varying size and shape is presented, in this process, the drug particles are coated and dried while suspended in an upwardly moving current of air.
Abstract: A new method of rapidly coating drug particles of widely varying size and shape is presented. In this process, the drug particles are coated and dried while suspended in an upwardly moving current of air. Solutions and suspensions of coating materials in both water and volatile organic solvents are employed. The drying of the coated particles is accomplished at either room or elevated temperatures, depending on the solvent used. Some fundamentals and an introduction to practical applications of the process are given.
120 citations
TL;DR: 7-Chloro-4-indanol is well tolerated by skin, eyes, genital mucosa; it is nonallergenic; it appears to be suitable for use as topical antiseptic or sanitizer.
Abstract: 7-Chloro-4-indanol in concentrations of 1:1,000–1:3,000 is rapidly lethal to vegetative bacteria, Trichophyton sp., C. albicans, E. histolytica cysts and trophozoites, T. vaginalis , and spermatozoa in vitro . Systemic toxicity is low; it is well tolerated by skin, eyes, genital mucosa; it is nonallergenic; it appears to be suitable for use as. topical antiseptic or sanitizer.
68 citations
TL;DR: Determination of meprobamate concentrations in blood specimens from normal adult subjects indicates that a peak concentration of this drug is attained about two hours after oral administration.
Abstract: A colorimetric procedure is described for the microdetermination of meprobamate in biological fluids Meprobamate is extracted from plasma or serum using mixed chloroform-carbon tetrachloride solvent, and color development is effected by treatment with p -dimethylaminobenzaldehyde and antimony trichloride in acetic anhydride The color intensity measured at 550 mμ is proortional to the concentration over the range of 05 to 10 mcg A suitable modigation of the extraction procedure for use with urine specimens is also described, which permits separation of meprobamate from the higher concentration of endogenous interfering substances present in urine Determination of meprobamate concentrations in blood specimens from normal adult subjects indicates that a peak concentration of this drug is attained about two hours after oral administration
60 citations
TL;DR: A new source of radio-opaque compounds for the development of hepatolienography contrast media consists of the class of tetraiodophthalic anhydride derivatives.
Abstract: A new source of radio-opaque compounds for the development of hepatolienography contrast media consists of the class of tetraiodophthalic anhydride derivatives. Hydroxyethyl and hydroxypropyl tetraiodobenzoates were prepared by the decarboxylation of hydroxyethyl and hydroxypropyl tetraiodophthalates. These compounds gave good colloidal dispersions by precipitation in water from acetone. Zirconyl tetraiodophthalate was prepared as a colloidal precipitate, but hydrolysis took place in attempts to neutralize the solvent.
52 citations
TL;DR: This paper showed that small injections given between trruning trials increased the drug-directed behavior, probably because they retarded, but did not revent, some loss of tolerance and dependence during the procedure.
Abstract: As in revious experiments with this procedure, relapse by animals was demonstratecf Different degrees of drug-directed behavior were produced in groups of rats which underwent escape training. Small injections given between trruning trials increased the drug-directed behavior, probably because they retarded, but did not revent, some loss of tolerance and dependence during the procedure. It seems likeg that the time interval between training trials is too long and should be shortened for maximal effect on drug-seeking behavior. More important, this experiment indicates that for rats, as for man, the conditions under which morphine is received is more highly related to the development of drug-seeking behavior than is any “inherent rewarding properties” of morphine.
38 citations
38 citations
TL;DR: In this paper, the preparation, surface, and infiltration activities and toxicity of diethylaminoacetanilide and seven of its derivatives are described, and the toxicity of seven derivatives is analyzed.
Abstract: The preparation, surface, and infiltration activities and the toxicity of diethylaminoacetanilide and seven of its derivatives are described.
31 citations
TL;DR: An investigation of the role played by various properties and characteristics of crystals and the ability of these crystals to form tablets when subjected to direct compression found crystal system, binary compounds, water of crystallization, boiling point, carbonate radical, sulfate radical and substances forming structurally neutral layer lattices, were found to influence tablet formation.
Abstract: An investigation of the role played by various properties and characteristics of crystals and the ability of these crystals to form tablets when subjected to direct compression was made. Crystal system, binary compounds, water of crystallization, boiling point, carbonate radical, sulfate radical, and substances forming structurally neutral layer lattices, were found to influence tablet formation.
30 citations
TL;DR: The use of urinary excretion data to evaluate drug absorption was discussed from the theoretical viewpoint and results of studies conducted to determine absorption of aspirin, benzyl penicillin, and sulfaethylthiadiazole were interpreted.
Abstract: The use of urinary excretion data to evaluate drug absorption was discussed from the theoretical viewpoint and results of studies conducted to determine absorption of aspirin, benzyl penicillin, and sulfaethylthiadiazole were interpreted according to these considerations. It was shown that the absorption of aspirin was apparently rate limited by the time necessary for this drug to dissolve in vivo and that benzyl penicillin absorption appeared to be rate limited by the intrinsic solution rate properties of the salts used. The absortion rate of sulfaethylthiadiazole was calculated by means of excretion rate data and the results obtained shown to be in excellent agreement with calculation of the same quantity made from previously reported blood level data. The calculated absorption rate of this drug was about 1,200 mg./hr., fifteen to thirty minutes after the ingestion of 1-Gm. doses.
30 citations
TL;DR: Measurements carried out on purines, DNA, B vitamins, etc., show that such biochemicals are, in general, relatively strong complexing agents.
Abstract: The present study extends the investigation of complexing tendencies of oxytetracycline to ( a ) a series of isomer, multifunctional aromatic compounds, ( b ) certain biochemicals, ( c ) calcium and magnesium ions, both free and as chelates, and ( d ) hexametaphosphate. The relative importance of grouping and their location on the binding tendency has been demonstrated. Measurements carried out on purines, DNA, B vitamins, etc., show that such biochemicals are, in general, relatively strong complexing agents. Data on alkali earths suggest that complexed drugs may still undergo chelation. Hexametaphosphate appears to undergo very slight, if any, complexing reaction with either tetracycline or oxytetracycline at pH values between 5 and 8.
28 citations
TL;DR: Data are presented to show that the preservative activity of p -hydroxybenzoic acid esters in the presence of Tween 80 is primarily a function of the concentration of unbound preservative.
Abstract: Data are presented to show that the preservative activity of p -hydroxybenzoic acid esters in the presence of Tween 80 is primarily a function of the concentration of unbound preservative. Prediction of required preservative concentrations from a knowledge of the degree of interaction of the preservative with nonionic surfactants is illustrated.
TL;DR: Gamma-thujaplicin (2-hydroxy-5-isopropyl-2,4,6-cycloheptatrien-1-one), a tropolone derivative occurring in western red cedar, has been found to exert a combination of stimulant and deressant actions on the mammalian central nervous system and only depression in frogs.
Abstract: Gamma-thujaplicin (2-hydroxy-5-isopropyl-2,4,6-cycloheptatrien-1-one), a tropolone derivative occurring in western red cedar, has been studied pharmacologically in the form of its sodium salt (T-Na). It has been found to exert a combination of stimulant and deressant actions on the mammalian central nervous system and only depression in frogs. Stimulant effects, in the form of convulsions shown to be of cerebral origin, are evident only in untreated animals. Certain signs of depression can also be observed in untreated animals while further depressant actions are revealed only in animals which have been treated with narcotic drugs. T-Na reduces the responses of isolated frog skeletal muscle and antagonizes the action of some stimulant drugs on isolated intestinal muscle.
TL;DR: Several cellulose and glyceryl esters were studied and their permeability shown to vary with the relative polarity of these compounds, and the influences of such variables as temperature, relative humidity, and compositions of mixtures were investigated.
Abstract: Apparent diffusivity and permeability of a variety of materials commonly employed to delay drug release from certain dosage forms have been evaluated using the lag time method. Several cellulose and glyceryl esters were studied and their permeability shown to vary with the relative polarity of these compounds. The influences of such variables as temperature, relative humidity, and compositions of mixtures were investigated. Thermal coefficients obtained for glyceryl monostearate sugest that the apparent overall heat of activation for permeation is about 8 Kcal./mole. The same system exhibits a very high dependency on relative humidity showing proportionally higher permeability near saturation than at lower values.
TL;DR: The “escape reaction” method of measuring the end point of sleeping time in mice was compared to the “righting-reflex’ method, which was found to be more reliable, to have a more definite end point, and to measure more effectively lower levels of CNS depression.
Abstract: The “escape reaction” method of measuring the end point of sleeping time in mice was compared to the “righting-reflex” method. The former was found to be more reliable, to have a more definite end point, to measure more effectively lower levels of CNS depression, and to measure cortical rather than midbrain reflexes.
TL;DR: In this paper, a direct correlation was found between excretion rate at one, two, and three hours and in vitro solution rate of the drugs when the dose was given in the form of two 0.95 cm. diameter pellets.
Abstract: Tetracycline absorption was studied by means of excretion rate measurements in humans after 200-mg. doses of tetracycline or its salts. A direct correlation was found between excretion rate at one, two, and three hours and in vitro solution rate of the drugs when the dose was given in the form of two 0.95-cm. diameter pellets. Differences in rate were less noticeable when the dose given consisted of particles having an average diameter of 100 microns. The absorption of tetracycline, tetracycline phenolsulfonphthaleinate, and tetracycline sodium hexametaphosphate complex was rate-limited by in vivo solution rate to some degree. Tetracycline hydrochloride absorption was rate-limited by the absorption process itself. The bases for these correlations were discussed. The mathematics of urinary excretion was considered to the extent of pointing out the relationship between excretion rate and blood level.
TL;DR: The structure of germanitrine, a highly active hypotensive ester alkaloid, has been elucidated and germine 3-angelate 7-acetate 15- l -2′-methylbutyrate, synthesized from germine, was found to be identical with german itrine.
Abstract: The structure of germanitrine, a highly active hypotensive ester alkaloid, has been elucidated. Germine 3-angelate 7-acetate 15- l -2′-methylbutyrate, synthesized from germine, was found to be identical with germanitrine.
TL;DR: Paper chromatographic systems and column partition systems suitable for analyzing triamcinolone in pharmaceutical preparations and in extracts of biological samples are described.
Abstract: Paper chromatographic systems and column partition systems suitable for analyzing triamcinolone in pharmaceutical preparations and in extracts of biological samples are described. Comparative mobilities of related steroids are reported for the several systems. Both qualitative and quantitative aspects of the chromatographic operations are described.
TL;DR: The lauryl sulfate salts of palladium phenothiazine derivative complexes provide a colorimetric means of following oxidative decomposition in such pharmaceutically important compounds as promazine, promethazine, and chlorpromazine.
Abstract: The lauryl sulfate salts of palladium phenothiazine derivative complexes provide a colorimetric means of following oxidative decomposition in such pharmaceutically important compounds as promazine, promethazine, and chlorpromazine. This rapid and highly specific method is well suited to routine assay of the intact drugs. The need for initial separation is eliminated in many cases.
TL;DR: In this article, the effects of dihydroxy aluminum sodium carbonate (DASC), aluminum hydroxide, calcium carbonate, and sodium bicarbonate, upon the proteolytic activity and volume of gastric secretion of the histamine-stimulated, pyloric-ligated rabbit have been studied.
Abstract: The effects of dihydroxy aluminum sodium carbonate (DASC), aluminum hydroxide, calcium carbonate, and sodium bicarbonate, upon the proteolytic activity and volume of gastric secretion of the histamine-stimulated, pyloric-ligated rabbit have been studied. The probable clinical importance of the several factors that were observed has prompted the formulation of an “Index of Effectiveness” to be used as a means of evaluating gastric antacids. This index employs four factors: the maintenance of pH within the range of 3 to 5.5, in vitro acid consuming power, proteolytic activity, and the volume of the gastric secretion. Using this index, the antacids in order of decreasing effectiveness were: dihydroxy aluminum sodium carbonate, calcium carbonate, sodium bicarbonate, and aluminum hydroxide.
TL;DR: The magnitude of any intermolecular association occurring in aqueous solution between methyl- and propylparaben and several hydrophilic polymers was determined and parabens were found to interact to some extent with polyethylene glycol 4000, methylcellulose, polyvinylpyrrolidone, and gelatin.
Abstract: The magnitude of any intermolecular association occurring in aqueous solution between methyl- and propylparaben and several hydrophilic polymers was determined. Parabens were found to interact to some extent with polyethylene glycol 4000, methylcellulose, polyvinylpyrrolidone, and gelatin. There was no evidence for a significant degree of interaction between the parabens and carboxymethylcellulose or tragacanth. The significance of these results relative to preservation of solutions containing these polymers is considered.
TL;DR: An aueous sustained release suspension of sulfaethidole (sulfaethylthiadiazole or SETD) was prepared and velocity constant for drug disappearance from blood in adult human subjects was utilized to approximate the quantity of drug to be administered every twelve hours in order to maintain free SETD blood concentrations near 10mg.
Abstract: An aueous sustained release suspension of sulfaethidole (sulfaethylthiadiazole or SETD) was prepared. The velocity constant ( K b ) for drug disappearance from blood in adult human subjects was utilized to approximate the quantity of drug to be administered every twelve hours in order to maintain free SETD blood concentrations near 10mg. per cent. Dissolution characteristics of this sustained release suspension were also studied in vitro in three different test fluids. Possible relationships with the foregoing in vivo results are discussed.
TL;DR: Few steroidal sapogenins were found, largely because of the absence of Agave, Yucca, and Dioscorea; but alkaloids were qualitatively identified in 86 species, 45 of which are new to the record.
Abstract: This report covers the fifth 1,000 accessions in a survey of plants for steroidal sapogenins and is thus a continuation of the previous four reports (1–7). Data are given for 990 accessions (all but 107 from the United States), representing 147 families, 547 genera, and 921 species. Few steroidal sapogenins were found, largely because of the absence of Agave, Yucca , and Dioscorea; but alkaloids were qualitatively identified in 86 species, 45 of which are new to the record.
TL;DR: Oral administration has been shown to produce demonstrable increases in erythropoietin in the blood and, as a result, peripheral blood values respond to an extent proportional to the dosage administered.
Abstract: The studies reported show that at dosage levels approximating those used in therapeutics, cobalt is absorbed in the rat in significant quantity. Oral administration has been shown to produce demonstrable increases in erythropoietin in the blood and, as a result, peripheral blood values respond to an extent proportional to the dosage administered.
TL;DR: One hundred and ninety-five extracts were prepared from 39 seeds of drug origin and screened in vitro against the following test organisms: Escherichia coli, Staphlococcus aureus, Serratia marcescens, Mycobacterium smegmatis, Candida albicans, Erwinia caratovora, and Streptomyces Venezuelae.
Abstract: One hundred and ninety-five extracts were prepared from 39 seeds of drug origin and screened in vitro against the following test organisms: Escherichia coli, Staphlococcus aureus, Serratia marcescens, Mycobacterium smegmatis, Candida albicans, Erwinia caratovora , and Streptomyces Venezuelae . The di-ethyl ether and acetone soluble fractions were found to possess greater antimicrobial activity than the ethyl alcohol, n -butyl alcohol, and water-soluble fractions. Sixteen of the 39 seeds were found to have no antimicrobial activity. Extracts of cardamom (green), tonka angostura, and celery were found to have antimicrobial activity on at least 6 of the 7 test organisms as well as against 12 additional microorganisms. Concentration of the extracts to less than one-half the original volume did not increase antimicrobial activity.
TL;DR: Results of the present investigation show that sympathomimetic and other drugs which are para- or ortho-hydroxybenzyl alcohol derivatives react with bisulfite to yield corresponding sulfonic acid derivatives.
Abstract: Although bisulfite is presently widely employed as an antioxidant in preparations containing drugs which readily autoxidize; the antioxidant itself, according to the study described, undergoes reaction with a number of these compounds. Results of the present investigation show that sympathomimetic and other drugs which are para- or ortho-hydroxybenzyl alcohol derivatives react with bisulfite to yield corresponding sulfonic acid derivatives. Both amino and nitrobenzyl alcohols similarly conjugated (e. g., chloramphenicol) also appear to be subject to similar reactions. The resulting sugonic acids seem to possess little or no activity.
TL;DR: Aqueous extracts of the heartwood of the Mexican plant, Haematoxylon braziletto, contain a substance which, in appropriate concentrations, is bactericidal for Salmonella typhosa and Micrococcus pyogenes var.
Abstract: Aqueous extracts of the heartwood of the Mexican plant, Haematoxylon braziletto , contain a substance which, in appropriate concentrations, is bactericidal for Salmonella typhosa and Micrococcus pyogenes var. aureus and is bacteriostatic for Escberichia coli . The active principle has not been unequivocally identified but it is suggested that the antibacterial action is due to the pigment, brazilein, or to its precursor, brazilin, or to some derivative (s) of these. Neither the unpigmented sapwood nor the bark of the plant contains the active principle. Hematoxylin, which is derived from the heartwood of the related plant, H. campechianum , and which contains pigments that are closely related chemically to those of H. braziletto , has similar antibacterial activity in similar concentrations.
Abstract: A 1.5-Kg. quantity of oven-dried Amanita pantherina was defatted and extracted exhaustively with 70% ethanol. Purification of this extract yielded a solution which contained the total chloroform-soluble alkaloids of the mushroom. Chromatographic examination of this solution revealed the resence of two comounds giving typical alkaloid reactions and a third compound which appeared to be an indole derivative. Comparison of Rf values and color reactions of these compounds with known alkaloids revealed that neither bufotenine nor hyoscyamine, nor any alkaloid giving a positive Vitali-Morin reaction, was present in the extract.
TL;DR: There was an initial increase in crude fiber content in the treated plants; however, at maturity both the treated and untreated plants showed almost the same content.
Abstract: Digitalis plants were treated two times weekly by spraying with gibberellic acid solution, representing 100 p. p. m., for about sixty days. Harvesting was done at approximately weekly intervals. A morphological and histological study of the treated plants was made. In addition, the following quantitative determinations were made: total glycosides, total sugar, digitoxose sugar, crude fiber, and chlorophyll. A marked decrease in surface area and dry weight was observed in the plants treated with gibberellic acid. Some of the treated plants developed a definite elongated stem but did not flower. An increase in total glycosides and total sugars was observed in the treated plants, but there was no significant difference in digitoxose content. An increase in chlorophyll was observed in the treated plants. There was an initial increase in crude fiber content in the treated plants; however, at maturity both the treated and untreated plants showed almost the same content.
TL;DR: The structure of germbudine has been elucidated as germine 3- d-threo -2′,3′-dihydroxy-2′-methyl butyrate 15- l -2 methylbutyrate (V).
Abstract: The structure of germbudine has been elucidated as germine 3- d-threo -2′,3′-dihydroxy-2′-methylbutyrate 15- l -2 methylbutyrate (V). Oxidation of germbudine with periodic acid and subsequent alkaline hydrolysis afforded germine 15- l -2′-methylbutyrate (VIII).
TL;DR: The tetraphenylborates of some official local anesthetics may be prepared by interacting the hydrochlorides of the organic bases with sodium tetraphhenylbron in aqueous citrate buffers at a pH of 6.0 as discussed by the authors, which affords a high degree of sensitivity, permitting the detection and quantitative estimation of these drugs.
Abstract: The tetraphenylborates of some official local anesthetics may be prepared by interacting the hydrochlorides of the organic bases with sodium tetraphenylboron in aqueous citrate buffers at a pH of 6.0. The reaction affords a high degree of sensitivity, permitting the detection and quantitative estimation of these drugs. The ultraviolet spectra of the derivatives depend, mainly, on the spectral characteristics of the organic bases. Infrared measurements are presented to confirm the mechanism of reaction and to illustrate the value of the IR data for identification purposes.