Showing papers in "Journal of the American Pharmaceutical Association in 2006"
TL;DR: A detailed phytochemical investigation of the pantropical plant Vinca rosea Linn is undertaken, finding two alkaloids, leurosine and vincaleukoblastine, possess activity against P-1534 leukemia in mice.
Abstract: As part of continuing study of alkaloid-bearing members of the family Apocynaceae , we have undertaken a detailed phytochemical investigation of the pantropical plant Vinca rosea Linn. (1). Twelve crystalline compounds have been obtained and characterized. Details of the procedure leading to the preparation of pure substances are described. Two of these alkaloids, leurosine and vincaleukoblastine, possess activity against P-1534 leukemia in mice.
152 citations
TL;DR: The in vitro antifungal activity of 92 volatile oils, 12 terpeneless oils, and 3 fixed oils was ascertained using the filter paper disk method and cinnamon, caraway, dill, and anise were found to possess the greatest antif fungus activity.
Abstract: The in vitro antifungal activity of 92 volatile oils, 12 terpeneless oils, and 3 fixed oils was ascertained using the filter paper disk method. The oils were tested against 18 pathogenic and nonpathogenic fungi. Ninety volatile oils were found to possess antifungal activity on at least one organism. Origanum (red), lemongrass (imported), thyme (red), sweet birch, savory select, coriander, sassafras, cinnamon, laurel leaves (distilled), and chenopodium exhibited the greatest antifungal activity. Streptomyces venezuelae was most susceptible to the volatile oils while Candida krusei was the most resistant. Among the terpeneless oils, cinnamon, caraway, dill, and anise were found to possess the greatest antifungal activity. The fixed oils used were found to possess no antifungal properties. Oils of chenopodium, origanum (red), and dill (terpeneless) were found to be very effective against Ustilago avenae ; chenopodium and thyme (red) against Trichophyton mentagrophytes ; and oil of cinnamon against Epidermophyton interdigitale . More than 90% of the volatile and terpeneless oils tested were found to produce fungicidal effects.
74 citations
TL;DR: A quantitative evaluation of the degree of intermolecular association between p -hydroxybenzoic acid esters and Tween® 1 80 was obtained by means of an equilibrium dialysis study employing a semipermeable nylon membrane.
Abstract: A quantitative evaluation of the degree of intermolecular association between p -hydroxybenzoic acid esters and Tween® 1 80 was obtained by means of an equilibrium dialysis study employing a semipermeable nylon membrane. Data obtained facilitate calculation of the quantity of preservative which must be added to an aqueous system containing a known concentration of Tween® 80 in order to have the desired concentration of unbound preservative.
68 citations
TL;DR: The dissolution rates of several weak acids and their sodium salts were studied in mediums representing gastrointestinal fluids with respect to pH and the significance of the results in acid-salt rate studies to oral administration of drugs was discussed.
Abstract: The dissolution rates of several weak acids and their sodium salts were studied in mediums representing gastrointestinal fluids with respect to pH. Marked differences existed between dissolution rates of acids and their sodium salts; the sodium salts always dissolved much more rapidly than the free acid. The experimental method was based on solution by free convection and an expression was derived to express dissolution rate from a circular plate suspended vertically in dissolution medium as a function of the variables involved. The validity of the expression was shown for sodium chloride dissolving in water. The significance of the results in acid-salt rate studies to oral administration of drugs was discussed.
51 citations
TL;DR: Several fields of tablet research which can benefit by the use of the Stokes Model A-3 single punch machine are discussed.
Abstract: The design and performance of an instrumented tableting machine are resented. A Stokes Model A-3 single punch machine has been fitted with strain and displacement gauges to permit simultaneous recording of several variables including the force exerted by the upper punch, the force exerted on the lower punch, the movement of the upper punch, and the ejection force. Several fields of tablet research which can benefit by the use of this instrument are discussed.
39 citations
TL;DR: Eucalyptus, cinnamon, and origanum red exhibited the greatest antibacterial activity while the volatile oils of cedar wood and myrrh as well as all of the fixed and infused oils were found to possess no activity.
Abstract: The in vitro antibacterial activity of thirty-five volatile oils, five fixed oils, five infused oils, and ninety-five combinations of these oils was ascertained using the filter paper disk method. The oils and oil combinations were tested against five bacteria. Eucalyptus, cinnamon, and origanum red exhibited the greatest antibacterial activity while the volatile oils of cedar wood and myrrh as well as all of the fixed and infused oils were found to possess no activity. The Gram-positive bacteria were more susceptibleto the volatile oils than the Gram-negative. Of the ninety-six combinations of oils only three were found to exhibit greater antibacterial activity as compared with each oil used separately. The three combinations of volatile oils which showed this enhancement of antibacterial activity were: eucalyptus-cinnamondwarf pine needle, eucalyptus-cinnamon-juniper berries, and eucalyptus-cinnamonniaouli. When fixed or infused oils were added to volatile oils the antibacterial activity of the latter was markedly diminished.
38 citations
TL;DR: On the basis of various chemical and genetic studies a scheme of biosynthesis of the compounds found in the mint oil from available species is presented and an arrangement of the mint species themselves on this basis is indicated.
Abstract: On the basis of various chemical and genetic studies a scheme of biosynthesis of the compounds found in the mint oil from available species is presented. The several most interesting species also are classified as either peppermint, spearmint, or acyclic types. A scheme of conversion of the individual ketones within each type is given and an arrangement of the mint species themselves on this basis is indicated.
36 citations
TL;DR: In this paper, metal chelates of isonicotinyl hydrazide (INH) containing divalent copper, cobalt, iron, and zinc and having both 1:1 and 2:1 ratios of INH to metal have been isolated and characterized.
Abstract: Metal chelates of isonicotinyl hydrazide (INH) containing divalent copper, cobalt, iron, and zinc and having both 1:1 and 2:1 ratios of INH to metal have been isolated and characterized. These chelates showed in vivo antitubercular activities in mice comparable to that from INH itself. The 2:1 chelates were found to be considerably more lipophilic (fifty to ninety-fold) than the 1:1 chelates, but underwent conversion to 1:1 chelates at equilibrium. Toxicity determinations on the chelates showed them to resemble the corresponding inorganic salts in their toxic manifestations in mice. These findings suggest that the INH chelates are present mainly as the 1:1 species in vivo , and permit the postulation that INH exerts its antitubercular action as a 1:1 metal chelate.
30 citations
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27 citations
TL;DR: Wescodyne was found to be highly fungicidal and distinctly lethal for tubercle bacilli and the same compound was also effective in moderate concentrations against spores of B. subtilis.
Abstract: Comparative tests were made of the bactericidal and fungicidal activities of an iodophor (Wescodyne®), Roccal®, Amphyl®, and phenol. Roccal was the only germicide in the group that was adversely affected by a synthetic hard water solution. With the exception of phenol, the remaining germicides showed some loss in bactericidal activity when examined in the presence of serum. Wescodyne was found to be highly fungicidal and distinctly lethal for tubercle bacilli. The same compound was also effective in moderate concentrations against spores of B. subtilis
TL;DR: A conventional die constructed with a rectangular hole perpendicular to the axial compression hole in which a third punch was inserted and the necessary mechanical linkages to allow the force appearing on this punch to be transmitted to a force‐measuring transducer was designed and constructed.
Abstract: An apparatus was designed and constructed to measure the pressure transmitted to the die wall during tablet compression Essentially, the apparatus consisted of a conventional die constructed with a rectangular hole perpendicular to the axial compression hole in which a third punch was inserted and the necessary mechanical linkages to allow the force appearing on this punch to be transmitted to a force‐measuring transducer Preliminary compressions were made using sulfathiazole and sodium bicarbonate granulations It was found that in both cases about 30 per cent of the pressure appearing on the punch appeared on the die wall It was also found that magnesium stearate added to the granulations increased the percentage transmitted The implications of these results are discussed
TL;DR: Two recrystallization procedures for the preparation of oxytetracycline and tetracyCline hydrates are described and it is revealed that an increase in solubility of the tetrACYclines is concomitant with a increase in the complexing agent dependency.
Abstract: Oxytetracycline dihydrate and tetracycline trihydrate form soluble complexes with sodium salicylate, sodium parahydroxy benzoate, sodium saccharin, sodium p -amino benzoate, caffeine, and N-methyl pyrrolidone in aqueous solution. In all cases the tetracycline interactions were greater than those with oxytetracycline. With the exception of sodium salicylate at concentrations below 0.5 M, the solubilizing activities of these compounds are roughly in the order listed above. Logarithmic plots show a linear relationship in dilute solution and the slope values of these curves reveal that an increase in solubility of the tetracyclines is concomitant with an increase in the complexing agent dependency. The solubilization may be due, in part, to the presence of strong electronegative centers within the agents used. Two recrystallization procedures for the preparation of oxytetracycline and tetracycline hydrates are described.
TL;DR: Absence of hygroscopic substances appeared to increase the resistance of B. globigii spores to gaseous ethylene oxide sterilization in the presence of glycerin and filter paper.
Abstract: Bacillus globigii spores were exposed to ethylene oxide after being dried on several types of surfaces. The viability tests, after exposure, showed significant effects were produced by the presence of the hygroscopic substances, glycerin, and filter paper. Absence of hygroscopic substances appeared to increase the resistance of B. globigii spores to gaseous ethylene oxide sterilization.
TL;DR: The alkyl sulfate salts of various erythromycin 1 esters were prepared by esterification of erystromycin followed by a double decomposition salt formation and are virtually tasteless and unaffected by mixing with gastric acid.
Abstract: The alkyl sulfate salts of various erythromycin 1 esters were prepared by esterification of erythromycin followed by a double decomposition salt formation. These compounds, and in particular propionyl erythromycin lauryl sulfate, are virtually tasteless and are unaffected by mixing with gastric acid. These properties render them very useful in the preparation of flavored suspensions.
TL;DR: A rapid and specific assay procedure has been developed for the routine determination of apomorphine and the product obeys Beer's law over a wide range of concentration.
Abstract: A rapid and specific assay procedure has been developed for the routine determination of apomorphine. The method involves oxidation of the compound by mercuric chloride and ultraviolet absorption analysis of the extracted reaction product at 330 mμ. The product obeys Beer's law over a wide range of concentration. Optimum conditions for the reaction have been investigated. The method has been applied to the recovery of added apomorphine from aqueous solutions and biological materials. As little as 0.1 mcg. per ml. can be assayed by the procedure.
TL;DR: Much has been written on sampling; however, Grant and the Statistical Research Group (2) summarize sampling developments quite well.
Abstract: Two questions have been asked in regard to sampling for sterility testing: “What size of representative sample should be taken?” and “How much should sample size vary with lot size?” Both of these questions can be answered by using some mathematical calculations together with a few assumptions. Recent developments in sampling theory have shown that sometimes tremendous variations in the quality of lots passed are due to chance alone involved in selecting the sample. It has been shown that it is possible to predict the variations and the frequency with which they will occur. The results of the mathematical calculations on a particular sample plan can be shown graphically by means of a curve called an “operating characteristic curve.” Much has been written on sampling; however, Grant (1) and the Statistical Research Group (2) summarize sampling developments quite well.
TL;DR: Crystalline vitamin B 12 is stable in aqueous solutions of thiamine hydrochloride at pH 3.5 to 4.5 during prolonged storage at room temperature, and the amount of vitamin BI 12 decomposed is shown to be related to the stability of the thiamines.
Abstract: Crystalline vitamin B 12 is stable in aqueous solutions of thiamine hydrochloride at pH 3.5 to 4.5 during prolonged storage at room temperature. Decomposition of vitamin B 12 occurs at elevated temperatures in the presence of thiamine decomposition products or the thiazole moiety. The amount of vitamin BI 12 decomposed is shown to be related to the stability of the thiamine hydrochloride. Crystalline vitamin B 12 is stable in solutions of thiamine hydrochloride and niacinamide at pH 3.5 to 4.5 and in B vitamin solutions at pH 3.0 and 4.5 at normal storage temperatures. Destruction of the vitamin B 12 in these solutions occurs at elevated temperatures.
TL;DR: The results indicate that activated attapulgite and halloysite warrant further investigations as ingredients in intestinal adsorbent preparations.
Abstract: Adsorption studies on strychnine and atropine by activated attapulgite, halloysite, and kaolin have been carried out. The activated attapulgite and halloysite were found to be superior adsorbents to kaolin. The adsorptive properties of the clays were not reduced after they were washed with acid and gastric juice. Activated attapulgite and halloysite had superior adsorptive properties at pH 6.8 and 7.2 than at higher hydrogen-ion concentrations. The results indicate that activated attapulgite and halloysite warrant further investigations as ingredients in intestinal adsorbent preparations.
TL;DR: Preliminary tests in human subjects have indicated that the period of time which tablets coated with styrene-maleic acid copolymer, dibutyl phthalate, and talc resist the stomach contents of human subjects appears to be well predicted by an in vitro test in simulated gastric fluid.
Abstract: Preliminary tests in human subjects have indicated that the period of time which tablets coated with styrene-maleic acid copolymer, dibutyl phthalate, and talc resist the stomach contents of human subjects appears to be well predicted by an in vitro test in simulated gastric fluid U. S. P. Both freshly coated granules and stability samples of tablets coated with this formulation disintegrated rapidly in the small intestine of the dogs and human subjects, respectively. The site of disintegration was the duodenum or jejunum where optimal absorption of many therapeutic agents would be expected.
TL;DR: Activated attapulgite warrants further investigation as an ingredient in intestinal adsorbent preparations after being found to be superior to kaolin and halloysite as adsorbents for Staphyhcoccus aureus.
Abstract: A method for the quantitative determination of the adsorption of bacteria by clays has been described. Studies on the adsorption of four bacteria (all known causative agents in enteric infections) by activated attapulgite, halloysite, and kaolin have been carried out. The four bacteria were Staphyhcoccus aureus, Proteus vulgar is, Salmonella enteritides , and Sbigella paradysenteriae . Activated attapulgite was found to be superior to kaolin and halloysite as adsorbents for Staphyhcoccus aureus. None of the clays was found to be good adsorbents for the other bacteria. The results indicate that activated attapulgite warrants further investigation as an ingredient in intestinal adsorbent preparations.
TL;DR: The mixed mono- and diglycerides have been found to be well absorbed from the intestinal tract, to show no acute toxicity in large doses, and to result in the available tartaric acid being slowly excreted by the kidney.
Abstract: A report is presented on the results of a comparative study of the acute toxicity and the rate of renal excretion of tartaric acid following administration of tartaric acid, diacetyl tartaric acid, and diacetyl tartaric acid esters of mixed mono- and diglycerides obtained from natural fats. The toxicity of the first two compounds has been correlated with their high rate of renal excretion. The mixed mono- and diglycerides have been found to be well absorbed from the intestinal tract, to show no acute toxicity in large doses, and to result in the available tartaric acid being slowly excreted by the kidney.
TL;DR: Evidence was presented to show that tablets which did not disintegrate in one hour by this procedure were not fully available to the body, as judged by the urinary excretion of riboflavin.
Abstract: Rates of urinary excretion of riboflavin were determined after dosing subjects with eight preparations varying in in vitro disintegration time and physiological availability. In vitro disintegration times were determined by the procedure given in U. S. P. XV Second Supplement, modified by the use of thirty minutes time in simulated gastric fluid and by the use of solid disks. Previous work was confirmed and additional evidence presented to show that tablets which did not disintegrate in one hour by this procedure were not fully available to the body, as judged by the urinary excretion of riboflavin. Use of the fluted disks of the existing U. S. P. procedure did not change the relationship between in vivo availability and in vitro disintegration time. The height of riboflavin excretion curves was found to be directly proportional to physiological availability of the riboflavin and was inversely related to in vitro disintegration time. Since rate of urinary excretion has been shown to be directly related to tissue levels for several drugs, it might be expected that marked differences in blood levels of riboflavin would be produced by the various preparations tested.
TL;DR: Results indicate a correlation between percutaneous absorption and the degree of interaction of the polyoxyethylene groups present in the hydrophilic surface-active agents with the salicylates.
Abstract: The effect of the inclusion of several concentrations of surface-active agents in four different types of ointment bases on the percutaneous absorption of salicylic acid and sodium salicylate was determined. Hydrophilic ointment, petrolatum, hydrophilic petrolatum containing water, and polyethylene glycol ointment were modified either by varying the concentration of surface-active agent present in the U. S. P. XV formula, or by adding varying amounts of surface-active agents to those bases in which none was originally present. Sorbitan monostearate, polyoxyethylene 20 sorbitan monostearate, and polyoxyethylene 40 stearate were studied as representative of lipophilic and hydrophilic surface-active agents of the nonionic type. The results indicate a correlation between percutaneous absorption and the degree of interaction of the polyoxyethylene groups present in the hydrophilic surface-active agents with the salicylates.
TL;DR: In this article, a chromatographic method was developed for separating and staining the degradation products of thiamine, and a study of the behavior of this vitamin as a function of pH showed a progressive formation of the carbinol form of Thiamine.
Abstract: A paper chromatographic method was developed for separating and staining the degradation products of thiamine. A study of the behavior of this vitamin as a function of pH showed a progressive formation of the carbinol form of thiamine, thiochrome, probably thiamine disulfide, two pyrimidine derivatives, and two still unknown products. The same method proved satisfactory for the identification and isolation of “glucothiamine”, a product which is formed when thiamine is heated in presence of glucose.
TL;DR: The acidic sapogenin obtained by hydrolysis of the saponin was shown to be hederagenin C 30 H 48 O 4 .
Abstract: A saponin isolated from the alcohol extract of fresh bur clover ( Medicago hispida ) has properties and constants identical with those of hederin. This saponin caused a marked increase in tonus and decreased peristalsis when in contact with isolated strips of rabbit ileum. The acidic sapogenin obtained by hydrolysis of the saponin was shown to be hederagenin C 30 H 48 O 4 .
TL;DR: The azomethine and the component aldehyde, iperonal, were found to have high in vitro fungistatic potency while exhibiting low toxicity in mice.
Abstract: Thirteen azomethines were tested against several pathogenic fungi. The fungistatic activity of the aldehyde constituent was more pronounced than the other components of the azomethines. The azomethine (3,4‐methylenedioxybenzylidene‐4‐carboxyaniline) and the component aldehyde, iperonal, were found to have high in vitro fungistatic potency while exhibiting low toxicity in mice.
TL;DR: Propionyl erythromycin ester lauryl sulfate 3 (PELS) has been found to have very low water solubility and is easily usable in pleasantly flavored suspensions.
Abstract: Clinical usage of erythromycin 1 and propionyl erythromycin ester 2 has confirmed the low toxicity in experimental animals as reported from these laboratories. Propionyl erythromycin ester lauryl sulfate 3 (PELS) has been found to have very low water solubility and is easily usable in pleasantly flavored suspensions. Chronic toxicity studies in rats and dogs have demonstrated the absence of visceral or hematopoietic damage following large doses for over three months. Oral administration of PELS produced higher serum concentrations in rats than propionyl erythromycin. Both antibiotics are mainly absorbed from the intestine of rats and excreted in very small quantities in the bile. High concentrations of erythromycin activity were found in the lung, spleen, liver, kidney, and heart after oral administration. The results of absorption studies using S 35 labeled PELS will be discussed.