Showing papers in "Journal of the American Pharmaceutical Association in 1958"
TL;DR: Numerous powdered vegetable drugs and some powdered animal drugs were examined under ultraviolet radiation after treatment with several reagents and the characteristic fluorescence of each drug was observed and data pertaining to color and intensity were recorded.
Abstract: Numerous powdered vegetable drugs and some powdered animal drugs were examined under ultraviolet radiation after treatment with several reagents. The reagents were 1 N sodium hydroxide in methanol, 1 N sodium hydroxide in water, 1 N hydrochloric acid, nitric acid diluted with an equal volume of water, and sulfuric acid diluted with an equal volume of water. The characteristic fluorescence of each drug was observed and data pertaining to color and intensity were recorded.
328 citations
TL;DR: The decomposition of aspirin in the solid state has been demonstrated to be dependent on vapor pressure and temperature as discussed by the authors, and a possible mechanism of decomposition is offered, which consists of an initial sorption of a water layer by each particle, diffusion of aspirin into solution, and decomposition taking place by acid catalyzed hydrolysis.
Abstract: The decomposition of aspirin in the solid state has been demonstrated to be dependent on vapor pressure and temperature A possible mechanism of decomposition is offered, which consists of an initial sorption of a water layer by each particle, diffusion of aspirin into solution, and decomposition taking place by acid catalyzed hydrolysis A series of equations which describe the mechanism have been derived and the experimental data demonstrated to fit them Using these equations, the various kinetic constants have been determined
100 citations
TL;DR: It is suggested that perfume oils be incorporated more widely into common toilet articles applied to the body surfaces as well as medicaments used externally.
Abstract: One hundred perfume oils were tested for antimicrobial properties against a series of pathogenic and nonpathogenic bacteria and fungi. The in vitro filter paper disk method was used exclusively for testing activity. The perfume oils were found to possess remarkable antimicrobial properties with greater activity against fungi than against bacteria. It is suggested that perfume oils be incorporated more widely into common toilet articles applied to the body surfaces as well as medicaments used externally.
91 citations
TL;DR: In this article, the chemistry of the formation of various species of titrable iodide in solutions of elemental iodine and iodide is described in a quantitative manner, and equations are given for computing the cysticidal residual I 2 with a given contact time, and vice versa, at varying temperatures.
Abstract: The chemistry of the formation of various species of titrable iodine in solutions of elemental iodine and iodide are described in a quantitative manner. The relative cysticidal efficiencies of various species of titrable iodine and the effect of temperature on cysticidal efficiency of I 2 are described, and equations are given for computing the cysticidal residual I 2 with a given contact time, and vice versa, at varying temperatures, as well as that for computing the cysticidal residual iodine in I 2 -I-3 systems. The relative viricidal (against Coxsackie B2 virus) efficiencies of various species of titrable iodine and the effect of temperature on viricidal efficiency of I 2 are described, and the employment of the equations used in computing the cysticidal residual iodine for I 2 and I 2 I- 3 combination, with or without modification, are given. Because of the incompleteness of the data other than those on I 2 at 25deg;, values obtained in various computations are presented with reservation but are considered as relatively safe for use in practice. The use of preparations of iodine for water disinfection in practice is discussed.
59 citations
TL;DR: It was found that the rates of dissolution in varying concentrations of sodium chloride in neutral solutions can be largely explained by the salting out effects of the electrolyte.
Abstract: A theory is presented which describes the rate of dissolution of solids in basic and buffered media. The formulation is based on the Nernst-Brunner film model assuming a solution diffusion controlled process. Useful expressions are obtained which give relative dissolution rates as functions of the primary variables. Results of calculations predict that for a solid weak acid dissolving in an aqueous basic solution, the rates of dissolution become essentially independent of the strength of the base above certain values. In the region where it is independent of the base strength the rate is a linear function of the product of the base concentration and the base diffusion coefficient. The theoretical conclusions are satisfactorily substantiated by experiments on the rates of dissolution of benzoic acid in basic media of varying strength and diffusivities. The following bases were used as additives: sodium hydroxide, sodium bicarbonate, sodium tetraborate, disodium phosphate, sodium acetate, and ethanolamine. Studies were also carried out with added swamping electrolyte. It was found that the rates of dissolution in varying concentrations of sodium chloride in neutral solutions can be largely explained by the salting out effects of the electrolyte.
55 citations
TL;DR: The effect of propylene glycol in counteracting the gel point depression caused by magnesium chloride or sucrose as examples of electrolytes and nonionic hydrophilic compounds, respectively, is illustrated.
Abstract: The effect of certain additives on the gel point of various grades of Methocel 4000 solutions has been investigated. Most electrolytes, as well as sorbitol, sucrose, and glycerin depress the gel point while ethanol, propylene glycol, and polyethylene glycol 400 raise the gel point. The effect of propylene glycol in counteracting the gel point depression caused by magnesium chloride or sucrose as examples of electrolytes and nonionic hydrophilic compounds, respectively, is illustrated. The gel point raising effect of ethanol, propylene glycol, and polyethylene glycol 400 has been related to their solvent properties.
51 citations
TL;DR: A majority of the compounds investigated showed a progressive loss of antifungal activity with increasing pH values to the point that some were totally ineffective in the neutral and alkaline range.
Abstract: Twelve compounds having antifungal activity were investigated at pH levels of 3, 5, 7, and 9 for the effects of pH changes on their relative efficacy against four common mold contaminants. Tests conducted utilized standardized spore suspensions planted on sterile slants of a modified Sabouraud's agar medium containing graded amounts of the antifungal compounds. A majority of the compounds investigated showed a progressive loss of antifungal activity with increasing pH values to the point that some were totally ineffective in the neutral and alkaline range.
40 citations
38 citations
TL;DR: In this paper, a reproducible composition of tannates containing one part of amine for each galloylgallic acid moiety of Tannic acid is presented.
Abstract: Tannates of several therapeutic amines have been prepared and shown to be reproducible compositions containing one part of amine for each galloylgallic acid moiety of tannic acid. Dialysis experiments were conducted to determine the influence of a number of factors on the rate of release of diffusible amine from the relatively insoluble complex. In the presence of aqueous solutions of electrolytes amines are slowly released from their tannates and the rate increases with the [H + ]. Polygalacturonic acid can reduce the rate of release of free amine from the tannate, particularly at lower pH. The application of these principles to the preparation of oral repository forms of therapeutic amines is discussed.
31 citations
TL;DR: The results suggested that the destruction of prednisolone in aqueous alkali resulted from at least three parallel pseudo first-order reactions.
Abstract: The rate of disappearance of the dihydroxyacetone function of prednisolone was studied in homogenous alkaline solution. The degradation of prednisolone exhibited a first-order dependency on the steroid concentration and occurred with the concomitant appearance of acidic and neutral steroidal products. The exclusion of air from the system was found to decrease the rate of degradation. This slowing of the rate was apparently due to the elimination of an oxygen-dependent reaction which normally formed an acidic steroidal product. The results suggested that the destruction of prednisolone in aqueous alkali resulted from at least three parallel pseudo first-order reactions. The hydroxide-ion dependencies of the reactions were investigated and the hydroxide-ion catalytic constants were estimated.
30 citations
TL;DR: Experimental results on three radio iodide-131 tagged compounds are presented and appear to confirm the resulting pseudo-first order rate equation.
Abstract: The details of a radiological procedure are presented by which it is possible to conduct continuous external detection of the rate of rectal absorption of radio-tagged compounds specially designed suppository vehicles inserted in the rectal passage of a female rat. An analysis of the rate data is presented and a mathematical expression is derived which corrects the activity detected by the counter for the effect of the diffusion of the drug within the vehicle and for the accumulation of the absorbed drug in the scanned volume segment of the animal. Experimental results on three radio iodide-131 tagged compounds are presented and appear to confirm the resulting pseudo-first order rate equation.
TL;DR: Zein, with and without certain additives, was added to isopropyl alcohol to coat tablets that adequately withstand heat, abrasion, and humidity.
Abstract: Zein, with and without certain additives, was added to isopropyl alcohol. Tablets coated with the resultant nonenteric fluids adequately withstand heat, abrasion, and humidity. Tastes and odors of the original tablets are concealed by the coating. Grooves and emblems on the tablet surface are retained and remain visible through the coating. The differences in solubility between the coated and uncoated tablets are negligible.
TL;DR: In this paper, the formation of 5-hydroxymethylfurfural from glucose was subject to general acid-base catalysis and the rate of reaction was inversely proportional to the initial concentration of glucose.
Abstract: Glucose solutions were thermally decomposed under varying conditions. Preliminary findings showed that the formation of 5-hydroxymethylfurfural from glucose was subject to general acid-base catalysis. Results also indicate that the rate of reaction was inversely proportional to the initial concentration of glucose.
TL;DR: Chromatographic examination of the urine of two human volunteers before and after the ingestion of 2 grams of dihydroquercetin demonstrated the conversion of the compound to 3,4-dihydroxyphenyl-acetic, m -hydroxymhenylACetic, and 3-methoxy-4-hydroxylacetic acids.
Abstract: Dihydroquercetin, which is closely related to quercetin in chemical structure, has been shown to be nontoxic when fed to albino rats at a dietary level of 1 per cent for long periods of time. Chromatographic examination of the urine of two human volunteers before and after the ingestion of 2 grams of dihydroquercetin demonstrated the conversion of the compound to 3,4-dihydroxyphenyl-acetic, m -hydroxyphenylacetic, and 3-methoxy-4-hydroxyphenylacetic acids. These same metabolites are excreted following oral administration of quercetin, or DOPA, to rats, rabbits, or humans.
TL;DR: The rectal absorption rates of sodium iodide and the sodium salt of 2,4,6-triiodophenol in suppository bases at various pH values and in the presence of surface-active agents and polyethylene glycol additives were determined by continuous external detection at the site of insertion.
Abstract: The rectal absorption rates of sodium iodide and the sodium salt of 2,4,6-triiodophenol in suppository bases at various pH values and in the presence of surface-active agents and polyethylene glycol additives were determined by continuous external detection at the site of insertion. The rate of sodium iodide absorption is accelerated in the presence of surfactants and appears to be proportional to the surface tension lowering and the peptizing action of their surface active components. The rate of absorption of the phenolate is retarded by the presence of surfactants. Hydrolysis and subsequent solubilization of the free phenol is postulated to explain this effect.
TL;DR: First order analysis of the results indicated that the drugs are best absorbed from true solutions in water, or from water suspensions of the drug.
Abstract: A study of the rectal absorption of iodide-131 tagged iodoform and 2,4,6-triiodo-phenol, at pH's where the drug is undissociated, was carried out in liquid semi-aqueous isotonic vehicles containing the drug in suspension, in true solution, and in solution in surfactant micelles. First order analysis of the results indicated that the drugs are best absorbed from true solutions in water, or from water suspensions of the drug. Surface-active agents and polyoxyethylene polymers markedly retard the rate of absorption. The relative particle size of the suspended drug influenced the absorption rate. Solution of the drugs in solid polyethylene glycol and oleaginous bases resulted in very prolonged absorption times. Head count studies (simulating continuous blood level studies) and the data on the tissue distribution of the compounds are also presented.
TL;DR: The initial increase in low-frequency electroshock seizure threshold, induced by a single large dose of ethanol, was followed by a significant decrease, indicating that the central nervous system tends rapidly to accommodate to the ethanol milieu so that the electro shock seizure threshold does not exactly parallel the plasma ethanol concentration.
Abstract: Ethanol was found to exhibit anticonvulsant activity in nontoxic doses as measured by four of six well-standardized methods. The effective dose of ethanol, as determined by the various tests, was found to be linearly related to its plasma concentration. The initial increase in low-frequency electroshock seizure threshold, induced by a single large dose of ethanol, was followed by a significant decrease. The central nervous system tends rapidly to accommodate to the ethanol milieu so that the electroshock seizure threshold does not exactly parallel the plasma ethanol concentration. The significance of these observations is discussed.
TL;DR: Blood bromide concentrations in rabbits and dogs were found to be elevated following discontinuance of bromides, not only in animals receiving chloride, but also in controls.
Abstract: Blood bromide concentrations in rabbits and dogs were found to be elevated following discontinuance of bromide, not only in animals receiving chloride, but also in controls. Elevation of the blood bromide level in controls was significantly greater than the elevation observed in those receiving chloride. Fluctuations in bromide levels during excretion are taken as evidence that bromide toxicity is related to total bromide extracellular retention rather than simply to blood chloride replacement.
TL;DR: The technique of solvent blending by manipulation of dielectric constants may be summarized as follows: from the literature or experiment determine a single solvent for the concentration desired; determine the Dielectric constant of the single solvent; assemble those solvents, chosen as applicable, that are soluble or miscible among themselves; and use alligation to determine the percentages of Solvents required to produce the desired approximate dielectrics as mentioned in this paper.
Abstract: The technique of solvent blending by manipulation of dielectric constants may be summarized as follows: from the literature or experiment determine a single solvent for the concentration desired; determine the dielectric constant of the single solvent; assemble those solvents, chosen as applicable, that are soluble or miscible among themselves; and use alligation to determine the percentages of solvents required to produce the desired approximate dielectric constant.
TL;DR: The results indicate that the most practical formulation for delayed absorption is 300,000 units of small particle procaine penicillin G per cc.
Abstract: Serum concentrations in rabbits following intramuscular injection of numerous suspensions of procaine penicillin G in various vehicles have been presented. The effects of the nature of the vehicle and the particle size of the procaine penicillin G have been studied. The results indicate that the most practical formulation for delayed absorption is 300,000 units of small particle (less than 5/μ) procaine penicillin G per cc. of peanut oil or sesame oil gelled with 2% aluminum monpstearate. Extensive data in human subjects are submitted to corroborate the animal results.
TL;DR: In this paper, the authors discuss the difficulties inherent in treating problems associated with formulations of concentrated pharmaceutical suspensions from the standpoint of a physical chemist and propose a new equation which may be more valid for heterogeneous, irregular particles than the classical Stoke's formula.
Abstract: Difficulties inherent in treating problems associated with formulations of concentrated pharmaceutical suspensions are discussed from the standpoint of a physical chemist. Relationships which determine settling and creaming rates are treated in some detail, a new equation being proposed which may be more valid for hetero-dispersed, irregular particles than the classical Stoke's formula. Factors which influence crystal growth and caking are also discussed. Some reference is also made to diffusional processes of pharmaceutical importance.
TL;DR: In this article, a series of 3-n-aliphatic substituted pyrazoles have been shown to have anticonvulsant activity in rats and mice and they were found to be more active in rats than in mice.
Abstract: Pyrazole and a series of 3-n-aliphatic substituted pyrazoles have been shown to have anticonvulsant activity in rats and mice. In this study, extension of the length of the aliphatic chain up to four carbons increased the acute toxicity and anticonvulsant activity of these compounds. Further lengthening of the substituents decreased the toxicity and activity. The compounds, as anticonvulsants, were found to be more active in rats than in mice.
TL;DR: The effects of aqueous suspensions of a number of solid buffers on prednisolone at 37.5° have been determined and magnesium oxide suspensions produced a first-order degradation of the steroid side-chain to the etio acid.
Abstract: The effects of aqueous suspensions of a number of solid buffers on prednisolone at 37.5° have been determined. The steroid was adsorbed by magnesium trisilicate according to the Freundlich relationship. Magnesium oxide suspensions produced a first-order degradation of the steroid side-chain to the etio acid. Aluminum hydroxide, calcium carbonate, and magnesium carbonate were without effect.
TL;DR: Acute toxicity studies on N-acetyl- p -aminophenol (NAPAP), salicylamide (SAM), and acetylsalicylic acid (ASA) revealed that NAPAP was least toxic in rats and guinea pigs while SAM was least Toxic in mice.
Abstract: Acute toxicity studies on N-acetyl- p -aminophenol (NAPAP), salicylamide (SAM), and acetylsalicylic acid (ASA) revealed that NAPAP was least toxic (LD S o) in rats and guinea pigs while SAM was least toxic in mice. As antipyretic agents NAPAP and ASA were approximately equivalent in potency and both were more effective than SAM. A consideration of the ratio of the minimum neurological deficit doseio (TDso) and the minimum effective antipyretic dose indicated that NAPAP and ASA had a wider safety margin than SAM. ASA produced tachycardia, pyrexia, polypnea, and an increase in tidal volume. NAPAP and SAM produced little change in blood pH, tidal volume, respiratory rate, and heart rate. Myocardial depression was seen with ASA and SAM but not with NAPAP.
TL;DR: Extent and type of thixotropic breakdown in aqueous, paste-like, procaine penicillin G preparations designed for intramuscular injection have been measured.
Abstract: Extent and type of thixotropic breakdown in aqueous, paste-like, procaine penicillin G preparations designed for intramuscular injection have been measured. The rheological properties of such suspensions are correlated with surface area and particle size distribution of the constituent powders. Certain thixotropic parameters of repository preparations are related to the nature of the depots formed in rabbit muscle and with product injectability and effectiveness in the human, as revealed by blood level data. A dilute gelatin gel has been found useful in forecasting and illustrating the nature of depots formed in muscle tissue.
TL;DR: Aluminum ion is bound to human keratinous materials and the carboxylate groups of the protein are probably the primary sites of aluminum sorption.
Abstract: Aluminum ion is bound to human keratinous materials. Aluminum interaction with (guinea pig) epidermis is strongly dependent upon pH. The carboxylate groups of the protein are probably the primary sites of aluminum sorption.
TL;DR: Change in optical rotation and in chemical activity upon storage at 80° in sealed, evacuated ampuls has been studied with various buffer systems at different pH values and with different concentrations of reactants.
Abstract: Degradation of epinephrine solutions stored in an oxygen free atmosphere in the presence of as little as 0.1 per cent bisulfite occurs at faster rates than in complete absence of bisulfite. Loss of epinephrine chemical activity as determined by the triacetyl derivative procedure occurs with concomitant bisulfite loss. Change in optical rotation and in chemical activity upon storage at 80° in sealed, evacuated ampuls has been studied with various buffer systems at different pH values and with different concentrations of reactants. An inactive degradation product has been isolated and partly characterized.
TL;DR: The method of determining durability of tablets was devised for this study, while the other methods used were standard procedures and indicated that some measurable effects can be noted.
Abstract: A series of six formulations was made in which the amount of lubricant added was a variable ranging from 0 to 5 per cent, and in which the amount of fines added was a variable ranging from 0 to 70 per cent. The rate of flow was measured, using a standard procedure which was modified for this experiment. A measurable effect was induced by the lubricant and the fines. The study was extended to determine whether the effects of lubricant and of fines could be demonstrated in the actual compression of the tablet. The results obtained indicate that some measurable effects can be noted. The physical properties evaluated were: weight variation, hardness, thickness, disintegration, and durability. The method of determining durability of tablets was devised for this study, while the other methods used were standard procedures.
TL;DR: A method for the determination of vitamin D applicable to pharmaceutical products is described in detail, using acetic anhydride which inhibits completely and selectively the vitamin D-SbCl 3 reaction, providing a reaction blank that greatly improves the specificity of the reaction.
Abstract: A method for the determination of vitamin D applicable to pharmaceutical products is described in detail. The method involves saponification, extraction, chromatography, and color measurement by a modified antimony trichloride test. An important feature is the use of acetic anhydride which inhibits completely and selectively the vitamin D-SbCl 3 reaction, providing a reaction blank that greatly improves the specificity of the reaction. Of particular concern are the purity of color reagent, and the adsorption index of the magnesium oxide and alumina adsorbents used in the chromatography. Data are presented showing stability of vitamin D in the chromatography, the effect of acetic anhydride in the color reaction, and the validity of corrections based upon the acetic anhydride blank, and upon absorption differences at 500 and 550 mμ wavelengths. The character of the vitamin A degradation interferences is discussed and analytical results of the method applied to a series of pharmaceutical products are compared with bioassay values.