Showing papers in "Journal of the American Pharmaceutical Association in 1960"
TL;DR: In this paper, a number of theoretical relations dealing with diffusion through heterogeneous barriers are presented and discussed, which are expected to be useful in predicting barrier behavior in formulations such as pharmaceutical and particularly protective ointments and films.
Abstract: A number of theoretical relations dealing with diffusion through heterogeneous barriers are presented and discussed. These are expected to be useful in predicting barrier behavior in formulations such as pharmaceutical and particularly protective ointments and films. A relationship has been derived which expresses the effective permeability constant, Pm, of a two phase mixture as a function of the volume fraction and the permeability of each phase. The effect of the shape of the particles on Pm is also considered. Where data are available, agreement with theory is satisfactory. The nonstationary state behavior of a two phase heterogeneous barrier is discussed in relation to the diffusion coefficient, partition coefficient, the volume fraction, and the particle size associated with each phase. It is shown that the effectiveness of one heterogeneous barrier may be greater than another for a given time of exposure while for a longer time of exposure the reverse may be the case. The effect of a “skin” or a coat of a third phase on the internal phase particle has also been examined. Finally, the situation in which simultaneous diffusion and absorption occur is discussed and an expression for the lag time has been derived for this case.
147 citations
TL;DR: Vapors of 133 essential oils were screened in vitro for antibacterial activity against six test organisms and one hundred and five vapors were found to possess antibacterial action on at least one of the test organisms as discussed by the authors.
Abstract: Vapors of 133 essential oils were screened in vitro for antibacterial activity against six test organisms. One hundred and five vapors were found to possess antibacterial activity on at least one of the test organisms. Vapors of thyme (white), cassia, thyme (red), savory, cinnamon, origanum, and cherry laurel produced prominent zones of inhibition with all test organisms. Gram-positive bacteria were more susceptible to the vapors than Gram-negative bacteria.
114 citations
TL;DR: The degradation of hydrocortisone phosphate in essentially neutral solutions appears to involve hydrolysis as the only significant degradative pathway and an equation expressing the effect of both temperature and pH on the rate of the reaction is presented.
Abstract: The degradation of hydrocortisone phosphate in essentially neutral solutions appears to involve hydrolysis as the only significant degradative pathway. The reaction is first order with respect to the steroid ester and seems linearly dependent upon the hydrogen ion concentration. The reaction is apparently an unusual 0.44 order with respect to the catalyst. The activation energy for the overall reaction has been found to be 17.0 ± 0.5 Kcal./mole. The “frequency factor” of the Arrhenius equation has been calculated and an equation expressing the effect of both temperature and pH on the rate of the reaction is presented.
91 citations
TL;DR: The properties of amorphous calcium novobiocin in formulation of aqueous suspensions were studied and several distinct steps were identified during the process of reversion.
Abstract: Novobiocin (Cathomycin) is an antibiotic produced in nutrient media by Streptomyces spheroides . Physical characteristics of the amorphous acid form of novobiocin were studied. The amorphous acid is biologically active, but proved metastable in aqueous suspension, reverting on standing to a less soluble, inactive crystal line form. Several distinct steps were identified during the process of reversion; the rate of reversion was found to be temperature dependent. Methods for suppressing crystallization of the amorphous acid are discussed. The properties of amorphous calcium novobiocin in formulation of aqueous suspensions were studied.
86 citations
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78 citations
TL;DR: In this paper, the solubility of benzoic acid was determined in mixtures of several solvents of varying polarity, and the experimental results were compared with the theoretical results as calculated from the Hildebrand equation for regular solutions.
Abstract: The solubility of benzoic acid was determined in mixtures of several solvents of varying polarity. The experimental results were compared with the theoretical solubility as calculated from the Hildebrand equation for regular solutions. The theoretical and experimental results agree well in the region where the solubility parameter of the solute approaches that of the solvent mixture.
47 citations
TL;DR: The use of radioisotopic tracers as a method of stability study was shown to have the advantages of being able to detect the most minute amounts of breakdown products, even in complex mixtures.
Abstract: A method of electrophoretic separation and identification was developed for the products of the thermal degradation of acetylsalicylic acid. The procedure, however, as used in this work was not quantitative. Experiments were performed to determine the progress of the thermally increased hydrolysis of acetylsalicylic acid by means of radioisotope tracer techniques. The use of radioisotopic tracers as a method of stability study was shown to have the advantages of being able to detect the most minute amounts of breakdown products, even in complex mixtures. It is also possible to determine the rate of breakdown without identifying the breakdown products or knowing the mechanism of degradation.
47 citations
TL;DR: The relationships between the chemotherapeutical dosage schedule and the pharmacokinetical constants and the adsorption constants α and β, and the minimum inhibition concentration μ of the bacteriostatic drug are formulated.
Abstract: The relationships between the chemotherapeutical dosage schedule (supporting dose D , ratio of initial to supporting dose D + / D , dosing interval τ ) and the pharmacokinetical constants k 1 , k 2 , and V d , the adsorption constants α and β , and the minimum inhibition concentration μ of the bacteriostatic drug, are formulated.
44 citations
TL;DR: In this article, the first-order rate constants for the decomposition reaction, obtained from the initial rate of formation of 5-hydroxymethylfurfural (5HMF), were consistently higher than those calculated from glucose depletion measurements over long periods of time at temperatures above 100°.
Abstract: The degradation of glucose in acid solution was carried out at various temperatures. The first-order rate constants for the decomposition reaction, obtained from the initial rate of formation of 5-hydroxymethylfurfural (5HMF), were consistently higher than those calculated from glucose depletion measurements over long periods of time at temperatures above 100°. At 100° the rate of formation of 5-HMF increased with time for the early portion of the break-down. The rate constant did not coincide with the Arrhenius plot for higher temperatures. This indicates the possibility of a change of mechanism at lower temperatures. The rate data was fitted to kinetic expressions for first-order consecutive reactions. Agreement between calculated and experimental values indicates that the reaction proceeds by the step-wise mechanism. Data obtained from degradation in varying acid concentrations show that the rate constant does not vary linearly with normality. Decomposition in dioxane-water mixtures indicates that the logarithm of the rate constant varies linearly with the reciprocal of the dielectric constant.
43 citations
TL;DR: A new and rapid method for preparing compressed tablet granulations by the air-suspension technique is discussed and experimental data dealing with material losses and variations in the drug and water content of the prepared granulations are presented.
Abstract: A new and rapid method for preparing compressed tablet granulations by the air-suspension technique is discussed. Experimental data dealing with material losses and variations in the drug and water content of the prepared granulations are presented.
40 citations
TL;DR: Comparative in vitro tests indicate that chlorhexidine has greater antibacterial activity than benzalkonium chloride, a combination of o -phenyl- and p - tert -amyl-phenol, and an iodine-polyvinylpyrrolidone complex under the test conditions.
Abstract: Comparative in vitro tests indicate that chlorhexidine has greater antibacterial activity than benzalkonium chloride, a combination of o -phenyl- and p - tert -amyl-phenol, and an iodine-polyvinylpyrrolidone complex under the test conditions. Chlorhexidine in relatively high dilutions was effective against several cultures of Gram-negative bacteria in the phenol coefficient test. In moderate concentrations, it was active against staphylococci and anaerobes.
TL;DR: Many disposable surgical and pharmaceutical materials are not adequately tested for their toxicity and compatibility with tissues and suggested techniques are described for testing them.
Abstract: Many disposable surgical and pharmaceutical materials are not adequately tested for their toxicity and compatibility with tissues. Suggested techniques are described for testing these items. By the use of such tests the various items available may be checked and a choice made between those which should not be used and those which have been adequately tested and are found to be satisfactory.
TL;DR: The prediction of stability and pharmaceutical formulation of compounds of unknown structure are especially important in the antibiotic age and a mechanism is proposed that accounts for the available data and predicts the properties of degradation intermediates.
Abstract: The prediction of stability and pharmaceutical formulation of compounds of unknown structure are especially important in the antibiotic age. The kinetics of solution degradation of the antibiotic complex of the structurally unknown strepto-varicins are studied spectrophotometrically and equations obtained to characterize degradation as a function of pH. Bioassay has been correlated with spectra and conditions given for maximum stability of assay standards and preservation of yield. A mechanism is proposed that accounts for the available data and predicts the properties of degradation intermediates. The application of an analog computer to kinetic interpretation is given. Kinetic conditions for the differential assay of streptovaricin C were derived.
TL;DR: The results of in vivo experiments gave evidence of a low order of toxicity of Morinda citrifolia root, and it appears that the hypotensor activity resides in the water-soluble fraction of the root of Mor Linda citr ifolia.
Abstract: The results of a study of the anatomy of the stem of Morinda citrifolia L. are described. A preliminary report of the pharmacodynamic study of a 95 per cent alcoholic extract of the root on the isolated uterine horn of an albino rat showed some measure of sedation using doses of 1 to 5,000 to 1 to 36,000. A water decoction of the crude whole root, injected intravenously in the anesthetized dog, in a dose representing 4 Gm. produced a marked lowering of blood pressure which lasted approximately twenty-six minutes. It appears that the hypotensor activity resides in the water-soluble fraction of the root of Morinda citrifolia . The results of in vivo experiments gave evidence of a low order of toxicity of Morinda citrifolia root.
TL;DR: There appears to be correlation between chemical structure and lubricant efficiency in the tablet-die wall system and the effectiveness of fluid-type lubricants seems to be related to the viscosity of the material used.
Abstract: A study of theoretical aspects of tablet lubrication has been carried out in an attempt to elucidate the mechanism of lubricant action and the relationships that exist between chemical structure and lubricating properties. The results of this study indicate that the mechanism of lubricant action, as described for other systems, may be applicable to tablet lubrication. Thus, lubricants may generally be divided into two groups; the first known as fluid- (or hydrodynamic) type which is exemplified by hydrocarbons and the second, termed boundary-type lubricants such as the metallic stearate salts. There appears to be correlation between chemical structure and lubricant efficiency in the tablet-die wall system. The effectiveness of fluid-type lubricants appears to be related to the viscosity of the material used. In this system paraffin was more effective than liquid mineral oil. The evaluation of other classes of compounds revealed that metallic salts of fatty acids were generally the best lubricants while fatty acids, fatty alcohols, alkyl sulfonates, fatty amides, and certain polyvinyl and polyethylene glycol derivatives exhibited good lubricating properties. However, silicone resins, inorganic salts, proteins, carbohydrates, and many metal oxides displayed no lubricating properties. Included in the paper are the results of a survey in which 70 materials were evaluated as tablet lubricants.
TL;DR: Equilibrium dialysis studies utilizing a semipermeable nylon membrane indicate a high degree of association and accompanying inhibition of quaternary ammonium germicides such as cetylpyridinium chloride and benzalkonium chloride with nonionic surfactants such as Tween 80.
Abstract: Equilibrium dialysis studies utilizing a semipermeable nylon membrane indicate a high degree of association and accompanying inhibition of quaternary ammonium germicides such as cetylpyridinium chloride and benzalkonium chloride with nonionic surfactants such as Tween 80. Cetylpyridinium chloride was also found to bind to methylcellulose, but not to PVP or Polyox. Benzalkonium chloride was not bound to methylcellulose, PVP, or Polyox under the conditions of this study.
TL;DR: No significant absorption of sodium salicylate occurred from ointments prepared with petrolatum, hydrophilic petrolatum containing water, or polyethylene glycol ointment, on the basis of saliylate blood levels.
Abstract: An approach to the evaluation of the percutaneous absorption of drugs from ointment bases is described. Salicylic acid and sodium salicylate were selected as test drugs for incorporation into ointment bases representing each of four physical types of ointment vehicles. These ointments were applied to the intact shaved skin of the rabbit and confined by a specially designed bandage. Concentration of salicylate in the blood was determined at hourly intervals following application of the ointment. Salicylic acid was most effectively absorbed from hydrophilic ointment. The extent of absorption from the other ointments studied, in decreasing order, was: hydrophilic petrolatum containing water, petrolatum, and polyethylene glycol ointment. Sodium salicylate was also absorbed to the greatest extent from hydrophilic ointment, although the degree of absorption was considerably less than that observed with salicylic acid. On the basis of salicylate blood levels, no significant absorption of sodium salicylate occurred from ointments prepared with petrolatum, hydrophilic petrolatum containing water, or polyethylene glycol ointment.
TL;DR: The preparation and properties of two new, highly reactive aluminum hydroxide–magnesium carbonate dried gels (AHMC) are described and the rate of reaction with gastric acid is shown to be rapid as well as prolonged in the optimum pH range of 3 to 5.
Abstract: The preparation and properties of two new, highly reactive aluminum hydroxide–magnesium carbonate dried gels (AHMC) are described The rate of reaction with gastric acid is shown to be rapid as well as prolonged in the optimum pH range of 3 to 5 Three methods were used to determine reaction rate including the Reheis and Mutch reaction velocity tests as well as a modified procedure of Holbert, Noble, and Grote An automated apparatus for antacid evaluation is described Data on thirteen antacid chemicals as well as thirty of the most widely used antacids in liquid and tablet form are presented The in vitro antacid properties of AHMC dried gels compares favorably with reactive liquid aluminum hydroxide gel The aging characteristics are shown to be excellent
TL;DR: In this article, the organocadmium reagent was adapted to the synthesis of alkyl β-aminoethyl ketones from β-alanine through the Friedel-Crafts reaction.
Abstract: The organocadmium reagent was adapted to the synthesis of alkyl β-aminoethyl ketones from β-alanine. Some aryl β-aminoethyl ketones were synthesized from β-alanine through the Friedel-Crafts reaction. These two series of β-aminoethyl ketones were proposed as potential antagonists of β-alanine in the metabolism of certain microorganisms. Both the alkyl and aryl β-aminoethyl ketones show antibacterial effect when tested against S. aureus and E. coli in vitro .
TL;DR: A dissolution study was conducted in which the surface area-weight ratio of a dissolving solid was not held constant and cylindrical tablets containing large pores were employed to follow the dissolution process.
Abstract: A dissolution study was conducted in which the surface area-weight ratio of a dissolving solid was not held constant. Cylindrical tablets containing large pores were employed to follow the dissolution process. Studies in distilled water indicated that the surface area of the tablet pore was incompletely exposed to the solvent due to occlusion by air. Solutions with a lower surface tension than water were capable of wetting the entire surface area and a corresponding increase in the dissolution rate was obtained. When the air was evacuated from the artificially produced tablet pores the solvent was permitted to come in contact with the entire surface and the dissolution rate increased. Dissolution from the pore surface occurred at a slower rate than from the exterior surface due to the longer diffusional pathway of the solute molecules.
TL;DR: The “tagged” dye shows promise for locating amyloid and may serve as a means for evaluating drugs for the resorption ofAmyloid, and the method of direct radioiodination is applicable to other similar chemical compounds.
Abstract: Congo red concentrates in amyloid tissue. This study was undertaken to prepare a radioactive congo red which would concentrate in amyloid, permitting external counting and, thereby, scanning and localization, as well as blood concentration measurement. Two methods were used to trace-label the dye to an adequate specific activity for such studies. Injection into guinea pigs with amyloidosis resulting from induced chronic scurvy indicated deposits and radioactivity in the liver and other organs. The “tagged” dye shows promise for locating amyloid and may serve as a means for evaluating drugs for the resorption of amyloid. The method of direct radioiodination is applicable to other similar chemical compounds.
TL;DR: The in vivo metabolism of dextrosulphenidol has been studied using various test organisms and comparisons are made as to the effect of biological variation on the absorption, distribution, and excretion of the drug.
Abstract: The in vivo metabolism of dextrosulphenidol has been studied using various test organisms. Differences are noted and comparisons are made as to the effect of biological variation on the absorption, distribution, and excretion of the drug.
TL;DR: In this article, it has been shown that the time for nonstationary state permeation of these barriers can be significantly increased by the incorporation of small quantities of an active filler into the ointment base.
Abstract: The permeability of protective barriers containing adsorbent type fillers has been studied. It has been shown that the time for the nonstationary state permeation of these barriers can be significantly increased by the incorporation of small quantities of an active filler into the ointment base. The theoretical considerations of permeation through filled ointments have been presented with particular emphasis placed on the theory pertaining to barriers containing a filler with a high affinity for the penetrant. An equation relating the lag time to the concentration and maximum adsorptive capacity of this type filler and to the initial concentration of the chemical agent has been derived and verified by experimental procedures.
TL;DR: Exposure of Penicillium notatum to ionized air reduces the production of penicillin and growth of the mycelium and germination of spores also are depressed, but positive ions exert a greater effect than negative ions on spore germination.
Abstract: Exposure of Penicillium notatum to ionized air reduces the production of penicillin, negative ions exerting a greater effect than positive ions. Growth of the mycelium and germination of spores also are depressed, but positive ions exert a greater effect than negative ions on spore germination. Production of carbon dioxide is depressed to about the same extent as mycelial growth.
TL;DR: A method is given for partially purifying the phenolic components of Cannabis sativa resin and for separating these components by means of paper chromatography.
Abstract: A method is given for partially purifying the phenolic components of Cannabis sativa resin and for separating these components by means of paper chromatography. The application of this method for the preparation of pure cannabinol and tetrahydrocannabinol is described.
TL;DR: In this paper, the absorption spectra of 38 cardiac glycosides, aglycones, and aglycone derivatives, have been determined in sulfuric acid, and the use of these spectra may assist in differentiating between members of the A, B, and C series.
Abstract: The absorption spectra of 38 cardiac glycosides, aglycones, and aglycone derivatives, have been determined in sulfuric acid. The use of these spectra may assist in differentiating between members of the A, B, and C series of digitalis glycosides and aglycones.
TL;DR: Clemizole was highly effective in antagonizing histamine aerosol bronchospasm and enhanced responses to epinephrine appear to be due to a sensitization to this amine by the antihistamine.
Abstract: Experiments have been described which demonstrate effective prolonged antihistaminic activity and other aspects of the pharmacology of clemizole HC1 (1- p -chloro-benzyl-2-pyrrolidyl-methyl-benzimidazole hydrochloride). A relatively high degree of antihistaminic specificity was observed in both in vitro and in vivo experiments. Clemizole was highly effective in antagonizing histamine aerosol bronchospasm. Spontaneous activity of isolated rabbit ileum and intestinal motility in anesthetized dogs were decreased. There was no significant effect on histamine-induced gastric secretion in chronic gastric fistula dogs. Enhanced responses to epinephrine appear to be due to a sensitization to this amine by the antihistamine. Acute and chronic studies showed a relatively low order of toxicity.
TL;DR: It was found that the hydrolysis rate of the ester in the alkali-stable nonionic surfactants varies with the concentration of the surfactant more than with the length of the polyoxyethylene chain of the Surfactant.
Abstract: The effect of surfactants on the rate of hydrolysis of esters, using benzocaine as an example, is reported for a homologous series of alkali-stable nonionic surfactants, and with cationic and anionic surfactants. It was found that the hydrolysis rate of the ester in the alkali-stable nonionic surfactants varies with the concentration of the surfactant more than with the length of the polyoxyethylene chain of the surfactant. Hydrolysis apparently takes place within the micelle, as well as in the aqueous phase. Anionic and cationic surfactants appear to stabilize the drug to base catalysis, resulting in an eighteen-fold increase in half-life in 5 per cent lauryl sulfate solutions. A dilute solution of the quaternary, cetyl trimethyl ammonium bromide, slightly accelerates the rate of hydrolysis.
TL;DR: In this article, it was shown that hydrochlorothiazide can be determined in urine by extracting with ethyl acetate and either reacting directly with chromotropic acid or hydrolyzing first with alkali followed by diazotization and condensation with N-(1-naphthyl)-ethylene diamine hydrochloride.
Abstract: Hydrochlorothiazide may be determined in urine by extracting with ethyl acetate and either reacting directly with chromotropic acid or hydrolyzing first with alkali followed by diazotization and condensation with N-(1-naphthyl)-ethylene diamine hydrochloride.
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