Showing papers in "Journal of the American Pharmaceutical Association in 1956"
TL;DR: Relapse by animals was demonstrated and the importance of the confirmation of the escape training hypothesis was discussed, if this new action reduces the level of withdrawal.
Abstract: Withdrawal has been shown to be a motivating state which may be used to promote learning a new action, if this new action reduces the level of withdrawal. The withdrawal syndrome may be considered a noxious stimulus to which the animal learns an action which reduces the severity of the noxious stimulus. This form of learning is called escape training and is a form of conditioned response. Relapse by animals was demonstrated and the importance of the confirmation of the escape training hypothesis was discussed.
99 citations
TL;DR: It may be concluded that the methyl, ethyl, and propyl esters of p-hydroxybenzoic acid may be used safely as preservatives in effective concentrations for foods and drugs.
Abstract: The results of a study of the acute and chronic toxicity of p-hydroxybenzoic acid and the methyl, ethyl, propyl, and butyl esters in mice, rats, and dogs are presented. All of these compounds possess a low order of acute toxicity. The toxicity of the sodium salts appears to be a function of the length of the alkyl substituent, with the butyl ester about three times as toxic as the methyl ester. The main toxic effect is an acute myocardial depression accompanied by hypotension, but this is transient in nature and not cumulative. No evidence of blood damage or histological changes in tissues of treated animals was noted. In concentrations below 5 per cent, none of the esters produces any evidence of primary irritation when applied to the intact skin of man. From the results obtained, it may be concluded that the methyl, ethyl, and propyl esters of p-hydroxybenzoic acid may be used safely as preservatives in effective concentrations for foods and drugs.
73 citations
TL;DR: Methods for measuring some of the properties of ointments' bases are described, and by such methods commonly used ointment bases are compared.
Abstract: Selection of the base for an ointment should be made only after comparative evaluations of many factors, among which are: (a) drug-release characteristics, (b) consistency and body as defined by viscosity, tube extrusion pressure, penetrometer readings, spreadability, and effect of increased solids, (c) physical and chemical stability, and (d) handling and manufacturing characteristics. Methods for measuring some of these properties are described, and by such methods commonly used ointment bases are compared.
71 citations
TL;DR: The addition of lubricants, e.
Abstract: A study of lubricants during compression and in finished tablets has shown that, (1) lubricants are confined to the surface and intergranular regions of the finished tablets and do not mix intimately with the contents of the granules, (2) approximately 1 per cent lubricant appeared to give nearly o timum granulation lubricity when applied to the test granulations used in this stucfy, (3) fluid lubricants appeared to flow into tablet voids and unlike solid lubricants did not usually cause significant increase in punch forces when added in increasing amounts if the machine settings and weights of die fill were constant, (4) the addition of lubricants, e. g., ma nesium stearate, to granulations tended to roduce slightly softer tablets and at t8e same time significantly prolonged tablet $isintegration time in the usual concentrations.
70 citations
TL;DR: High plasma levels and urinary output of free and conjugated p-hydroxybenzoic acid in dogs indicate that hydrolysis of the ester linkage and metabolic conjugation constitute the chief paths of alteration for all of theEsters studied except the butyl derivative.
Abstract: Free p-hydroxybenzoic acid and its metabolic products in which the phenolic group has not been destroyed bave been determined in tissues and biological fluids of drugs, tablets, and man following the ingestion of the acid and its esters. Recoveries from the urine of animals, regardless of the method of administration, range between 50 and 95 per cent except in the case of butyl esters where the recoveries were approximately 40 per cent. High plasma levels and urinary output of free and conjugated p-hydroxybenzoic acid in dogs indicate that hydrolysis of the ester linkage and metabolic conjugation constitute the chief paths of alteration for all of the esters studied except the butyl derivative. Topical application of ointments containing 10 per cent methyl and 10 per cent propyl p-hydroxybenzoate to the shaved backs of white rabbits produced no irritation during forty-eight hours of contact. Under this condition no drug concentration was detected in the kidneys.
58 citations
TL;DR: Both glucose and insulin in certain doses were found to potentiate and prolong significantly the analgetic action of morphine and probably neither hyperglycemia nor hypoglycemia per se are the direct mechanisms of these effects.
Abstract: A study was made of the effect of glucose and of insulin pretreatment on the analgetic action of morphine in rats as determined by the D'Amour-Smith method. Both glucose and insulin in certain doses were found to potentiate and prolong significantly the analgetic action of morphine. Rats pretreated with 0.6 Gm./Kg. of glucose showed a peak analgetic response 57 per cent greater than their response to morphine alone. Rats pretreated with 0.5 u./Kg. of insulin showed a peak anal-getic response 30 per cent greater than their response to mor hine alone. The potentiation produced by glucose was not proportional to the Z g r e e of hyperglycemia. Probably neither hyperglycemia nor hypoglycemia per se are the direct mechanisms of these effects. Possible mechanisms are discussed.
54 citations
TL;DR: Three formulations were investigated on nine individuals, aged 15-30, to determine their effectiveness as aqueous ophthalmic vehicles for homatropine hydrobromide, and it is believed that the greater effectiveness is probably a result of increased viscosity rather than a lowering of surface tension caused by the methylcellulose.
Abstract: The therapeutic effectiveness of a drug may be profoundly influenced by the vehicle in which it is administered. This is especially true of ophthalmic medication. Three formulations were investigated on nine individuals, aged 15-30, to determine their effectiveness as aqueous ophthalmic vehicles for homatropine hydrobromide. They were identical in electrolyte content, preservative content, and pH, but differed in methylcellulose content. They contained 1 per cent methylcellulose, 0.1 per cent methylcellulose, or no methylcellulose. Homatropine hydrobromide administered in 1 per cent methylcellulose induced greater cydoplegia and mydriasis at almost all doses. It is believed that the greater effectiveness is probably a result of increased viscosity rather than a lowering of surface tension caused by the methylcellulose. The methylcellulose reduced reflex lachrymation and caused no eye irritation or damage. The technique used provides a simple efficient method for further development and testing of new ophthalmic vehicles.
42 citations
TL;DR: The physicochemical procedures for prediction of stability at shelf temperatures by rate studies conducted at elevated temperatures have been applied to the vitamin components of liquid multivitamin' preparations to include statistical techniques and recommendations of concentration adjustment to meet minimum assay specifications of the marketed preparations.
Abstract: The physicochemical procedures for prediction of stability at shelf temperatures by rate studies conducted at elevated temperatures have been applied to the vitamin components of liquid multivitamin' preparations. The procedures have been expanded to include statistical techniques to provide estimates of error in assays, the extent of confidence to be held in prediction, and recommendations of concentration adjustment to meet minimum assay specifications of the marketed preparations. The validity of the predictions and recommendations has been demonstrated by the agreement of classical stability studies on preparations stored at room temperature with the selected values.
41 citations
TL;DR: The water-soluble fraction of the de-alcoholized extract relaxed the intestine and caused negative inotropic action on frog's heart, and anti-epileptic activity was absent.
Abstract: The alcoholic extract of Acorus calamus roots and rhizomes was screened for pharmacological activities. It was found to possess sedative and analgetic proper-ties and caused a moderate depression in the blood pressure and respiration. The water-soluble fraction of the de-alcoholized extract relaxed the intestine and caused negative inotropic action on frog's heart. Anti-epileptic activity was absent.
39 citations
TL;DR: The results show that the several systems behave essentially in the same manner despite the differences in the structures of the polymeric substances.
Abstract: A photometric-titrimetric method and a dialytic method have been employed to obtain information as to the occurrence of complexes in several systems. Interactions of phenol with members of the polyethylene glycol series, with members of the polypropylene glycol series, and with polyvinylpyrrolidone have been studied. The influence on the complexing tendency of reactant concentration, of salt concentration in the system, of alcohol concentration in the system, and of temperature, has been investigated. The results show that the several systems behave essentially in the same manner despite the differences in the structures of the polymeric substances.
37 citations
TL;DR: The results indicate that granulations prepared by the wet granulation method, using starch paste, had approximately 30% void space, while aspirin granulation, prepared byThe slugging process, had about 3% voidspace.
Abstract: A method is presented for determining the porosity of tablet granulations in which two different density measurements are employed. They are (a) the “true” or maximum density of the granules obtained by high pressure compression of samples of the granulations, and (b) the apparent density, determined by mercury displacement. The values resulting from these two measurements on a given granulation were used to calculate the per cent void space in the granules. This report includes data from applying the experimental procedures to four test granulations, potassium bromide crystals (10-20 mesh), and glass beads. The results indicate that granulations prepared by the wet granulation method, using starch paste, had approximately 30% void space, while aspirin granulation, prepared by the slugging process, had approximately 3% void space.
TL;DR: Tests made to determine whether the addition of flavors or varying die method of preparation would improve the disguising power of cocoa syrups showed that ten of the eleven cocoa flavored vehicles prepared were significantly better disguising agents than the official cocoa syrup.
Abstract: Eleven different formulas of cocoa syrup were used to determine statistically which would best mask the taste of quinine hydrochloride. These were compared with cocoa syrup U. S. P., and syrup, U. S. P. Tests made to determine whether the addition of flavors or varying die method of preparation would improve the disguising power of cocoa syrups showed that ten of the eleven cocoa flavored vehicles prepared were significantly better disguising agents than the official cocoa syrup. Three syrups made with Dutch process cocoa showed the highest disguising potentials. All cocoa syrups tested were significantly better disguising agents than syrup, U. S. P
TL;DR: Data are presented for sulfathiazole, sulfapyridine, theophylline, salicylate, penicillin, and tetracycline to illustrate approximate first order drug elimination from the bloodstream.
Abstract: Literature data have been employed to illustrate approximate first order drug elimination from the bloodstream.Data are presented for sulfathiazole, sulfapyridine, theophylline, salicylate, penicillin, and tetracycline.Some interpretations of the possible significance of such drug elimination rate to dosage regimens and dosage form design are discussed.
TL;DR: A new method is proposed for the assay of ipecac which gives results which are appreciably higher than those obtained by the official procedure.
Abstract: A new method is proposed for the assay of ipecac. The alkaloids are extracted, puri-fied, and separated into phenolic and nonphenolic fractions by means of ion exchange resins. The method is simple and gives results which are appreciably higher than those obtained by the official procedure.
TL;DR: A method of analysis for glutethimide and a metabolite, a-phenyl glutarimide is described, based on the formation of a hydroxamic acid derivative which then complexes with ferric ion to give the purple color.
Abstract: A method of analysis for glutethimide and a metabolite, a-phenyl glutarimide is described. It is based on the formation of a hydroxamic acid derivative which then complexes with ferric ion to give the purple color.Doriden was administered orally to dogs and the urinary excretion of free and conjugated glutarimide was studied. The free form proved to be a-phenyl glutarimide and the conjugated form was found to yield a-phenyl glutarimide upon acid hydrolysis.
TL;DR: A reinvestigation and evaluation of the in vitro antibacterial activity of oils (volatile, terpeneless, fixed, and infused) was carried out by using the filter paper disk method.
Abstract: A reinvestigation and evaluation of the in vitro antibacterial activity of oils (volatile, terpeneless, fixed, and infused) was carried out by using the filter paper disk method.The oils were tested against various pathogenic and nonpathogenic Gram-positive and Gram-negative bacteria.
TL;DR: In this paper, a study of the chemical kinetics of the hydroxyl ion catalyzed hydrolysis of atropine in solution has been carried out, and the mechanism of this hydrolyisation has been shown to consist of two reactions, the effect of each being governed by the hydoxyl ion concentration.
Abstract: A study has been carried out on the chemical kinetics of the hydroxyl ion catalyzed hydrolysis of atropine in solution. The mechanism of this hydrolysis has been shown to consist of two reactions, the effect of each being governed by the hydroxyl ion concentration. The temperature dependency of each reaction has been established, and equations have been proposed which enable the approximation of the half-life of atropine undergoing hydrolysis at constant temperature and constant hydroxyl ion concentration. Half-life values calculated by these equations have been shown to compare favorably with those obtained experimentally.
TL;DR: It wasserved that a fluorescent, greenish-yellow color was obtained by treating an alcoholic solution of reserpine with dilute sulfuric acid and sodium nitrite, and this reaction has been adapted to the quantitative determination of Reserpine.
Abstract: A rapid and specific method for the analysis of reserpine was needed. It was ob-served that a fluorescent, greenish-yellow color was obtained by treating an alcoholic solution of reserpine with dilute sulfuric acid and sodium nitrite. This reaction has been adapted to the quantitative determination of reserpine. The method is applicable to the determination of reserpine in tablets, solutions, and elixirs. Similar alkaloids such as alstonine, rauwolscine, sarpagine, raunescine, deserpidine, and yohimbine do not interfere.
TL;DR: A new apparatus which measures resistance to abrasion and shock has been designed and has been found useful for the control of plain, compressed tablets, and especially for evaluating new formulations.
Abstract: Breakage of medicinal tablets is a source of complaint and is an economic waste. It is desirable, therefore, to formulate and produce tablets which will survive handling in production and in distribution. Estimation of the ability of tablets to survive such handling has been difficult because of the lack of an adequate test to measure the property. A new apparatus which measures resistance to abrasion and shock has been designed. A weighed sample of tablets is subjected in the apparatus to a tumbling action and to the shock resulting from a free-fall of six inches. The loss of weight suffered is a measure of the friability of the tablets. The test has been found useful for the control of plain, compressed tablets, and especially for evaluating new formulations.
TL;DR: In vivo rabbit corneal tests along with improved techniques of invitro testing indicate that bactericidal concentrations of preservatives are required for maximum safety in ophthalmic solutions.
Abstract: The criteria of sterility of ophthalmic solutions has been based on in vitro bacterio-logical studies In vivo rabbit corneal tests along with improved techniques of invitro testing indicate that bactericidal concentrations of preservatives are requiredfor maximum safety Polymyxin B sulfate is the agent of choice
TL;DR: From l-cycloheptyl-2-aminoethane the corresponding N-methyl and N,N-dimethyl derivatives were synthesized and by simple operations, primary, secondary and tertiary aminopropanes were obtained.
Abstract: A number of cycloalkylacetones were prepared by treatment of a cydoalkylacetyl chloride with dimethylcadmium. The acetones were converted into formamido derivatives from which, by simple operations, primary, secondary and tertiary aminopropanes were obtained. From l-cycloheptyl-2-aminoethane the corresponding N-methyl and N,N-dimethyl derivatives were synthesized.
TL;DR: This study deals with the relationship of sulfadiazine sodium solubility with the hydrogen ion concentration in several solvent systems which have been employed in injectable products.
Abstract: An investigation was conducted to stabilize sulfadiazine sodium injection when exposed to various storage conditions. Prolonged storage of sulfadiazine sodium injection U. S. P. has been known to result in coloration due to oxidation and formation of a precipitate. This study deals with the relationship of sulfadiazine sodium solubility with the hydrogen ion concentration in several solvent systems which have been employed in injectable products. Solubility curves were determined for a number of solvents and from these results their usefulness was ascertained.
TL;DR: Reserpine can be incorporated into tablet coatings when direct combination with other active ingredients causes incompatibility, assay difficulty, or when the reserpine is needed immediately and the other ingredients are better released later.
Abstract: Results are presented of long‐term formulation and stability studies of reserpine. Procedures are described for the preparation of capsules, compressed tablets, injections, and an elixir of reserpine. Compressed tablets may be prepared either by double compression or by wet granulation. Acacia, gelatin, dextrose, sucrose, lactose, starch, dicalcium phosphate, and Carbowax 4000 and 6000 are compatible with reserpine. Magnesium stearate, calcium stearate, and talc have also been used in tablet and capsule formulations with no adverse effect on reserpine. Citric acid, tartaric acid, acetic acid, alcohol, benzyl alcohol, Tween 80, polyethylene glycol 300, and propylene glycol generally are satisfactory solvents or cosolubilizers in elixirs and injections. Reserpine can be incorporated into tablet coatings when direct combination with other active ingredients causes incompatibility, assay difficulty, or when the reserpine is needed immediately and the other ingredients are better released later. Reserpine is compatible with phenobarbital, veratrum viride, amphetamine sulfate, methyl testosterone, hyoscyamine sulfate, atropine sulfate, and niacinamide. Reserpine solutions in clear glass bottles exposed to diffuse light lost potency. Sensitivity to ultraviolet light is best prevented by storage in amber glassware.
TL;DR: The stability of vitamin B 12 concentrates appears to be related directly to the concentration of cyanocobalamin present in the concentrate, which is markedly more stable than cyanide‐free B 12 analogs in ascorbate solutions.
Abstract: The stability of eight vitamin B 12 products in 1% ascorbic acid solution in 1 molar acetate buffer at p H 4.0 has been studied during storage at constant temperatures. Cyanocobalamin (crystalline vitamin B 12 ) was shown to be markedly more stable than cyanide‐free B 12 analogs in ascorbate solutions. Vitamin B 12 concentrates containing mixtures of cyanocobalamin and noncyano analogs were found to be less stable in ascorbate solution than concentrates containing cyanocobalamin exclusively. The stability of vitamin B 12 concentrates thus appears to be related directly to the concentration of cyanocobalamin present in the concentrate.
TL;DR: In this paper, the isolation and characterization of a toxic principle from Acacia berlandieri is described and the compound was identified as N-methyl β-phenylethylamine.
Abstract: The isolation and characterization of a toxic principle from Acacia berlandieri is described. The compound was identified as N-methyl β-phenylethylamine.
TL;DR: High pressure was used in the Kolbe synthesis of aromatic hydroxy acids with Schmitt's modification for synthesizing the salicylic acid from sodium phenolate and carbon dioxide at 110-140°.
Abstract: The historical Kolbe synthesis of aromatic hydroxy acids with Schmitt's modification for synthesizing the salicylic acid from sodium phenolate and carbon dioxide at 110-140°; and high pressure was used in this method of synthesizing the Cu carboxyl salicylic acid followed by acetylization to C 14 carboxyl acetylsalicylic add.
TL;DR: The results lend support to the hypothesis that flexibility per se is a factor to be considered in the collation of chemical structure with pharmacologic activity.
Abstract: Cyclic compounds which imitate two spatial configurations of acetylcholine have been studied as to their muscarinic activities and hydrolyzability by acetylcholinesterase. The results lend support to the hypothesis that flexibility per se is a factor to be considered in the collation of chemical structure with pharmacologic activity.
TL;DR: A study of the tetracaine hydrochloride-caffeine system has shown that the hydro-lytic rate of the ester component is reduced in the presence of the xanthine in a manner similar to that of the benzocaine- caffeine and the procaine hydro chloride-Caffeine systems.
Abstract: A study of the tetracaine hydrochloride-caffeine system has shown that the hydro-lytic rate of the ester component is reduced in the presence of the xanthine in a manner similar to that of the benzocaine-caffeine and the procaine hydrochloride-caffeine systems. Evidence seems to indicate however, that the stoichiometry of the complexing reaction is different from the previous cases. The data obtained are best rationalized on the basis that tetracaine ion forms two types of complexes in solution, the first consisting of two caffeine molecules to one tetracaine ion and the second of two tetracaine ions to one caffeine molecule. According to the present findings, addition of one-half per cent caffeine to a similar concentration of tetracaine hydro-chloride in water, for example, reduces the hydrolytic rate by thirty-five per cent. In the presence of two per cent caffeine, the rate of hydrolysis is only one-third that of the caffeine-free solution.
TL;DR: The ionization constants, solubilities, and relative surface activities of sixteen com-mercially available antihistaminics are reported and theAntihistaminic effect is reviewed and discussed in the light of these properties.
Abstract: The ionization constants, solubilities, and relative surface activities of sixteen com-mercially available antihistaminics are reported. The antihistaminic effect is reviewed and discussed in the light of these properties. The usefulness of solubility as an indicator of toxicity, duration of effect, and local anesthetic potency is emphasized.
TL;DR: The rate of destruction of crystalline vitamin Bu in neutral aqueous solutions, when exposed to direct sunlight, indirect sunlight, dim daylight, artificial light, ultraviolet light, and various monochromatic light sources has been determined.
Abstract: The rate of destruction of crystalline vitamin Bu in neutral aqueous solutions, when exposed to direct sunlight, indirect sunlight, dim daylight, artificial light, ultraviolet light, and various monochromatic light sources has been determined. Sunlight, at a brightness of 8,000 foot-candles, causes a ten per cent loss for each half hour of ex-posure. Below 300 foot-candles, no destruction is noticeable. Artificial light of about 14,000 foot-candles causes a loss of about twelve per cent per half hour. A brightness of 3,600 foot-candles causes no alteration after two hours. With ultraviolet light the pattern of destruction is similar to that obtained with sunlight. For monochromatic light sources, photolysis is higher in the short wave length region. No destruction was observed in the red.