RESUMEN
Bioavailability of chloramphenicol pharmaceutical forms prepared with the use of antibiotic substances differing in their dispersion levels was studied. It was shown that the level and rate of the drug absorption into blood did not always depend on the size of the substance particles. Fine crystalline substances of the antibiotic manufactured by two firms almost not differing in their dispersion levels markedly differed in the rate of antibiotic transfer into solution and the level of its blood absorption in humans. Tablets prepared with the use of the above substances were also characterized by various bioavailability levels. Study of the dissolution rate of separate fractions of the same substance revealed dependence of this parameter on the particle size.
Asunto(s)
Cloranfenicol/metabolismo , Administración Oral , Disponibilidad Biológica , Cloranfenicol/administración & dosificación , Cloranfenicol/sangre , Humanos , Absorción Intestinal , Tamaño de la Partícula , Polvos , ComprimidosRESUMEN
Bioavailability of methacycline capsules manufactured by two different firms was studied and it was shown that they had statistically significant differences. Conditions for investigation of the rate of methacycline transfer from the pharmaceutical form into solution were developed with the use of a "rotating basket". Such investigations provided in vitro prediction of the drug bioavailability. The effect of additives on bioavailability of methacycline capsules was found. Study of bioavailability of doxycycline capsules manufactured by the same two firms revealed no differences.
Asunto(s)
Doxiciclina/metabolismo , Metaciclina/metabolismo , Absorción , Administración Oral , Adulto , Animales , Disponibilidad Biológica , Cápsulas , Doxiciclina/administración & dosificación , Humanos , Metaciclina/administración & dosificación , Tamaño de la Partícula , Polvos , Conejos , Solubilidad , Factores de TiempoRESUMEN
The main principles in preparation of national standards of the antibiotics manufacture in the USSR are compared with those of the World Health Organization. The characteristics of preparing standards of mono- and multicomponent antibiotics, as well as the requirements for optimal packing of the standards are presented.
Asunto(s)
Antibacterianos/normas , Antibacterianos/farmacología , Fenómenos Químicos , Química Física , Difusión , Relación Dosis-Respuesta a Droga , Estándares de Referencia , U.R.S.S. , Organización Mundial de la SaludRESUMEN
Optimal conditions for separation of rifampicin in a thin layer of a sorbent were developed. This allowed one to study the quantitative content of the admixtures of the related substances in the eluates of the respective spots on chromatograms. The possible use of both the spectrophotometric method and the biological agar diffusion method for testing the eluates was shown. The method of phase solubility also provided objective characterization of the purity levels of market rifampicin. A significant increase in the level of the admixtures of the related substances in rifampicin in 150 mg capsules was found on their storage.
Asunto(s)
Contaminación de Medicamentos , Rifampin/análisis , Cápsulas , Cromatografía en Capa Delgada/métodos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Quinonas/análisis , Espectrofotometría/métodosRESUMEN
Bioavailability of rifampicin in 150 mg capsules manufactured by 5 different companies was studied. Conditions for investigation of the rate of the antibiotic transfer into solution with the use of the "Rotating Basket" apparatus were determined and statistically significant differences were found. The drugs also differed in the level and rate of antibiotic absorption into the blood of humans.
Asunto(s)
Rifampin/sangre , Absorción , Administración Oral , Adulto , Animales , Disponibilidad Biológica , Cápsulas , Humanos , Conejos , Rifampin/administración & dosificaciónRESUMEN
The properties of tetracycline hydrochloride tablets from various manufacturers were studied. Differences depending on the character of the coating were found: the film-coated tablets differed from dragee by a shorter period of the antibiotic transfer to solution, better disintegration, lower content of anhydroderivatives and higher stability. Correlation between the rate of tetracycline transfer to solution in vitro and the antibiotic absorption into blood on the oral use of the tablets was shown.
Asunto(s)
Tetraciclina/metabolismo , Disponibilidad Biológica , Cromatografía en Gel , Densitometría , Humanos , Técnicas In Vitro , Absorción Intestinal/efectos de los fármacos , Pronóstico , Solubilidad , Espectrofotometría , Comprimidos , Comprimidos Recubiertos , Tetraciclina/análisis , Factores de TiempoRESUMEN
Bioavailability of various ampicillin dosage forms was studied. No difference in the level and rate of the antibiotic absorption was observed with the use of ampicillin trihydrate and anhydrous ampicillin capsules and ampicillin trihydrate tablets. Significant differences in the rate of ampicillin transfer into solution from various dosage forms were noted in the studies with the "rotating basket" apparatus. No correlation between the rate of ampicillin transfer into solution and the level of ampicillin absorption was found.
Asunto(s)
Ampicilina/metabolismo , Administración Oral , Adulto , Ampicilina/administración & dosificación , Ampicilina/sangre , Disponibilidad Biológica , Cápsulas , Evaluación de Medicamentos , Humanos , Absorción Intestinal/efectos de los fármacos , Solubilidad , ComprimidosRESUMEN
Bioavailability of experimental tablets and capsules of oxacillin was studied. Significant differences in absorption of the antibiotic from the above dosage forms were found. By the amount of the antibiotic absorbed the capsules were 3 times more effective than the tablets containing the same amount of oxacillin. The therapeutic concentrations of oxacillin in the blood after the use of the capsules persisted by an hour longer than after the use of the tablets. The results of the study on oxacillin absorption in rabbits allowed a prediction of the antibiotic absorption levels in humans.
Asunto(s)
Oxacilina/sangre , Absorción , Administración Oral , Adulto , Animales , Disponibilidad Biológica , Cápsulas , Estudios de Evaluación como Asunto , Humanos , Conejos , Comprimidos , Equivalencia Terapéutica , Factores de TiempoRESUMEN
Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.
Asunto(s)
Tetraciclina/sangre , Adolescente , Adulto , Animales , Disponibilidad Biológica , Cápsulas , Ensayos Clínicos como Asunto , Evaluación de Medicamentos , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Tamaño de la Partícula , Excipientes Farmacéuticos/farmacología , Polvos , Conejos , Factores de TiempoRESUMEN
The content of admixtures in tetracycline stored under different conditions was determined with chromatographic and spectrophotometric methods. Biological activity, toxicity and colour of the drugs was tested. The changes in teh colour of tetracycline most pronounced on its storage at a temperature of 37 degrees C and elevated humidity were not accompanied by an increase in the content of anhydrotetracyclines. In parallel with the changes in the colour of tetracycline, the loss of its biological activity up to 30 per cent and increased toxicity were registered. The LD50 decreased by 40 per cent as compared to the initial level. Simultaneously an additional spot with high chromatographic mobility (Rf 0.98--1.0) was detected on thin-layer chromatograms. It was shown that the processes of tetracycline degradation resulting in marked darkening of the drug colour were not accompanied by an increase in the content of anhydro admixtures. They were probably the result of accumulation of other products which are as highly toxic and low active as the anhydroderivatives of tetracycline.
Asunto(s)
Contaminación de Medicamentos , Tetraciclina/aislamiento & purificación , Animales , Almacenaje de Medicamentos , Dosificación Letal Mediana , Ratones , Polvos , Comprimidos , Temperatura , Tetraciclina/análisis , Tetraciclina/toxicidad , Factores de TiempoRESUMEN
The rate of tetracycline hydrochloride transfer into solution from capsules containing different auxiliary substances was studied. It was shown that the dispersity level of tetracycline hydrochloride powder had no significant effect on the capsule disintegration and the rate of the antibiotic transfer into solution. The effect of the auxiliary substance composition on the capsule disintegration and the rate of the antibiotic dissolution was shown. The rate of tetracycline liberation from the capsules containing tetracycline hydrochloride without additives or the antibiotic in combination with 23 per cent of lactose was 4 to 6 times higher than that from the capsules with magnesium carbonate or calcium phosphate as the auxiliary substances.
Asunto(s)
Excipientes Farmacéuticos/farmacología , Tetraciclina/farmacología , Disponibilidad Biológica , Cápsulas , Cinética , Polvos , Solubilidad , Tetraciclina/análisisRESUMEN
Chromatographic purity of erythromycin base preparations manufactured in the USSR with various technological procedures and those of 4 foreign firms was studied. All the preparations studied in addition to the main component of erythromycin A contained 5 to 7 per cent of erythromycin C and about 1.5 to 3.5 per cent of a non-identified component possessing a somewhat lower chromatographic mobility than erythromycin C. The admixture of 0.5--1 per cent of anhydroerythmycin was found in many erythromycin preparations. The preparations of some foreign firms contained also a number of additional substances. It was shown that the antimicrobial activity of anhydroerythromycin was 50-60 times lower than that of erythromycin. Direct correla;ion between the level of the antimicrobial activity of the market prepaetions of erythromycin and the level of its chemical purity was noted.
Asunto(s)
Eritromicina/análisis , Animales , Cromatografía en Capa Delgada , Eritromicina/análogos & derivados , Eritromicina/toxicidad , RatonesAsunto(s)
Antibacterianos/metabolismo , Absorción , Administración Oral , Animales , Antibacterianos/administración & dosificación , Disponibilidad Biológica , Sangre/efectos de los fármacos , Cápsulas , Cloranfenicol/metabolismo , Ensayos Clínicos como Asunto , Cristalografía , Griseofulvina/metabolismo , Humanos , Técnicas In Vitro , Absorción Intestinal/efectos de los fármacos , Penicilinas/metabolismo , Excipientes Farmacéuticos/farmacología , Proyectos de Investigación , Solubilidad , Relación Estructura-Actividad , Comprimidos , Tetraciclinas/metabolismo , Equivalencia Terapéutica , Factores de TiempoRESUMEN
Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found.
Asunto(s)
Disponibilidad Biológica , Biofarmacia , Tetraciclina/administración & dosificación , Administración Oral , Animales , Cobayas , Humanos , Absorción Intestinal , Cinética , Conejos , Comprimidos , Comprimidos Recubiertos , Tetraciclina/sangre , Factores de TiempoRESUMEN
The results and conditions of separation and quantitative determination of the admixtures of epi- and anhydro-derivatives of tetracycline in its market products were compared and analyzed using the following chromatographic methods: chromatography in a thin layer of a sorbent in 2 modifications, circular paper chromatography, chromatography on a column of gel Sephadex G-25. The comparison of the results of the study provided recommendation of the column chromatography with gel Sephadex G-25 for separate or summation quantitative determination of 4-epitetracycline. The method of chromatography in a thin layer of a sorbent may be successfully used for semiquantitative determination of the admixture levels in tetracycline market drugs.
Asunto(s)
Tetraciclina/análisis , Cromatografía en Gel/métodos , Cromatografía en Papel/métodos , Cromatografía en Capa Delgada/métodos , Densitometría , Contaminación de Medicamentos , Tetraciclinas/análisisRESUMEN
Alfa- and delta forms of cephalosporin were compared. Biological activity, lantimicrobial spectrum and innocuousness of the forms and their physico-chemical properties were investigated with the methods of infrared and ultraviolet spectrophotometry and derivatography. No significant differences in the biological properties of alfa- and delta forms of cephalosporin were found. However, the ingrared spectrum of the delta-form was indicative of higher stability of its molecule, which was confirmed by higher thermostability of delta-cephalosporin.