RESUMO
In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D50) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 µm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 µg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 µg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies.
Assuntos
Cafeína/análise , Cafeína/síntese química , Química Farmacêutica/métodos , Cristalização/métodos , Dapsona/síntese química , Administração por Inalação , Varredura Diferencial de Calorimetria/métodos , Linhagem Celular , Dapsona/análise , Dessecação/métodos , Composição de Medicamentos/métodos , Inaladores de Pó Seco , Humanos , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Termogravimetria/métodos , Difração de Raios X/métodosRESUMO
A hanseníase é uma doença endêmica no Brasil e constitui grave problema de saúde pública. Em números absolutos, o Brasil é o segundo país que mais registra novos casos da doença por ano no mundo. O tratamento da hanseníase compreende: quimioterapia específica, supressão dos surtos reacionais, prevenção de incapacidades físicas, reabilitação física e psicossocial. A síndrome sulfona é uma condição multissistêmica potencialmente grave que pode ocorrer durante o tratamento de algumas dermatoses, entre elas a hanseníase. Relatamos um caso de síndrome de hipersensibilidade à dapsona (SHD) em um paciente masculino, de 32 anos, ocorrida durante o tratamento de hanseníase multibacilar...
Assuntos
Humanos , Masculino , Adulto , Dapsona/análise , Dapsona/farmacologia , Dapsona/síntese química , Dapsona , Hanseníase Multibacilar , Sulfonas/análise , Sulfonas/classificação , Sulfonas/imunologiaRESUMO
Com o objetivo de se obter, atraves do metodo da latenciacao, pro-farmacos de acao antimalarica prolongada e menor toxicidade, foram sintetizados derivados acriloilicos da dapsona e das seguintes sulfas antimalaricas: sulfadiazina, sulfadimetoxina, sulfadoxina, sulfametoxazol, sulfametoxidiazina, sulfametoxipiridazina, sulfamonometoxina e sulfisoxazol. Os compostos assim obtidos foram submetidos as analises classicas, espectrofotometricas e de ressonancia magnetica protonica
Assuntos
Antimaláricos/metabolismo , Dapsona/metabolismo , Malária/etiologia , Sulfonamidas/metabolismo , Antimaláricos/síntese química , Brasil , Química , Dapsona/síntese química , Tempo de Reação , Espectrofotometria , Análise Espectral , Sulfonamidas/síntese químicaRESUMO
Some aspects of the sulfone action on the murine leprosy were studied in rats, which were inoculated by the intraperitoneal route with 5, 5 mg of M. lepraemurium and then treated with 4- 4'-diamino-diphenylsulfone (DDS). The treatment was made by the oral route, 0,2 or 0,3 per cent of DDS being added to the food. The animals were divided into the following lots: Lot 1A - 20 rats treated with 0,2 per cent of DDS. Lote 1B - 20 untreated control rats. 2A - 20 rats inoculated with bacilli obtained from an animal of the lot 1A, preliminarily treated with DDS during 180 days; these animals then received 0,2 per cent of DDS mixed with the food. Lot 2B - 20 untreated control rats, which were inoculated with bacilli recovered from a rat of the lot 1B. Lot 3A - 20 rats inoculated with bacilli recovered from an animal of the lot 2A, which had previously been treated with DDS for 180 days; afterwards these animals received 0,2 per cent of DDS in the food. Lot 3B - 20 rats inoculated with the same material as the lot 3A, but afterwards treated with 0,3 per cent of DDS given with the food. Lot 3C - 20 rats inoculated with same material as the lot 3A, and kept as untreated controls. Lot 3D - 20 rats inoculated with bacilli obtained from an animal of the lot 2B; these rats were afterwards treated with DDS (0,3 per cent in the food). Lot 3E - 20 untreated control rats, inoculated with the same material as the lot 3D. The results of the treatment were based upon the survical time and the intensity of the lesions. The statistical analysis of the medium survical time in these lots of animals shows, that they constitute 3 groups. The lots which integrate these groups do not present significant difference when compared together. A first group comprises the control animals (lots 1B, 2B and 3E); a second group includes the animals inoculated with bacilli recovered from the control rats and then treated with DDS (lots 1A and 3D) and the animals inoculated with bacilli obtained from previo