RESUMO
People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.
Assuntos
Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Lidocaína/administração & dosagem , Miconazol/administração & dosagem , Nanopartículas/química , Polímeros/química , Antifúngicos/administração & dosagem , Antifúngicos/química , Varredura Diferencial de Calorimetria , Quitosana , Humanos , Lidocaína/química , Miconazol/química , Nanopartículas/administração & dosagem , Difração de Raios XRESUMO
Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.
Assuntos
Antifúngicos/química , Miconazol/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/química , Composição de Medicamentos , Miconazol/farmacologia , Polímeros/químicaRESUMO
Succinyl-ß-CD derivatives were obtained by green synthesis with degrees of substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain albendazole (ABZ):succinyl-ß-CD inclusion complexes. Phase solubility diagrams indicated that both succinyl-ß-CD derivatives formed 1:1 molar ratio ABZ complexes, but the complex with DS 2.9 has a lower formation constant. The presence of stable inclusion complexes in aqueous solution was confirmed by NMR. For both complexes the aromatic moiety is encapsulated into the host cavity. In the solid-state, 13C and 15N NMR spectral differences between ABZ and ABZ included in spray-dried systems showed that strong structural changes occurred in the systems. At least two different ABZ amorphous species were identified based on DS. ABZ species were stable over more than six months based on spectral data. Finally, the influence of DS in the number and type of the inclusion complexes was elucidated.
Assuntos
Albendazol/química , Ressonância Magnética Nuclear Biomolecular , beta-Ciclodextrinas/químicaRESUMO
Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.
Assuntos
Antifúngicos/administração & dosagem , Carragenina/administração & dosagem , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Miconazol/administração & dosagem , Adesividade , Administração Bucal , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Carragenina/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Miconazol/química , Resistência à TraçãoRESUMO
Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures.
Assuntos
Antifúngicos/química , Adesividade , Química Farmacêutica , Miconazol , Polímeros , Difração de Raios XRESUMO
Las buenas prácticas de fabricación (BPF) sistematizan un conjunto de recomendaciones cuya aplicación es, sin lugar a dudas el camino más eficaz para asegurar la calidad de los productos farmacéuticos. Su finalidad es doble: por un lado, proveer a la industria farmacéutica de una referencia para la evaluación y aplicación de procedimientos de fabricación adecuados, y por el otro, faciliar las tareas de fiscalización y control de las autoridades sanitarias, así como la armonización de las respectivas normativas nacionales. Las normas nacionales de BPF ofrecen un marco regulatorio para asegurar que las mezclas de nutrición parenteral extemporáneas preparadas sean adecuadas para el fin propuesto, garantizando que cumplan con los requisitos de calidad, seguridad, pureza y eficacia preestablecidos, así como también presentar evidencia documentada completa del cumplimiento de las buenas practicas de fabricación...
Assuntos
Humanos , Masculino , Feminino , Misturas Alimentícias , Normas de Qualidade de Alimentos , Nutrição ParenteralRESUMO
Las buenas prácticas de fabricación (BPF) sistematizan un conjunto de recomendaciones cuya aplicación es, sin lugar a dudas el camino más eficaz para asegurar la calidad de los productos farmacéuticos. Su finalidad es doble: por un lado, proveer a la industria farmacéutica de una referencia para la evaluación y aplicación de procedimientos de fabricación adecuados, y por el otro, faciliar las tareas de fiscalización y control de las autoridades sanitarias, así como la armonización de las respectivas normativas nacionales. Las normas nacionales de BPF ofrecen un marco regulatorio para asegurar que las mezclas de nutrición parenteral extemporáneas preparadas sean adecuadas para el fin propuesto, garantizando que cumplan con los requisitos de calidad, seguridad, pureza y eficacia preestablecidos, así como también presentar evidencia documentada completa del cumplimiento de las buenas practicas de fabricación...(AU)
Assuntos
Humanos , Masculino , Feminino , Normas de Qualidade de Alimentos , Misturas Alimentícias , Nutrição ParenteralRESUMO
Microspheres of Bacillus subtilis were prepared using sodium alginate. Some typical properties of microencapsulated systems, such as microorganism content, particle size, and germination time, were studied. Calcium alginate microspheres were obtained by the emulsification method, dripping into a solution of calcium salt. The conditions of the preparation steps were very soft to produce calcium alginate microspheres containing cells with no apparent changes in general biological properties. The hydrogel matrix provides protection without preventing communication with the surrounding medium.
Assuntos
Alginatos/química , Bacillus subtilis , Bacillus subtilis/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Composição de Medicamentos , Emulsões , Excipientes , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da PartículaRESUMO
O exame de um cäo de quatro meses de idade, macho, sem raça definida, com peso de 5,7kg mostrou que ele se apoiava com os cotovelos e apresentava desvio acentuado bilateral do rádio e da ulna. Ao exame radiográfico, observou-se fratura proximal bilateral do rádio. Após avaliaçöes clínica e radiológica foi indicada a osteotomia corretiva e distraçäo osteogênica do membro anterior esquerdo. O procedimento cirúrgico constou de osteotomia na diáfise proximal do rádio e ulna e emprego de fixadores externos compostos por quatro pinos de Kirschner e duas barras metálicas rosqueadas, configurando um fixador tipo II, bilateral uniplanar dinâmico. Antes da fixaçäo dos pinos com acrílico, os fragmentos ósseos fraturados foram separados em aproximadamente 0,5cm. Após 10 dias, iniciou-se a distraçäo de 1,0mm/dia durante 30 dias. A consolidaçäo da fratura foi observada radiograficamente aos 67 dias após a intervençäo, quando o aparelho foi removido. Procedimento semelhante foi realizado no membro anterior direito, quando o animal se encontrava com 16 meses de idade. Foi necessária a retirada de uma cunha óssea de aproximadamente 1,0cm para a correçäo angular. Atualmente, o cäo mostra apoio normal do membro anterior esquerdo e discreto desvio valgus do direito devido à quebra do implante
Assuntos
Animais , Masculino , Osso e Ossos , Anormalidades Congênitas , Cães , Osteogênese por DistraçãoRESUMO
The production of polymeric complexes in many active drugs with reticulated povidone increased dissolved component percentage. In this work made use a coevaporation technique. Complex formation has been tested by X Ray Diffractometry and Differential Scanning Calorimetry. The percentage of dissolution was determined to the USP XXIII Edition methodology. As can be seen from the results, the Atenolol-reticulated Povidone complexes has greater solubility than the Atenolol mixed with Lactose as excipient.