RESUMO
Recently, owing to their pharmaceutical and clinical utility, mini-tablets have been well studied by researchers. Mini-tablets are usually manufactured by compression molding using a multiple-tip tool in a rotary tableting machine. Owing to their special structure, ensuring uniformity is a very important challenge in the manufacturability of mini-tablets using the multiple-tip tool. In this study, we aimed to evaluate the weight variation in mini-tablets produced by a multiple-tip tool, which is considered to be the root cause affecting the uniformity, and to investigate the physical properties of drug granules and tableting conditions in a rotary tableting machine that could reduce this weight variation. In addition, the relationship between these factors and response was visualized using response surface analysis. It was shown that the weight variation in mini-tablets produced by a multiple-tip tool was reduced when using a forced feeder compared with an open feeder. Furthermore, in the case of an open feeder, the optimal range of the average particle size diameter of drug granules and the rotational speed of the rotating disc in the rotary tableting machine were determined from response surface analysis. It was suggested that it is possible to reduce the weight variation in the mini-tablets by selecting drug granules with an average particle size diameter of 100-150 µm and using tableting conditions with a rotational speed of 40-60 rpm. This study elucidated the factors that affect uniformity and determined their optimal range for the manufacture of mini-tablets.
Assuntos
Excipientes/química , Comprimidos/química , Celulose/análogos & derivados , Celulose/química , Composição de Medicamentos , Lactose/química , Manitol/química , Tamanho da Partícula , Pressão , Amido/química , Ácidos Esteáricos/química , Propriedades de SuperfícieRESUMO
The aim of this study was to investigate two types of chitosan-modified poly (DL-lactic-co-glycolic acid) (PLGA) nanocomposite particles containing salmon calcitonin for pulmonary delivery, which were obtained using spray drying fluidized bed granulation (Agglomaster™) and dry powder coating techniques (Mechanofusion™), respectively. The physicochemical properties, pulmonary distribution, pulmonary clearance rate as well as in vivo hypocalcemia actions of the two types of nanocomposite particles were investigated. As indicated by scanning electron micrographs, soft matrix nanocomposite particles and soft ordered nanocomposite particles were produced by Agglomaster™ and Mechanofusion™, respectively. Both forms of chitosan-modified PLGA nanocomposite particles exhibited a high inhalation efficiency, i.e. more than 50% of the two types of nanocomposite particles could be deposited in the deep lung of male Wistar rats. However, the chitosan-modified PLGA nanocomposite particles designed by Agglomaster™ exhibited superior properties to those obtained by Mechanofusion™ with respect to the redispersibility of fine particles in aqueous liquid, the pulmonary retention time and pharmacological effects. In addition, compared with non-modified PLGA nanocomposite particles, the chitosan-modified PLGA nanocomposite particles obtained by Agglomaster™ exhibited enhanced pulmonary absorption of salmon calcitonin via the lung. The findings in this study suggest that the spray drying fluidized bed granulation technique is superior to the dry powder coating technique for producing chitosan-modified dry powder formulations containing salmon calcitonin for inhalation. This can be attributed to the avoidance of aggregation of chitosan-modified PLGA nanocomposite particles when using Agglomaster™ rather than Mechanofusion™.
Assuntos
Quitosana/administração & dosagem , Quitosana/química , Ácido Láctico/química , Nanocompostos/administração & dosagem , Nanocompostos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Ácido Poliglicólico/química , Absorção , Administração por Inalação , Animais , Calcitonina/administração & dosagem , Calcitonina/química , Química Farmacêutica/métodos , Hipocalcemia/tratamento farmacológico , Pulmão/efeitos dos fármacos , Masculino , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pós/administração & dosagem , Pós/química , Pós/farmacologia , Ratos , Ratos Wistar , Tecnologia Farmacêutica/métodosRESUMO
Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion(TM) technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.