RESUMEN
Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation.
Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Budesonida/uso terapéutico , Cloro/toxicidad , Diterpenos/uso terapéutico , Descubrimiento de Drogas/métodos , Exposición por Inhalación/efectos adversos , Fenantrenos/uso terapéutico , Rolipram/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Animales , Budesonida/administración & dosificación , Budesonida/sangre , Química Farmacéutica , Diterpenos/administración & dosificación , Diterpenos/sangre , Portadores de Fármacos/química , Liberación de Fármacos , Compuestos Epoxi/administración & dosificación , Compuestos Epoxi/sangre , Compuestos Epoxi/uso terapéutico , Inyecciones Intramusculares , Masculino , Ratones Endogámicos , Microscopía Electrónica de Rastreo , Fenantrenos/administración & dosificación , Fenantrenos/sangre , Rolipram/administración & dosificación , Rolipram/sangre , Propiedades de SuperficieRESUMEN
Despite the importance of microsphere size for controlled drug delivery, little work has been done to quantitatively predict the distribution of microspheres from manufacturing techniques. This work presents a quantitative study that describes the size distribution of poly(lactide-co-glycolide) (PLG) microspheres. A fluid mechanics based correlation for the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow under non-coalescing conditions. The correlation was constructed and validated with experimentally obtained mean microsphere diameters prepared at different stirring speeds. In addition, a Rosin Rammler distribution function was found to give an accurate representation of the microsphere distribution. The spread of the microsphere size distribution was found to decrease with stirring speed. With the validation of the mathematical correlation, it is now possible to have a good estimate of the average microsphere size prior to microsphere preparation. This is directly relevant to the pharmaceutical industry where microspheres of specified mean diameter and size distribution are desirable.
