RESUMEN
Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.
Asunto(s)
Resinas Acrílicas/química , Antiinflamatorios no Esteroideos/administración & dosificación , Preparaciones de Acción Retardada/química , Diclofenaco/administración & dosificación , Administración Oral , Antiinflamatorios no Esteroideos/química , Niño , Diclofenaco/química , Humanos , Tamaño de la Partícula , Solubilidad , Suspensiones/químicaRESUMEN
In this study, recombinant human interleukin-2 (rhIL-2) containing poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared for pulmonary administration by modified w/o/w double emulsion solvent extraction method and the effects of various formulation parameters on the physicochemical properties of the microparticles were investigated. Microparticles in suitable size for pulmonary administration (4.02 µm) were obtained by increasing dichloromethane volume used in the organic phase. Also, a very high encapsulation efficiency (99.22%) value could be reached in these microparticles. In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, rhIL-2 extracted from microparticles having a similar band with native rhIL-2 showed that the protein was not affected by the encapsulation process. The release curves of microparticles exhibited a biphasic fashion, characterized by a fast release phase at initial 1 day, followed by a slower one on the remaining days. Bioactivity investigations using T cells show that rhIL-2 encapsulated in PLGA microparticles retain their biological activity.
Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Interleucina-2/administración & dosificación , Ácido Láctico/química , Pulmón/metabolismo , Ácido Poliglicólico/química , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Composición de Medicamentos , Humanos , Interleucina-2/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Estabilidad Proteica , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Linfocitos T/efectos de los fármacosRESUMEN
The objective of this work was to develop and evaluate reconstitutable suspensions of ibuprofen-loaded microspheres prepared with an acrylic polymer (Eudragit RS-PM). The microspheres were prepared by the quasi-emulsion solvent diffusion technique. To prepare reconstitutable suspension formulation, the microspheres used had a mean particle size of 316.6 microm and 99.8% loading efficiency. Xanthan gum was chosen as the suspending agent for the suspension formulations. D-sorbitol was used to impart palatability of suspensions. The amount of D-sorbitol affected sedimentation volume and redispersibility properties of suspensions. The highest improving effect was shown with 20.0% and 25.0% of D-sorbitol concentrations. It was observed that dispersion media of suspensions showed non-Newtonian flow characteristics. To ensure minimum drug leakage from the microspheres into the suspension, the pH was buffered at 3.60 using citrate buffer. The ibuprofen content calculated from the suspended microspheres was consistent with that from microspheres alone. This result indicated that no leakage of drug occurred from the microspheres in the suspension on storage. Moreover, the same release rate of ibuprofen from the microspheres suspension and microspheres alone indicated that the suspension medium studied did not affect the property of drug release. This study suggested that stable suspensions of ibuprofen-loaded microspheres could be formulated with 0.6% w/v xanthan gum by the addition of 20% w/v D-sorbitol.
Asunto(s)
Resinas Acrílicas/química , Antiinflamatorios no Esteroideos/química , Portadores de Fármacos , Ibuprofeno/química , Tampones (Química) , Química Farmacéutica , Composición de Medicamentos , Concentración de Iones de Hidrógeno , Cinética , Microesferas , Tamaño de la Partícula , Polisacáridos Bacterianos/química , Reología , Solubilidad , Sorbitol/química , Suspensiones , Gusto , Tecnología Farmacéutica/métodosRESUMEN
OBJECTIVE: The aim of this study was the preparation and evaluation of dry powder formulations of recombinant human interleukin-2 (rhIL-2)-loaded microparticles to be administered to the lung by inhalation. METHODS: As indicated in our previous study, the microparticles were prepared by modified water-in-oil-in-water (w(1)/o/w(3)) double emulsion solvent extraction method using poly(lactic-co-glycolic acid) (PLGA) polymers. The dry powder formulations were prepared with blending of microparticles and mannitol as a coarse carrier. The actual aerodynamic characteristics of the microparticles alone and prepared mixtures with mannitol are evaluated by using the eight-stage Andersen cascade impactor. RESULTS: Due to the low tapped density of microparticles (<0.4 g/cm(3)), the theoretical aerodynamic diameter (MMADt) values were calculated (<5 µm) on the basis of the geometrical particle diameter and tapped density values. The lowest tapped density value (0.17 g/cm(3)) belongs to the cyclodextrin-containing formulation. According to the results obtained using the cascade impactor, the emitted doses for all microparticle formulations were found to be rather high and during the aerosolization for all the formulations except F3 and F5, >90% of the capsule content was determined to be released. However, the actual aerodynamic diameter (MMADa) values were seen to be higher than the MMADt values. The blending of the microparticles with mannitol allowed their aerodynamic diameters to decrease and their fine particle fraction values to increase. CONCLUSION: The obtained results have shown that the mixing of rhIL-2-loaded microparticles with mannitol possess suitable aerodynamic characteristics to be administered to the lungs by inhalation.
Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Inhaladores de Polvo Seco , Interleucina-2/química , Ácido Láctico/química , Ácido Poliglicólico/química , Administración por Inhalación , Diuréticos Osmóticos/química , Humanos , Manitol/química , Microscopía Electrónica de Rastreo/métodos , Microesferas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , PolvosRESUMEN
The aim of this study was to prepare and evaluate microspheres containing ibuprofen. Microspheres were prepared by modified quasi-emulsion solvent diffusion method. The influence of formulation factors (drug-polymer ratio, volumes of solvent, polyvinyl alcohol concentration and type of polymer) on the morphology, particle size distribution, drug loading capacity, micromeritical properties and the in vitro release characteristics of the microspheres were investigated. Physical characterizations of ibuprofen microspheres were also carried out using scanning electron microscopy, X-ray diffractometry and IR spectrophotometry. It was found that the yield of preparation was dependent on the initial temperature gradient between the emulsion phases. When there was an initial difference of temperature between the aqueous phase and dispersed emulsion phases, yield of preparation was increased distinctly. The drug loading capacities were very high for all formulations of the microspheres which were obtained. Mean particle size changed by changing the drug-polymer ratio, volumes of solvent or polyvinyl alcohol concentration. The flow properties were much improved over those of the original crystals. In vitro dissolution results showed that the release rate of ibuprofen was modified in all formulations. Although ibuprofen release rates from Eudragit RS microspheres were very slow, they were fast from Eudragit RL microspheres. These results observed that if Eudragit RS and Eudragit RL are used in combination, optimum release profiles may be obtained.