Graziela Mezzalira

Development of Nanocapsule Suspensions and Nanocapsule Spray-Dried Powders Containing Melatonin

Suspensoes de nanocapsulas contendo melatonina foram preparadas pelo metodo de deposicao interfacial e caracterizadas (tamanho, morfologia e eficiencia de encapsulacao). Foram avaliadas as influencias do tipo de polimero, de oleo e de tensoativo sobre as caracteristicas dos produtos. A eficiencia de encapsulacao da melatonina variou de 30% a 56% e a natureza do polimero foi o parâmetro de maior influencia. De acordo com a maior eficiencia de encapsulacao, nanocapsulas preparadas com Eudragit S100 ® foram selecionadas para secagem por aspersao, objetivando-se aumentar a estabilidade fisica das suspensoes e controlar a liberacao da melatonina. O po obtido apresentou eficiencia de encapsulacao de 93% e nao sofreu nenhuma alteracao morfologica apos 12 meses de armazenamento. Este sistema apresentou perfil de liberacao controlado, comparativamente ao farmaco puro, o qual foi ajustado ao modelo monoexponencial. O mecanismo de liberacao da melatonina foi baseado em intumescimento e dissolucao do polimero.

Determining the simultaneous presence of drug nanocrystals in drug-loaded polymeric nanocapsule aqueous suspensions: A relation between light scattering and drug content

The encapsulation of lipophilic drugs in polymeric nanoparticles can form simultaneously both polymeric nanoparticles and drug nanocrystals. The objective was to detect the presence of nanocrystals in the nanoparticle suspensions using a simple methodology, and to determine if the nanocrystals are formed during preparation or by drug leakage from the particles during storage. Indomethacin was chosen as drug model. Unloaded and drug-loaded (1mg/mL) nanocapsules showed diameters close to 280nm and polydispersity lower than 0.20, remaining constant after 120 days. Comparing indomethacin loaded (3mg/mL) and unloaded formulations, variations in the scattered light depolarization degree indicated the simultaneous presence of nanocrystals and nanocapsules in the suspensions. A relation between the scattered light intensities and the drug precipitation was established. As a function of time, when the decrease in the Rayleigh ratios occurred, the drug contents decreased due to precipitation. On the other hand, when the Rayleigh ratios slightly increase, the drug contents are constant. The nanocrystals formed in the oversaturated formulations, agglomerate and precipitate during storage. When the drug is adsorbed on the nanocapsules, but the system is not oversaturated, no nanocrystal was formed and the formulation is physico-chemically stable at least for 150 days of storage.

Structural model of polymeric nanospheres containing indomethacin ethyl ester and in vivo antiedematogenic activity

The aim of this work was to establish a structural model for describing the organisation, at a molecular level, of nanospheres prepared by nanoprecipitation using poly(e-caprolactone), sorbitan monostearate and polysorbate 80. Therefore, different techniques were employed to characterise the systems such as dynamic and static light scattering, small angle X-ray scattering and release profile evaluations. The indomethacin ethyl ester that is insoluble in water and presents in vitro anti-inflammatory activity was encapsulated in the nanospheres. Furthermore, the antiedematogenic activity has been studied in rats. The unloaded and loaded nanosphere suspensions presented particle diameters of 186 nm and 208 nm, polydispersity lower than 0.2, ζ-potentials of ?40.7 mV and ?45.3 mV and pH 5.0 and 5.2, respectively. The depolarisation ratio showed constant values that were lower than 0.015 indicating that nanospheres in suspensions are isotropic, then being considered spherically shaped. SAXS analyses showed a partial organisation of the sorbitan monostearate and no peak relative to the crystallinity of the polymer, suggesting that this surfactant is retained in the polymer matrix of nanospheres. The structural organisation, at a molecular level, of those nanospheres corresponds to particles in which aggregates of sorbitan monostearate are stabilised by the polymeric chains. Additionally, the indomethacin ethyl ester-loaded nanospheres presented antiedematogenic activity after oral administration in rats, indicating that even though the ester is insoluble in gastric or intestinal media, those nanospheres were able to deliver it for a pharmacological response.