Solid Lipid Budesonide Microparticles for Controlled Release Inhalation Therapy

Abstract

Abstract. A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crystallinity, thermal properties, aerosol performance, and dissolution/diffusion release. The microparticle system was also compared to conventional spray-dried crystalline and amorphous budesonide samples. The particle size distributions of the crystalline, amorphous, and solid lipid microparticles, measured by laser diffraction, were similar; however, the microparticle morphology was more irregular than the spray-dried drug samples. The thermal response of the solid lipid microparticles suggested polymorphic transition and melting of the lipid, glycerol behenate (at~48°C and 72°C). No budesonide melting or crystallisation peaks were observed, suggesting that the budesonide was integrated into the matrix. X-ray powder diffraction patterns of the crystalline and amorphous budesonide were consistent with previous studies while the solid lipid microparticles showed two peaks, at approximately 21.3 and 23.5 2θ suggesting the metastable sub-α and primarily β′ form. Analysis of the in vitro diffusion/dissolution of the formulations was studied using a flow through model and curves analysed using difference/similarity factors and fitted using the Higuchi model. Regression analysis of this data set indicated differences in the t 0.5 , where values of 49.7, 35.3, and 136.9 min were observed for crystalline, amorphous, and the solid lipid microparticles, respectively. The aerosol performance (<5 μm), measured by multistage liquid impinger, was 29.5%, 27.3%, and 21.1±0.6% for the crystalline, amorphous, and the solid lipid microparticles, respectively. This study has shown that solid lipid microparticles may provide a useful approach to controlled release respiratory therapy.

Solid lipid microparticles as an approach to drug delivery

“…Sonication of the sample using an ultrasonic probe leads to a reduction of the particle size to few microns (Figure 2), suitable for specific administration routes such as pulmonary delivery [11,14,43].…”

“…However, it must be emphasise that substances in the micrometre range may exhibit biological properties that are different from their larger counterparts, although the major concerns about particle toxicity are associated with nanoscale materials [2]. Additional advantages of lipid particles include: increased bioavailability of sparingly water-soluble substances [4,7], modified release of incorporated drug, the possibility of avoiding the use of organic solvents for their preparation, relatively low production cost, feasibility of large-scale production and adequate physicochemical stability [1,3,10,11]. Moreover, their solid matrix protects encapsulated labile substances against degradation [8,12,13].…”

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

“…The endothermic peak of budesonide in the DSC curves was observed at 262°C, whereas no budesonide peaks were found in the NPs, indicating that budesonide was present in the molecularly dispersed state and well encapsulated in NPs. 24 …”

Preliminary Studies on Solid Lipid Microparticles of Loratadine for the Treatment of Allergic Reactions via the Nasal Route

“…Furthermore, systemic side effects of drugs reported via oral administration can be minimized/eliminated with controlled drug delivery by nasal administration of microparticles [5]. Microparticular carrier systems of LRT may also be used for efficient controlled release inhalation therapy in allergic respiratory reactions [6,7]. Hot surfactant solution at the same temperature was added to the mixture using the Ultra-Turrax T25 homogenizer.…”