Spray-dried alginate microparticles for potential intranasal delivery of ropinirole hydrochloride: development, characterization and histopathological evaluation.

Ropinirole hydrochloride (RH) is an anti-Parkinson drug with relativity low oral bioavailability owing to its extensive hepatic first pass metabolism. Spray-dried mucoadhesive alginate microspheres of RH were developed and characterized followed by histopathological evaluation using nasal tissue isolated from sheep. Spherical microparticles having high product yield (around 70%) were obtained when the inlet temperature of spray drying was 140 °C. Fourier Transform Infrared (FTIR) studies revealed the compatibility of the drug with the polymer, and scanning electron microscopy (SEM) showed that drug-loaded microparticles were spherical, and the apparent surface roughness was inversely related to the ratio of polymer to drug. Furthermore, size of the spray-dried particles were in the range of 2.5-4.37 µm, depending on formulation. All formulations had high drug encapsulation efficiencies (101-106%). Drug loaded into the polymeric particles was in the amorphous state and drug molecules were molecularly dispersed in the polymeric matrix of the microparticles which were revealed by X-ray diffraction and differential scanning calorimetry (DSC), respectively. The in vitro drug release was influenced by polymer concentration. Histopathological study demonstrated that RH-loaded sodium alginate microparticles was safe to nasal epithelium. In conclusion, spray drying of RH using sodium alginate polymer has produced microparticles of suitable characteristics for potential intranasal administration.

Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler.

Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated 'worm-like' structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent.