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Self-emulsifying lipids (SEL) were used as a stabilizer for the preparation of dexamethasone lipid nanoparticles by membrane emulsification employing Shirasu porous glass. The effect of process and formulation parameters on the size and polydispersity and dexamethasone solubility in lipids and its release from lipid nanoparticles were investigated. Lipid phase pressure (40–80 kPa), membrane pore-size (0.1 − 0.4 µm) and agitation speed (300 − 900 rpm) did not affect the size and polydispersity of SEL. However, the size was increased with increasing lipid content and fatty acid chain of the lipid. Sizes of < 250 nm were achieved from TEGO® care:Gelucire® blend and it increased to 487 nm by adding 20% w/w of hard fat. The highest solubility of dexamethasone was found in TEGO® care 450 (29 mg/g). Release from the lipid nano-dispersions was extended with no burst effect and the absolute release was increased with increasing lipid content. [ABSTRACT FROM AUTHOR]

The aim of this study was to prepare amorphous indomethacin nanoparticles in aqueous media and to determine in situ their increased saturation solubility and dissolution rate. Drug nanosuspensions with a Z-average of ∼300 nm were prepared by wet media milling and afterwards freeze-dried. The drug solid state was analyzed by DSC, XRD and FTIR before and after the milling process. Milling of amorphous indomethacin with polyvinylpyrrolidone (PVP) as stabilizer resulted in an amorphous nanosuspension which could not be redispersed in the nanosize range after freeze-drying. The combination of PVP and poloxamer 407 resulted in crystalline nanoparticles: poloxamer 407, a polymer with high molecular weight, competed with PVP for surface coverage, and hindered the interaction between PVP and indomethacin. This indicated the importance of sufficient drug-PVP interactions on the drug particle surface for amorphous state stabilization. Redispersable amorphous indomethacin nanoparticles were obtained by combining the anti-recrystallization effect of PVP with the particle size stabilization provided by sodium dodecyl sulfate. Solubility studies were performed in situ . The solubility of crystalline micronized indomethacin of 6.7 ± 1.3 µg/mL was increased up to 17.3 ± 2.8 µg/mL by its amorphization, with a factor of increase of 2.6. Indomethacin amorphization increased its dissolution rate by a factor of 30. Indomethacin nanocrystals resulted in an increased solubility of 2.6 times, with a solubility of 17.2 ± 0.4 µg/mL. The highest increase was obtained with amorphous indomethacin nanoparticles with a solubility of 35 ± 1.6 µg/mL and 5.2 times higher than the solubility of the original indomethacin. Amorphous indomethacin nanoparticles resulted in the highest dissolution rate, which increased from 0.003 µg/(mL s) to 2.328 µg/(mL s). The synergistic effect obtained by the combination of nanosize and amorphous solid state was demonstrated. [ABSTRACT FROM AUTHOR]