Flocculated amorphous itraconazole nanoparticles for enhanced in vitro supersaturation and in vivo bioavailability.

Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit(®) L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH.

Low viscosity highly concentrated injectable nonaqueous suspensions of lysozyme microparticles.

Subcutaneous injection of concentrated protein and peptide solutions, in the range of 100-400 mg/mL, is often not possible with a 25- to 27-gauge needle, as the viscosity can be well above 50 cP. Apparent viscosities below this limit are reported for suspensions of milled lysozyme microparticles up to nearly 400 mg/mL in benzyl benzoate or benzyl benzoate mixtures with safflower oils through a syringe with a 25- to 27-gauge needle at room temperature. These apparent viscosities were confirmed using a cone-and-plate rheometer.

Formation of stable submicron protein particles by thin film freezing.

Purpose: Highly stable, submicron lactate dehydrogenase (LDH) and lysozyme particles may be produced by thin film freezing (TFF) of aqueous solutions followed by lyophilization.

Methods: The LDH activity was determined by measuring the decrease in absorbance of NADH over time for the reaction of pyruvate to lactate. For lysozyme the particle morphology was determined by scanning electron microscopy (SEM) and compared with the specific surface area (BET) and the particle size, as measured by laser light scattering,

Results: Protein particles with an average diameter of 300 nm and 100% enzyme activity upon reconstitution (for LDH) were formed by TFF.