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. The intrinsic viscosity regressed from the Kreiger-Dougherty model was only slightly above the Einstein value of 2.5, indicating the increase in viscosity relative to that of the solvent was caused primarily by the excluded volume. Thus, the increases in viscosity from electrical double layer interactions (electroviscous effects), solvation of the particles, or deviations of the particle shape from a spherical geometry were minimal, and much smaller than typically observed for proteins dissolved in aqueous solutions. The small electroviscous effects are expected given the negligible zeta potential and thin double layers in the low dielectric constant organic solvent. The suspensions were resuspendable after a year, with essentially constant particle size after two months as measured by static light scattering. The lower apparent viscosities for highly concentrated protein suspensions relative to protein solutions, coupled with these favorable characteristics upon resuspension, may offer novel opportunities for subcutaneous injection of therapeutic proteins.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040681PMC
http://dx.doi.org/10.1021/la9023426DOI Listing

Publication Analysis

Top Keywords

apparent viscosities
12
highly concentrated
8
lysozyme microparticles
8
subcutaneous injection
8
concentrated protein
8
25- 27-gauge
8
27-gauge needle
8
benzyl benzoate
8
electroviscous effects
8
low viscosity
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!