Spectroscopic Analysis of Highly Concentrated Suspensions of Bovine Somatotropin in Sesame Oil

Low Viscosity Highly Concentrated Injectable Nonaqueous Suspensions of Lysozyme Microparticles

“…It is challenging to prevent denaturation and aggregation of peptides and proteins at high concentrations, whether in solution or suspension form. ,− Oxidation due to the oil has been visible for Factor IX in soybean oil, whereas miglyol oil has been used as the solvent to suspend a bovine growth hormone releasing factor analogue for 10 weeks with no reported loss in stability measured by reverse-phase HPLC and FTIR. , In addition, at high concentrations (up to 300 mg/mL), the stability of bovine somatotropin in sesame oil was confirmed by fluorescence, Raman, and FTIR spectroscopy . In benzyl benzoate, insulin, protein C, and a proprietary monoclonal antibody are stable in sustained release polymer formulations. − …”

“…Additional characterization of the stability of lysoyzme was not performed, since lysozyme is very stable. Thus, lysozyme would not be a good indicator of the stability of more fragile proteins, with regard to both denaturation and the formation of irreversible protein soluble and insoluble aggregates. ,,− However, the moisture content in the suspension was examined, as it is an important factor that influences protein stability. The moisture controls protein hydration in the solid state, which is known to have a large effect on protein stability.…”

Stability of Protein Pharmaceuticals: An Update

“…While our understanding of protein solubility is still imperfect, there have been significant advances in the past 20 years (326,328). Salted-out proteins still retain activity and native-like structure (327,(329)(330)(331), and the precipitation is fully reversible upon dilution.…”

Formulation Design and High-Throughput Excipient Selection Based on Structural Integrity and Conformational Stability of Dilute and Highly Concentrated IgG1 Monoclonal Antibody Solutions

“…8 The destabilization is probably because of the increased intermolecular contacts in the concentrated state and may be generally characteristic of proteins under such conditions. 9,10 It should be emphasized, however, that these conclusions were based on studies with only two mAbs whose behavior, in fact, differed significantly from one another. In this work, we have therefore examined the conformational stability of a third IgG1 mAb at high concentrations and then asked the additional question of whether excipient molecules that conformationally stabilize an mAb at low protein concentrations have similar effects in more concentrated mAb solutions.…”

“…The biophysical methods employed in this study are subtle variations of spectroscopic and calorimetric techniques originally modified for use in highly scattering solutions and the rational for their use to monitor the conformational stability of proteins is described elsewhere. [10][11][12][13] To better address some of the challenges associated with formulation and stabilization of highly concentrated antibody formulations, we performed a systematic analysis of the physical structure and conformational thermal stability of a humanized IgG1 mAb at 1 and 100 mg/mL as a function of solution temperature (10 • C-87.5 • C) and pH (3)(4)(5)(6)(7)(8). An empirical phase diagram (EPD)-based approach was utilized to compare significant trends in the complex biophysical data sets obtained for the mAb at low and high concentrations.…”