PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-6 (6)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
Year of Publication
Document Types
1.  Effect of Processing Parameters on the Physical Stability of Silicone Coatings 
AAPS PharmSciTech  2012;13(4):1116-1119.
doi:10.1208/s12249-012-9843-y
PMCID: PMC3513466  PMID: 22936408
prefilled syringes; protein aggregation; quartz crystal microbalance; silicone leaching
2.  The effect of neighboring amino acid residues and solution environment on the oxidative stability of tyrosine in small peptides 
AAPS PharmSciTech  2007;8(4):176-183.
The effects of neighboring residues and formulation variables on tyrosine oxidation were investigated in model dipeptides (glysyl tyrosine, N-acetyl tyrosine, glutamyl tyrosine, and tyrosyl arginine) and tripeptide (lysyl tyrosyl lysine). The tyrosyl peptides were oxidized by light under alkaline conditions by a zero-order reaction. The rate of the photoreaction was dependent on tyrosyl pKa, which was perturbed by the presence of neighboring charged amino acid residues. The strength of light exposure, oxygen headspace, and the presence of cationic surfactant, cetyltrimethylammonia chloride had a significant effect on the kinetics of tyrosyl photooxidation. Tyrosine and model tyrosyl peptides were also oxidized by hydrogen peroxide/metal ions at neutral pH. Metal-catalyzed oxidation followed first-order kinetics. Adjacent negatively charged amino acids accelerated tyrosine oxidation owing to affinity of the negative charges to metalions, whereas positively charged amino acid residues disfavored the reaction. The oxidation of tyrosine in peptides was greatly affected by the presence of adjacent charged residues, and the extent of the effect depended on the solution environment.
doi:10.1208/pt0804102
PMCID: PMC2750688
Tyrosine; oxidation; kinetics; charge-effect; ionic strength; antioxidants
3.  Removal of peroxides in polyethylene glycols by vacuum drying: Implications in the stability of biotech and pharmaceutical formulations 
AAPS PharmSciTech  2006;7(3):E47-E53.
The purpose of this study was to investigate the utility of vacuum drying for removing peroxides from polyethylene glycols (PEGs). PEG solutions (PEG 1450 and PEG 20000) containing varying levels of peroxides were prepared by storing under different light and temperature conditions. PEGs containing low and high levels of peroxides were vacuum dried from dilute and concentrated solutions (2.5%, 7.5%, 15%, and 50% wt/vol of PEG 1450 and 2.5%, 7.5%, 15%, and 25% wt/vol of PEG 20000). Ferrous ion oxidation in presence of ferric ion indicator xylenol orange (FOX) colorimetric assay was used to determine the concentration of peroxides. Peroxide content in PEGs increased upon storage. The increase was more pronounced when PEGs were stored at higher temperatures and exposed to light. Vacuum drying at 0.1 mm Hg for 48 hours at 25°C resulted in greater than 90% decrease in the level of peroxides in all cases except when high peroxide containing 25% wt/vol solution of PEG 20000 or 50% wt/vol solution of PEG 1450 were dried. The reduction in the level of peroxides for PEGs dried from high peroxide containing 25% wt/vol solution of PEG 2000 and 50% wt/vol solution of PEG 1450 was found to be 88% and 52%, respectively. Oxidation of methionine in Met-Leu-Phe peptide was significantly reduced when vacuum-dried PEGs were used. Vacuum drying PEG solutions at low pressures is an effective method for the removal of the residual peroxides present in commercially available PEGs.
doi:10.1208/pt070362
PMCID: PMC2750504  PMID: 16796364
Freeze drying; peroxides; polyethylene glycol; proteins; vacuum drying
4.  Measurement of fluid viscosity at microliter volumes using quartz impedance analysis 
AAPS PharmSciTech  2005;5(3):68-81.
The purpose of this work was to measure viscosity of fluids at low microliter volumes by means of quartz crystal impedance analysis. To achieve this, a novel setup was designed that allowed for measurement of viscosity at volumes of 8 to 10 μL. The technique was based on the principle of electromechanical coupling of piezoelectric quartz crystals. The arrangement was simple with measurement times ranging from 2 to 3 minutes. The crystal setup assembly did not impose any unwanted initial stress on the unloaded quartz crystal. Quartz crystals of 5- and 10-MHz fundamental frequency were calibrated with glycerol-water mixtures of known density and viscosity prior to viscosity measurements. True frequency shifts, for the purpose of this work, were determined followed by viscosity measurement of aqueous solutions of sucrose, urea, PEG-400, glucose, and ethylene glycol at 25°C±0.5°C. The measured viscosities were found to be reproducible and consistent with the values reported in the literature. Minor inconsistencies in the measured resistance and frequency shifts did not affect the results significantly, and were found to be experimental in origin rather than due to electrode surface roughness. Besides, as expected for a viscoelastic fluid, PEG 8000 solutions, the calculated viscosities were found to be less than the reported values due to frequency dependence of storage and loss modulus components of complex viscosity. From the results, it can be concluded that the present setup can provide accurate assessment of viscosity of Newtonian fluids and also shows potential for analyzing non-Newtonian fluids at low microliter volumes.
doi:10.1208/pt050347
PMCID: PMC2750269  PMID: 15760080
viscosity; quartz crystal; impedance analysis; Newtonian fluids; viscoelastic fluids
5.  Effect of vacuum drying on protein-mannitol interactions: The physical state of mannitol and protein structure in the dried state 
AAPS PharmSciTech  2004;5(1):58-69.
The purpose of the present studies was to systematically investigate protein-mannitol interactions using vacuum drying, to obtain a better understanding of the effect of protein/mannitol wt/wt ratios on the physical state of mannitol and protein secondary structure in the dried state. Solutions containing β-lactoglobulin (βLg):mannitol (1∶1–1∶15 wt/wt) were vacuum dried at 5°C under 3000 mTorr of pressure. The physical state of mannitol was studied using x-ray powder physical state of mannitol was studied using x-ray powder diffractometry (XRPD), polarized light microscopy (PLM), Fourier-transform infrared (FTIR) spectroscopy, and modulated differential scanning calorimetry (MDSC). XRPD studies indicated that mannitol remained amorphous up to 1∶5 wt/wt βLg:mannitol ratio, whereas PLM showed the presence of crystals of mannitol in all dried samples except for the 1∶1 wt/wt βLg:mannitol dried sample. FITR studies indicated that a small proportion of crystalline mannitol was present along with the amorphous mannitol in dried samples at lower (less than 1∶5 wt/wt) βLg:mannitol ratios. The Tg of the dried 1∶1 wt/wt βLg:mannitol sample was observed at 33.4°C in MDSC studies, which indicated that at least a part of mannitol co-existed with protein in a single amorphous phase. Evaluation of the crystallization exotherms indicated that irrespective of the βLg:protein wt/wt ratio in the initial sample, the protein to amorphous mannitol ratio was below 1∶1 wt/wt in all dried samples. Second-derivative FTTR studies on dried βLg and recombinant human interferon α-2a samples showed that mannitol affected protein secondary structure to a varying degree depending on the overall mannitol content in the dried sample and the type of protein.
doi:10.1208/pt050110
PMCID: PMC2784861  PMID: 15198531
mannitol; proteins; vacuum drying; amorphous; protein structure
6.  Polyethylene glycol-induced precipitation of interferon alpha-2a followed by vacuum drying: Development of a novel process for obtaining a dry, stable powder 
AAPS PharmSci  2004;6(1):31-44.
Feasibility studies were performed on the development of a novel process based on polyethylene glycol (PEG)-induced precipitation of proteins followed by vacuum drying in the presence of sugars to obtain dry protein powders. Apparent solubility of interferon alpha-2a (IFNα2a) was determined in the presence of various PEGs and the effect of solution pH, ionic strength, and temperature was investigated. IFNα2a precipitate was dried at a shelf temperature of 25°C at 100 mTorr either as it is or in the presence of mannitol and/or trehalose. The dried IFNα2a formulations were subjected to accelerated stability studies at 40°C (3 months), and the stability was compared with that of a similar lyophilized formulation. The results indicated that more than 90% of the protein could be precipitated using 10% wt/vol PEG the protein could be precipitated using 10% wt/vol PEG 1450 at pH 6.5 at a solution ionic strength of 71 mM. Vacuum drying of the precipitate only resulted in the formation of insoluble aggregates of IFNα2a; however, this was prevented by the addition of either mannitol or trehalose. The addition of excess mannitol resulted in low residual moisture content and better handling of the final dried product. Accelerated storage stability did not show any aggregation and showed less than 5% formation of oxidized IFNα2a in the dried formulation containing IFNα2a: trehalose: mannitol in a 1∶10∶100 wt/wt ratio upon storage at 40°C for 3 months. The stability of this vacuum dried formulation was comparable with that of a similar lyophilized formulation.
doi:10.1208/ps060104
PMCID: PMC2750939  PMID: 18465256
protein formulation; polyethylene glycol (PEG); precipitation; vacuum drying; protein powders

Results 1-6 (6)