Abstract：
:Adequate protein solubility is an important prerequisite for development, manufacture, and administration of biotherapeutic drug candidates, especially for high-concentration protein formulations. A previously established method for determining the relative apparent solubility (thermodynamic activity) of proteins using polyethylene glycol (PEG) precipitation is adapted for screening and comparing monoclonal antibody (mAb) candidates where only limited quantities (≤1 mg) are available. This micro-PEG assay is used to evaluate various broadly neutralizing mAb candidates to HIV-1 viral spike (gp120 and gp41 glycoproteins). Using ∼1 mg of VRC01-WT mAb per assay, the precision of the micro-PEG assay was established. A series of 7 different broadly neutralizing mAbs to the HIV-1 viral spike proteins were compared by curve shape (%PEG vs. protein concentration), %PEGmidpoint determinations, and extrapolated apparent solubility values. Numerous formulation conditions were then evaluated for their relative effects on the VRC01-WT mAb. The PEGmidpt and apparent solubility values of VRC01-WT mAb decreased as the solution pH increased and increased as NaCl and arginine were added. A final optimization of the micro-PEG assay established that amounts as low as 0.1-0.2 mg can be used. Thus, the micro-PEG assay has significant potential as a relative solubility screening tool during candidate selection and early formulation development.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Toprani VM,Joshi SB,Kueltzo LA,Schwartz RM,Middaugh CR,Volkin DBdoi
10.1016/j.xphs.2016.05.021subject
Has Abstractpub_date
2016-08-01 00:00:00pages
2319-27issue
8eissn
0022-3549issn
1520-6017pii
S0022-3549(16)41457-7journal_volume
105pub_type
杂志文章abstract：:An on-line, high-performance frontal analysis (HPFA)-high-performance liquid chromatographic system was developed for the enantioselective determination of a low level of unbound ketoprofen (KP) that is in equilibrium with KP that is bound to protein. The system consists of three subsystems (HPFA system, preconcentrat...
journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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abstract：:A reinvestigation of the constituents of the Osage orange (maclura pomifera) yielded, in addition to the previously reported triterpenses (lupeol, butyrospermol, and lupan-3beta,20-diol), the pigments osajin and pomiferin, and a previously unreported constituent. The structure of this new compound was investigated. On...
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doi：10.1002/jps.2600640121
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600700631
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abstract：:6-Amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid proved to be a potent hypolipidemic agent in rodents at the low dose of 20 mg/kg/d. The agent effectively reduced the liver enzyme activities required for the synthesis of triglycerides and cholesterol. Lower lipid levels in tissue were observed in mice but not i...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600740713
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.23723
更新日期：2013-11-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20642
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abstract：:In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism a...
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doi：10.1002/jps.2600661115
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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abstract：:A rapid solubility-screening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug developmen...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.21041
更新日期：2008-04-01 00:00:00
