Abstract：
PURPOSE:Hydrogen/deuterium (H/D) exchange over a range of temperatures suggests a protein structural/mobility transition in the solid state below the system glass transition temperature (Tg). The purpose of this study was to determine whether solid-state protein stability correlates with the difference between storage temperature and apparent Td where an abrupt change in mobility occurs, or alternatively, the extent of H/D exchange at a single temperature correlates directly to protein stability in lyophilized solids. METHODS:Solid-state H/D exchange was monitored by FTIR spectroscopy to study the extent of exchange and the apparent transition temperature in both pure recombinant human serum albumin (rHSA) and rHSA formulated with sucrose or trehalose. H/D exchange of freeze-dried formulations at 11% RH and temperatures from 30 to 80°C was monitored. Protein stability against aggregation at 40°C/11% RH for 6 months was assessed by size exclusion chromatography (SEC). RESULTS:Both sucrose and trehalose showed equivalent protection of protein secondary structure by FTIR. The rHSA:sucrose formulation showed superior long-term stability at 40°C by SEC over the trehalose formulation, but the apparent Td determined from H/D exchange was much higher in the trehalose formulation. Instead, the extent of H/D exchange (X∞) was lower in the sucrose formulation at the temperature of the stability studies (40°C) than found for the trehalose formulation, which was consistent with better stability in the sucrose formulation. CONCLUSIONS:While apparent Td did not correlate with protein stability for rHSA, the extent of H/D exchange, X∞, did.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Fang R,Obeidat W,Pikal MJ,Bogner RHdoi
10.1007/s11095-020-02897-7subject
Has Abstractpub_date
2020-08-13 00:00:00pages
168issue
9eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-020-02897-7journal_volume
37pub_type
杂志文章abstract：:The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018993610801
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:Our previous studies indicated that drug leaked from discoidal reconstituted high density lipoprotein (d-rHDL) during the remodeling behaviors induced by lecithin cholesterol acyl transferase (LCAT) abundant in circulation, thus decreasing the drug amount delivered into the target. In this study, arachidonic ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1273-3
更新日期：2014-07-01 00:00:00
abstract：PURPOSE:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9573-8
更新日期：2008-07-01 00:00:00
abstract：PURPOSE:To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2'-Azobis(-amidinopropane) dihydrochloride (AAPH). METHODS:AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solut...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-1199-x
更新日期：2005-02-01 00:00:00
abstract：PURPOSE:The purpose of this study was to evaluate the feasibility of delivering vapreotide, a somatostatin analogue, by transdermal iontophoresis. METHODS:In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying vapreotide transport into and across ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2005-08-01 00:00:00
abstract：:Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016380104424
更新日期：1984-05-01 00:00:00
abstract：PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
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更新日期：2003-04-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2018-02-21 00:00:00
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更新日期：2002-04-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2003-05-01 00:00:00
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更新日期：2020-02-19 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2010-10-01 00:00:00
abstract：PURPOSE:Within-subject dependency of observations has a strong impact on the evaluation of population pharmacokinetic (PK) and/or pharmacodynamic (PD) models. To our knowledge, none of the current model evaluation tools correctly address this issue. We present a new method with a global test and easy diagnostic plot wh...
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更新日期：2011-08-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2003-11-01 00:00:00
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更新日期：2012-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2013-07-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1997-12-01 00:00:00
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更新日期：1999-05-01 00:00:00
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pub_type： 杂志文章,已发布勘误
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更新日期：2018-07-25 00:00:00
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更新日期：2015-01-01 00:00:00
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更新日期：2014-07-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1995-09-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2002-05-01 00:00:00
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更新日期：1997-01-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1987-04-01 00:00:00
abstract：:The relationship between pKa and skin irritation in man is studied for a homologous series of benzoic acid derivatives, which permeate through human skin at comparable rates (15-88 micrograms/cm2/hr). Skin irritation and pKa are correlated for pKa less than or equal to 4. Laser Doppler velocimetric assessment of skin ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015931105660
更新日期：1988-10-01 00:00:00
abstract：:Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
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更新日期：2018-09-05 00:00:00
abstract：:The interaction between several marker solutes and a polyolefin laminate polymer was studied in several solutions. Solutions studied included mixtures of sodium chloride and dextrose (at concentrations more less typical of i.v. administration solutions) and several actual i.v. products [lactated Ringer's injection, Di...
journal_title：Pharmaceutical research
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更新日期：1991-06-01 00:00:00
