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 solution model, the drugs and AAPH were dissolved in a mixture of acetonitrile and aqueous buffer and incubated at elevated temperatures to evaluate oxidative degradation. The effects of pH and drug-AAPH ratio on the kinetics of the reaction were evaluated for compound A. Commonly used antioxidants were also evaluated by addition to solutions of drug and AAPH. In the solid-state model, blends of drug with microcrystalline cellulose were treated with AAPH and placed at elevated temperature and humidity to evaluate solid state oxidation. RESULTS:Use of AAPH resulted in selective oxidation of the model drugs by a free radical initiated process. The scope of the technique was further investigated in detail using compound A. The rate of oxidation of compound A varied directly with the concentration of AAPH. The pseudo first-order rate constants for the oxidative degradation were calculated from the kinetic data. The antioxidants were rank-ordered based on their quenching activity on the rates of AAPH initiated oxidation for compound A. The concept was extended to oxidation in solid state. CONCLUSIONS:The proposed AAPH model is useful in assessing oxidative stability of drug candidates in development.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Betigeri S,Thakur A,Raghavan Kdoi
10.1007/s11095-004-1199-xsubject
Has Abstractpub_date
2005-02-01 00:00:00pages
310-7issue
2eissn
0724-8741issn
1573-904Xjournal_volume
22pub_type
杂志文章abstract:PURPOSE:To evaluate the influence of the main biopharmaceutical factors on the viability of a new probiotic yeast strain, using dynamic in vitro systems simulating human gastric/small intestinal (TIM) and large intestinal (ARCOL) environments. METHODS:The viability of Saccharomyces cerevisiae CNCM I-3856 throughout th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0620-5
更新日期:2012-06-01 00:00:00
abstract::Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N'-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coating for colon-specific drug delivery. The gastrointestinal absorption of theophylline from cap...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016283027139
更新日期:1995-02-01 00:00:00
abstract:PURPOSE:To explain thermal stability enhancement of an organic compound, sucralose, with cyclodextrin based metal organic frameworks. METHODS:Micron and nanometer sized basic CD-MOFs were successfully synthesized by a modified vapor diffusion method and further neutralized with glacial acetic acid. Sucralose was loade...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-2059-1
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:Polyethylenimine (PEI) is a highly effective gene delivery vector, but because it is an off-the shelf material, its properties may not be optimal. To investigate the effects of the protonation properties of the polymer, we generated PEI derivatives by acetylating varying fractions of the primary and secondary a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000016251.42392.1e
更新日期:2004-02-01 00:00:00
abstract::A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015896121377
更新日期:1991-02-01 00:00:00
abstract:PURPOSE:The aim of this study is to investigate the effects of 50% ethyl acetate extracts of grapefruit juice (GFJ) and orange juice (OJ) on the transport activity of P-glycoprotein (P-gp) in the rat small intestine. METHODS:The efflux of P-gp substrates from rat everted sac in the absence or presence of verapamil, GF...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016100715125
更新日期:2002-06-01 00:00:00
abstract:PURPOSE:Several phenomena in tablets indicate that an inhomogeneous pore distribution is formed during the compaction process. Examples are lamination and the capping of corners. In order to gain an understanding of the relation between structure and compact properties, analyzing the structure in a location dependent m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-5280-x
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS:Protein powders were characterized using particle size analysis, thermogravimetric an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018828425184
更新日期:1999-02-01 00:00:00
abstract::Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015872617511
更新日期:1990-02-01 00:00:00
abstract:PURPOSE:To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS:We have developed a new approach to the sequence a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012070726480
更新日期:1997-04-01 00:00:00
abstract:PURPOSE:The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetramethylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. METHODS:The study was carried out by investigati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016055517724
更新日期:1996-02-01 00:00:00
abstract:PURPOSE:The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS:Mathematical modeling, applied to transdermal d...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016216611809
更新日期:1995-12-01 00:00:00
abstract:PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020354809581
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:To develop a new bionic system from an existing drug dissolution/absorption simulating system (DDASS) to simultaneously predict the release and absorption of enteric-coated formulations. METHODS:In accordance with the pH-dependent characteristics of enteric-coated formulations, the modified DDASS was designed ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0905-3
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:A theoretical study was performed to generate a pharmacophore model for chemically diverse structures that specifically interact with the diltiazem binding site of L-type calcium channels. METHODS:Via molecular mechanics and quantum chemical methods solvation energies, logP values, conformational and electroni...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015037800903
更新日期:1999-10-01 00:00:00
abstract:PURPOSE:The current study aimed to examine the pharmaceutical applications of the focused-ion-beam (FIB) in the inhalation aerosol field, particularly to particle porosity determination (i.e. percentage of particles having a porous interior). MATERIALS AND METHODS:The interior of various spray dried particles (bovine ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9276-6
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. METHODS:Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2453-y
更新日期:2018-07-03 00:00:00
abstract::Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018904825958
更新日期:1993-03-01 00:00:00
abstract:PURPOSE:The addition of high amounts of calcium remains a pharmaceutical concern due to its precipitation with phosphate in total parenteral nutrient (TPN) admixtures, compromising also the stability of the lipid emulsion. MATERIALS AND METHODS:Calcium-phosphate solubility was compared when using binary PN solutions v...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9671-7
更新日期:2008-11-01 00:00:00
abstract:PURPOSE:A patient was denoted to be generic brittle (GB) if they had a negative opinion about generics (e.g. prior history of a switch problem) or took the innovator brand of their most problematic anti-epileptic drug (AED) when generic was available. The aim of this hypothesis-generating study was to assess possible g...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-2781-6
更新日期:2020-02-26 00:00:00
abstract:PURPOSE:We have shown that the three human prostate xenograft tumors, i.e. the androgen-dependent CWR22 tumor, and the androgen-resistant CWR22R and CWR91 tumors, are comparable to patient tumors in their expression of prostate specific antigen, multidrug resistance p-glycoprotein, p53 and Bcl-2 and in their sensitivit...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011921031564
更新日期:1998-11-01 00:00:00
abstract:PURPOSE:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9365-6
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability. METHODS:99mTc-...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2548-5
更新日期:2018-11-29 00:00:00
abstract:PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9568-2
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:To develop a semi-distributed liver model for the evaluation of saturable sinusoidal uptake and binding kinetics of the Oatp1a4 substrate digoxin. METHODS:In the perfused rat liver, two successive digoxin doses of 42 and 125 microg were administered, and the outflow concentration was determined by LC/MS/MS. [1...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0204-9
更新日期:2010-09-01 00:00:00
abstract:PURPOSE:Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models. METHODS:We characterize...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9989-9
更新日期:2009-12-01 00:00:00
abstract:PURPOSE:The long-term stability and nasal absorption characteristics of a basic nasal formulation of azetirelin, a thyrotropin-releasing hormone analog and its absorption enhancement by incorporation of acylcarnitines in the formulation were investigated. METHODS:The long-term stability of basic nasal azetirelin formu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011952804479
更新日期:1998-01-01 00:00:00
abstract::Pediatric brain tumors are most common cancers in childhood and among the leading causes of death in children. Chemotherapy has been used as adjuvant (i.e. after) or neoadjuvant (i.e. before) therapy to surgery and radiotherapy for the management of pediatric brain tumors for more than four decades and gained more att...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-013-1196-z
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine wh...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-8383-5
更新日期:2005-12-01 00:00:00
abstract::The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tend...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016292232513
更新日期:1995-03-01 00:00:00