Abstract：
PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro by utilization of a modified Ussing chamber diffusion cell apparatus and in vivo by single-pass intestinal perfusion. RESULTS:Carbon dioxide (CO2) bubbling directly onto rabbit ileum epithelium induced an increase in drug permeability. Mechanistic studies indicated that effects due to CO2 bubble evolution, such as increased drug dissolution rates, mucus thinning/stripping, and pH buffer effects did not contribute to increases in drug flux. Cellular enzyme (5'-ND and LDH) and total protein release assays did not indicate cell membrane perturbation and/or damage. CO2 bubbling induced a reduction in transepithelial electrical resistance (TEER) indicating epithelial disruption due to a structural change of the paracellular pathway. This was further substantiated by a MW dependence on paracellular marker flux. In addition, tissue recovery was relatively rapid, approximately 20 min. CONCLUSIONS:CO2 bubbling directly onto the intestinal epithelium induced enhanced drug permeability due to an alteration of the paracellular pathway. This, in addition to fluid flow and membrane hydrophobicity concepts, may account for observed increases in drug flux.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Eichman JD,Robinson JRdoi
10.1023/a:1011936901638subject
Has Abstractpub_date
1998-06-01 00:00:00pages
925-30issue
6eissn
0724-8741issn
1573-904Xjournal_volume
15pub_type
杂志文章abstract：OBJECTIVE:Amorphous pharmaceuticals, a viable approach to enhancing bioavailability, must be stable against crystallization. An amorphous drug can be stabilized by dispersing it in a polymer matrix. To implement this approach, it is desirable to know the drug's solubility in the chosen polymer, which defines the maxima...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9784-z
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:Performance of a transdermal delivery system (TDS) can be affected by exposure to elevated temperature, which can lead to unintended safety issues. This study investigated TDS and skin temperatures and their relationship in vivo, characterized the effective thermal resistance of skin, and identified the in vitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2171-x
更新日期：2017-07-01 00:00:00
abstract：PURPOSE:To improve upon the theory of reasoned action and apply it to pharmaceutical research, we investigated the effects of relevant appraisals attributes, and past behavior of physicians on the use of drug information sources. We also examined the moderating effects of practice characteristics. METHODS:A mail quest...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012143915886
更新日期：1997-10-01 00:00:00
abstract：:The pharmacokinetics of methylergometrine were investigated in the rat, with emphasis on the role of biliary excretion and enterohepatic recirculation in the overall disposition of the drug. A linked-rat model, where the bile from a rat receiving a constant rate of iv infusion of methylergometrine was allowed to flow ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015871122537
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (Mphi). METHODS:Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamin...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022271020390
更新日期：2003-02-01 00:00:00
abstract：PURPOSE:To study the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for recombinant tuberculosis (TB) antigen, TB10.4-Ag85B, with the ultimate goal of pulmonary delivery as vaccine for the prevention of TB. MATERIALS AND METHODS:Recombinant TB antigens were purified from E. co...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0028-7
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:To evaluate 26 marketed oncology drugs for time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential to generate reactive intermediates. Assess clinical drug-drug interaction (DDI) risk using static mechanistic models. METHODS:Human liver microsomes and CYP-spe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0724-6
更新日期：2012-07-01 00:00:00
abstract：PURPOSE:To study the miscibility of proteins and polymer excipients in frozen solutions and freeze-dried solids as protein formulation models. METHODS:Thermal profiles of frozen solutions and freeze-dried solids containing various proteins (lysozyme, ovalbumin, BSA), nonionic polymers (Ficoll, polyvinylpyrrolidone [PV...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026412107574
更新日期：2000-10-01 00:00:00
abstract：PURPOSE:The purpose of this study was to establish a useful methodology, possibly providing information on the stoichiometry of pharmaceutical drug salts obtained from salt screening by using a multiwell plate and a Raman microscope. METHODS:Tamoxifen salt screening was conducted with monobasic and polybasic acids on ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9644-7
更新日期：2006-04-01 00:00:00
abstract：:Previous work from this laboratory showed site-dependent variations in the apparent permeability of insulin as measured using the everted rat gut sac technique, with the greatest permeability in the distal jejunum and the lowest in the duodenum (5). To quantify better the rate and extent of insulin absorption from the...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015894125611
更新日期：1992-08-01 00:00:00
abstract：PURPOSE:We examined the subcellular distribution of the basic drugs, chlorpromazine (CPZ), imipramine (IMP) and biperiden (BP), in rat liver, and evaluated the contribution of lysosome (Lys) to their intracellular distribution in comparison with that of mitochondria (Mit). METHODS:In an in vivo distribution, the conce...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016061330387
更新日期：1996-06-01 00:00:00
abstract：PURPOSE:The lack of effective delivery vehicles impedes in vivo applications of siRNA. The trimethyl chitosan-cysteine (TC) nanoparticles (NPs) were developed for in vivo delivery of tumor necrosis factor α (TNF-α) siRNA via oral gavage and intraperitoneal injection. METHODS:The nanoparticles formulated from TC conjug...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1086-4
更新日期：2013-10-01 00:00:00
abstract：PURPOSE:It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. METHODS:The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023803706746
更新日期：2003-06-01 00:00:00
abstract：PURPOSE:Polyesters with hydrophilic domains, i.e., poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(L-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1685-3
更新日期：2015-09-01 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：:Cholinesterases are ubiquitous carboxylesterase type B enzymes capable of hydrolyzing the neurotransmitter acetylcholine which are transiently expressed in multiple germline, embryonic, and tumor cells. The acute poisoning effects of various organophosphorous compounds are generally attributed to their irreversible co...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015867021628
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS:The ASES technique using high pressure carbon dioxide modified with e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000008053.69903.c1
更新日期：2003-12-01 00:00:00
abstract：PURPOSE:To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer. METHODS:Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine-nicotinamide (CBZ-NCT) cocr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2622-7
更新日期：2019-04-23 00:00:00
abstract：PURPOSE:To develop a semi-physiological-based model describing simultaneously the time course of immature and mature B-lymphocytes after topotecan (TPT) administration to tumor-bearing rats. METHODS:Twenty-four tumor-bearing BDIX male rats received a single 6 mg/kg intra-peritoneal dose of TPT or saline. Mature and im...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0025-x
更新日期：2010-03-01 00:00:00
abstract：PURPOSE:To develop a non-viral gene delivery system in the form of an oil-in-water (o/w) lipid emulsion. METHOD:Cationic lipid emulsions were formulated with soybean oil, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a cationic emulsifier and other co-emulsifiers. The physical characteristics of the l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007553106681
更新日期：2000-03-01 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:In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products. METHODS:Different sugars as ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1634-1
更新日期：2015-07-01 00:00:00
abstract：PURPOSE:Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. METHODS:We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, inclu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016034913181
更新日期：1996-02-01 00:00:00
abstract：PURPOSE:Orthorhombic crystals of paracetamol exhibit good technological properties during compression. The purpose of this study was to investigate the compression behavior of this substance and to compare it to that of monoclinic paracetamol. From the crystal structure, it could be hypothesized that sliding planes are...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011954800246
更新日期：1998-07-01 00:00:00
abstract：PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9595-2
更新日期：2008-09-01 00:00:00
abstract：:Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015982204926
更新日期：1989-08-01 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:Magnetic resonance imaging (MRI) is widely used for diagnostic imaging in preclinical studies and in clinical settings. Considering the intrinsic low sensitivity and poor specificity of standard MRI contrast agents, the enhanced delivery of MRI tracers into tumors is an important challenge to be addressed. This...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1736-9
更新日期：2015-11-01 00:00:00
abstract：UNLABELLED:PURPOSE; The aim of this study was to investigate asparagine (Asn) deamidation and aspartate (Asp) isomerization and to measure the content of isoaspartate (isoAsp) in recombinant human interleukin-11 (rhIL-11). METHODS:The rhIL-11 control and heat stressed samples were characterized with trypsin and endopr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1019814713428
更新日期：2002-08-01 00:00:00
abstract：:The internalization of a neuromodulatory adrenocorticotropic hormone (ACTH) analogue, [125I]ebiratide (H-Met(O2)-Glu[125I]His-Phe-D-Lys-Phe-NH(CH2)2NH2), was examined in cultured monolayers of bovine brain capillary endothelial cells (BCEC). HPLC analysis of the incubation solution showed that [125I]ebiratide was not ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015848531603
更新日期：1992-04-01 00:00:00
