Abstract:
PURPOSE:To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. METHODS:Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler. RESULTS:For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1 μm. CONCLUSIONS:The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Longest PW,Son YJ,Holbrook L,Hindle Mdoi
10.1007/s11095-013-1001-zsubject
Has Abstractpub_date
2013-06-01 00:00:00pages
1608-27issue
6eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract::A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018929531410
更新日期:1993-04-01 00:00:00
abstract::Unsymmetrical aryl(heteroaryl)methyl isopropyl ester analogues of nifedipine, in which the 2-nitrophenyl group at C-4 is replaced by a 2- or 3-pyridyl substituent, were synthesized and evaluated as calcium-channel antagonists using guinea pig ileal longitudinal smooth muscle. The point of attachment of the C-4 pyridyl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015941706008
更新日期:1990-09-01 00:00:00
abstract:PURPOSE:[corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorptio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020412817716
更新日期:2002-10-01 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:To investigate the effect of γ-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)₃/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens. METHODS:Microspheres were irradiated with ⁶⁰Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tet...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1019-2
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011902625609
更新日期:1999-04-01 00:00:00
abstract::Micelle-associated epoetin is still a possible explanation for the upsurge of pure red blood cell aplasia associated with subcutaneous use of epoetin alpha in patients with chronic renal failure. ...
journal_title:Pharmaceutical research
pub_type: 评论,信件
doi:10.1007/s11095-006-9573-5
更新日期:2006-03-01 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
doi:10.1007/s11095-005-5276-6
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model. METHODS:400 ug of CNDs is injected intravenously to mice bearing melanoma cell line...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0784-7
更新日期:2012-09-01 00:00:00
abstract::Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. H...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018940122382
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. MET...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1887-3
更新日期:2016-06-01 00:00:00
abstract::The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. beta-Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018974131236
更新日期:1993-12-01 00:00:00
abstract:PURPOSE:Overexpression of the serine protease urokinase (uPA) is recognised as an important biomarker of metastatic disease and a druggable anticancer target. Plasminogen activator inhibitor type-2 (PAI-2/SerpinB2) is a specific uPA inhibitor with proven potential for use in targeted therapy. However, PAI-2 is rapidly ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1517-x
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:This study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2720-6
更新日期:2019-12-17 00:00:00
abstract:PURPOSE:Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1936-y
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy po...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1010904815275
更新日期:2001-07-01 00:00:00
abstract:PURPOSE:To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture. METHODS:Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9331-3
更新日期:2008-04-01 00:00:00
abstract::Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-019-2689-1
更新日期:2020-01-03 00:00:00
abstract:PURPOSE:The aim of this study was to investigate whether biodegradable nanocapsules could be obtained by the emulsification-diffusion technique. METHODS:This technique consists of emulsifying an organic solution containing an oil, a polymer, and a drug in an aqueous solution of a stabilizing agent. The subsequent addi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011934328471
更新日期:1998-07-01 00:00:00
abstract:PURPOSE:The objective of this investigation was to determine, using the Caco-2 cell culture model, the extent to which the paracellular and transcellular routes contributed to the transport of passively absorbed drugs. An effort was also made to determine the controlling factors in this process. METHODS:We selected a ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012111008617
更新日期:1997-09-01 00:00:00
abstract:PURPOSE:To identify High Molecular Weight Products (HMWP) formed in human insulin formulation during storage. METHODS:Commercial formulation of human insulin was stored at 37°C for 1 year and HMWP was isolated using preparative size exclusion chromatography (SEC) and reverse phase (RP) chromatography. The primary stru...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1600-3
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:To show, using a model study, how electronic structure theory can be applied in combination with LC/UV/MS/MS for the prediction and identification of oxidative degradants. METHODS:The benzyloxazole 1, was used to represent an active pharmaceutical ingredient for oxidative forced degradation studies. Bond disso...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000041469.96466.12
更新日期:2004-09-01 00:00:00
abstract::Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of n...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016247206531
更新日期:1995-05-01 00:00:00
abstract:PURPOSE:To study the expression of P-glycoprotein (P-gp), lung resistance-related protein (LRP), and caveolin-1 (cav-1) in the human bronchial epithelial cell line 16HBE14o-. METHODS:The presence of P-gp, LRP, and cav-1 in 16HBE14o- cell layers was evaluated using immunocytochemical staining and visualization with con...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023230328687
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1324-4
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To study the pulmonary absorption and tolerability of various formulations of the decapeptide cetrorelix acetate in rats by a new aerosol delivery system (ASTA-ADS) for intratracheal application. METHODS:Using the ASTA-ADS, cetrorelix liquid formulations (aqueous solutions for ultrasonic nebulization) were fir...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011028227155
更新日期:2001-06-01 00:00:00
abstract::A quantitative analysis of the dependence of dissolution rate on the relative surface area occupied by two non-interacting drug mixtures from co-compressed slabs is described. The results from the experimental dissolution rates of each component from naproxen/phenytoin co-compressed slabs under laminar flow conditions...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018979419714
更新日期:1994-10-01 00:00:00
abstract:PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016028707130
更新日期:1996-08-01 00:00:00
abstract:PURPOSE:Recent studies have demonstrated the potential for a triglyceride (TG) mimetic prodrug to promote the delivery of mycophenolic acid (MPA) to the lymphatic system. Here, the metabolic pathways that facilitate the lymphatic transport of the TG prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) were exam...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1579-9
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:The present investigation describes a formulative study for the development of innovative drug delivery systems for bromocriptine. METHODS:Solid lipid nanoparticles (SLN) based on different lipidic components have been produced and characterized. Morphology and dimensional distribution have been investigated b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9514-y
更新日期:2008-07-01 00:00:00