Abstract：
PURPOSE:Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenous to the lungs; and second, to compare the aerodynamic size and performance of the particles with theoretical estimates based on bulk powder measurements. METHODS:Dry powders were made of water-soluble excipients (e.g., lactose, albumin) combined with water-insoluble material (e.g., lung surfactant), using a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinhaler device in vitro in both an Andersen cascade impactor and an Aerosizer. RESULTS:By properly choosing excipient concentration and varying the spray drying parameters, a high degree of control was achieved over the physical properties of the dry powders. Mean geometric diameters ranged between 3 and 15 microm, and tap densities between 0.04 and 0.6 g/cm3. Theoretical estimates of mass mean aerodynamic diameter (MMAD) were rationalized and calculated in terms of geometric particle diameters and bulk tap densities. Experimental values of MMAD obtained from the Aerosizer most closely approximated the theoretical estimates, as compared to those obtained from the Andersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1-3 microm, exhibited emitted doses as high as 96% and respirable fractions ranging up to 49% or 92%, depending on measurement technique. CONCLUSIONS:Dry powders engineered as large and light particles, and prepared with combinations of GRAS (generally recognized as safe) excipients, may be broadly applicable to inhalation therapy.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Vanbever R,Mintzes JD,Wang J,Nice J,Chen D,Batycky R,Langer R,Edwards DAdoi
10.1023/a:1018910200420subject
Has Abstractpub_date
1999-11-01 00:00:00pages
1735-42issue
11eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章abstract：PURPOSE:To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates. METHODS:The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000016241.84630.06
更新日期：2004-02-01 00:00:00
abstract：PURPOSE:Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. MATERIALS AND METHODS:Diabetes was ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9256-x
更新日期：2007-07-01 00:00:00
abstract：PURPOSE:A theory and computer programs running on Microsoft Excel for Windows for calculation of solution pH, buffer formula, and buffer capacity at a given ionic strength and temperature were developed. The theory does not limit the category of buffer components, the number of buffer components, or the number of ioniz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012037819211
更新日期：1997-03-01 00:00:00
abstract：PURPOSE:We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. METHODS:Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. RESU...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016051600828
更新日期：1996-05-01 00:00:00
abstract：PURPOSE:Cell-based permeability screens are widely used to identify drug-P-glycoprotein (PGP) interaction in vitro. However, their reliability in predicting the impact of PGP on human drug pharmacokinetics is poorly defined. The aim was to determine whether a quantitative relationship exists between PGP-mediated altera...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000026434.82855.69
更新日期：2004-05-01 00:00:00
abstract：PURPOSE:To examine the iontophoretic delivery of ALA as a function of pH and to determine the principal mechanisms responsible for its electrotransport. METHODS:Anodal iontophoretic transport of ALA was measured as a function of its concentration and pH of the donor solution. Experiments were performed in vitro using ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011050829531
更新日期：2001-03-01 00:00:00
abstract：PURPOSE:Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016053729362
更新日期：1996-12-01 00:00:00
abstract：PURPOSE:To evaluate the use of an in vitro intestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. METHODS:In vivo peroral absorption and in vitro steady-state intestinal permeability coefficients were det...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012148300807
更新日期：1997-12-01 00:00:00
abstract：:Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016226601988
更新日期：1995-04-01 00:00:00
abstract：PURPOSE:The aim of this work was to develop PEGylated poly(alkylcyanoacrylate) nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymer. METHODS:PEGylated and non-PEGylated nanoparticles were formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles si...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011973625803
更新日期：1998-04-01 00:00:00
abstract：PURPOSE:Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma. METHODS:Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy reveal...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1604-z
更新日期：2015-06-01 00:00:00
abstract：PURPOSE:To investigate the properties of phenylboronic acid-functional poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their compatibility with COS-7 cells. METHODS:Copolymers of phenylboronic acid-functional poly(amid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1688-0
更新日期：2015-09-01 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：:The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp2-D-Phe5]GHRP, from erodible, non-cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated at pH 7.4 as a function of buffer concentration. Although the swell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018902404036
更新日期：1993-07-01 00:00:00
abstract：PURPOSE:Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9834-1
更新日期：2009-05-01 00:00:00
abstract：PURPOSE:To study Cereport (RMP-7, bradykinin B2 agonist) effects on human brain microvascular endothelial cell (HBMEC) monolayer permeability. METHODS:HBMEC grown on transwell membranes were exposed to Cereport. The monolayer permeability was determined with [14C]-inulin (MW. 5,200) and [3H]-dextran (MW. 70,000). RES...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018938722768
更新日期：1999-09-01 00:00:00
abstract：PURPOSE:The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. METHODS:In vivo activity was investigated using six volunteers by determining the reduction in colony form...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1016002322692
更新日期：1996-04-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9009-z
更新日期：2005-01-01 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
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1550-9
更新日期：2015-05-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1094-4
更新日期：2013-10-01 00:00:00
abstract：:The pharmacokinetic parameters of leuprolide acetate, a potent analogue of LH-RH, were determined in rats and dogs after i.v. and s.c. dosing with leuprolide solution. The effective human dose of once-a-month injectable microspheres of leuprolide was estimated to be about 3.2 to 8.1 mg analogue/month using these param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015818504906
更新日期：1991-06-01 00:00:00
abstract：PURPOSE:The cause of antibody positive pure red cell aplasia associated with the subcutaneous administration of EPREX to patients with chronic kidney failure has been determined to be due to the leaching of weakly adjuvant compounds from the uncoated rubber stoppers that were formerly used in prefilled syringes. Other ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5356-7
更新日期：2005-07-01 00:00:00
abstract：:The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016312827680
更新日期：1985-09-01 00:00:00
abstract：PURPOSE:To develop and subsequently evaluate a novel phase inversion-based method used to formulate lipidic nanocapsules. METHODS:Mechanical properties of emulsions prepared by multiinversion phase processes were investigated using a drop tensiometer. Based on the results obtained, a formulation process was developed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016121319668
更新日期：2002-06-01 00:00:00
abstract：PURPOSE:Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin. METHODS:A hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018908421434
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis (RA). Our aim was to apply a model-informed drug development (MIDD) approach to examine the totality of available clinical efficacy data. METHODS:Population pha...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2752-y
更新日期：2020-01-06 00:00:00
abstract：PURPOSE:Permeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera. METHODS:A vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2392-7
更新日期：2018-03-29 00:00:00
abstract：:The fluxes of nitroglycerine (NG) through human abdominal epidermis from different individuals were measured in vitro at 32°C. The mean NG flux for the entire group was 16.9 µg/cm(2) × hr, with a standard deviation of 47.7%. There are no significant differences in the means and the variances of NG fluxes between males...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016381017357
更新日期：1986-02-01 00:00:00
abstract：PURPOSE:To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. METHODS:Spray dried mannitol (SDM) partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1132-2
更新日期：2014-01-01 00:00:00
