Abstract：
:Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Hakkarainen JJ,Jalkanen AJ,Kääriäinen TM,Keski-Rahkonen P,Venäläinen T,Hokkanen J,Mönkkönen J,Suhonen M,Forsberg MMdoi
10.1016/j.ijpharm.2010.09.016subject
Has Abstractpub_date
2010-12-15 00:00:00pages
27-36issue
1-2eissn
0378-5173issn
1873-3476pii
S0378-5173(10)00717-9journal_volume
402pub_type
杂志文章abstract：:Leachability of the plasticizer di(2-ethylhexyl) phthalate (DEHP) from administration sets into intravenous parenteral emulsions containing fat was investigated. DEHP is added to polyvinyl chloride (PVC) to impart flexibility. However, DEHP is a lipid-soluble suspected carcinogen that is hepatotoxic and teratogenic in...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/s0378-5173(03)00335-1
更新日期：2003-08-27 00:00:00
abstract：:The aptitude of ropinirole to permeate the buccal tissue was tested using porcine mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation was also evaluated in presence of various penetration enhancers and in iontophoretic conditions. Ropinirole, widely used in treatment of motor fluctuations of...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2012.03.022
更新日期：2012-06-15 00:00:00
abstract：:Hot-melt extrusion has attracted considerable interest within the pharmaceutical industry. However, there remains some uncertainty as to how to characterise the physical structure of the extruded systems, particularly in terms of identifying the nature of the drug dispersion within the polymer. The aim of the study wa...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2007.11.048
更新日期：2008-04-16 00:00:00
abstract：:How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japa...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章,评审
doi：10.1016/j.ijpharm.2020.119491
更新日期：2020-09-25 00:00:00
abstract：:Poor water solubility, short half-life, and low drug efficacy posed a challenge for clinical application of curcumin (CUR). In this work, a kind of CUR prodrug was synthesized by coupling two CUR molecules with a mono-thioether linker for glutathione (GSH)-responsive drug delivery. The synthesized CUR prodrug (CUR-S-C...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2018.07.061
更新日期：2018-10-05 00:00:00
abstract：:This investigation has examined possible causes of the poor bioavailability of the beta(3)-adrenoceptor agonist BTA-243. The aqueous solubility of BTA-243 is pH dependent with a solubility minimum at pH 1.5. However, the dissolution rate of the disodium salt of BTA-243 is similar at both pH 2.0 and 7.4 indicating that...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/s0378-5173(00)00657-8
更新日期：2001-02-01 00:00:00
abstract：:In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorl...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2004.12.017
更新日期：2005-04-11 00:00:00
abstract：:We have evaluated a miniaturized in vitro method, based on the μDISS Profiler™ technique that enables on-line monitoring of drug release from a 21 μl sample with 10 ml of release medium. Four model drugs in eight clinically used formulations, including both solid and non-solid drug delivery systems, were investigated....
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2015.03.076
更新日期：2015-01-01 00:00:00
abstract：:The buccal administration of ergotamine tartrate (ET) combined with polyvinyl alcohol (PVA) gel brought about higher plasma concentration of ET compared with that of oral administration of capsules in guinea-pigs. T(max) of ET in plasma of buccal administration was significantly smaller than that of oral administratio...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/s0378-5173(02)00070-4
更新日期：2002-05-15 00:00:00
abstract：:Cinnarizine was loaded in the lipid emulsion to develop an intravenous formulation with good physical and chemical stability. High-pressure homogenization was used to prepare the lipid emulsion. The factors influencing the stability of cinnarizine lipid emulsion, such as different drug loading methods, pH, temperature...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2009.02.006
更新日期：2009-05-21 00:00:00
abstract：:Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the reso...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2011.01.023
更新日期：2011-04-04 00:00:00
abstract：:A novel drug delivery system (DDS) with sustained release properties was developed to allow ocular protein delivery. The DDS developed is aimed at overcoming stability issues during preparation such as denaturation of proteins caused by shear forces applied or due to elevated temperatures and air entrapment potentiall...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2015.01.042
更新日期：2015-03-15 00:00:00
abstract：:The self-organizing complexes with hyaluronic acid (HA) and polydopamine (PDA), an adhesion mediator via hydrogen bonding, were investigated for use as protein drug carriers. The complexes were prepared with HA of different molecular weights (20 kDa and 200 kDa) and various molar ratios of dopamine and lysozyme, a mod...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2018.03.007
更新日期：2018-05-05 00:00:00
abstract：:The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin-doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract ...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2018.04.052
更新日期：2018-07-10 00:00:00
abstract：:We investigated the feasibility of preparing high-potency tacrolimus dry powder for inhalation using thin film freezing (TFF). We found that using ultra-rapid freezing can increase drug loading up to 95% while maintaining good aerosol performance. Drug loading affected the specific surface area and moisture sorption o...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2020.119490
更新日期：2020-08-30 00:00:00
abstract：:Three-dimensional printing (3DP) is a highly disruptive technology with the potential to change the way pharmaceuticals are designed, prescribed and produced. Owing to its low cost, diversity, portability and simplicity, fused deposition modeling (FDM) is well suited to a multitude of pharmaceutical applications in di...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章,评审
doi：10.1016/j.ijpharm.2018.07.024
更新日期：2018-09-05 00:00:00
abstract：:Low dose micro-tablets with acceptable quality attributes, specifically content uniformity (CU), would not only enhance the dose flexibility in the clinic, but also decrease excipient burden in pediatric population. Considering the CU challenges associated with directly compressed low dose micro-tablets, in this study...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2020.119571
更新日期：2020-09-25 00:00:00
abstract：:A range of 17 ternary formulations of itraconazole (ITZ), HPMCP and Soluplus have been manufactured using spray drying. These amorphous solid dispersions (ASDs) were very stable against crystallisation and ITZ was found to be amorphous in all formulations after one year at 40°C/75% RH. A number of solid state analytic...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2017.01.043
更新日期：2017-03-15 00:00:00
abstract：:The pharmacokinetic behavior of Gastrodin in rat plasma and cerebrospinal fluid (CSF) after intranasal and intravenous administration (50mg kg(-1)) was investigated. Intranasal administration of Gastrodin provided a comparable AUC in CSF compared with the intravenous administration. But Gastrodin level in plasma was v...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2007.03.041
更新日期：2007-08-16 00:00:00
abstract：:A simple and rapid method for radiolabeling of three types of Ag NPs has been performed using 125I isotope, with high labeling yields, >90% without disturbing the optical properties. All the factors affecting labeling yield were studied. In order to monitor the in-vivo tissue uptake of radiolabeled Ag NPs using γ-rays...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2017.06.044
更新日期：2017-08-30 00:00:00
abstract：:To study the usefulness of glycerin fatty acid ester Poem TR-FB (TR-FB) and Poem TR-HB (TR-HB) as lubricants, pressure transmission ratio, ejection force, disintegration time, and tensile strength were measured at different concentrations and mixing times for granules and tablets. When each lubricant was mixed at 0.1-...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2009.11.001
更新日期：2010-02-15 00:00:00
abstract：:In this work calcium stearate (CaSt) multi-particulates loaded with codeine phosphate (COP) were developed in an attempt to provide extended release (ER) combined with alcohol dose dumping (ADD) resistance. The pellets were prepared via wet/extrusion spheronization and ER characteristics were obtained after fluid bed ...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2016.05.049
更新日期：2016-07-25 00:00:00
abstract：:Andrographolide (AG) is a chemical entity from traditional Chinese herbs and its oral pills have been applied to the treatment of respiratory inflammation. Here we report pulmonary delivery of liposomal AG dry powder inhalers (LADPIs) for treatment of Staphylococcus aureus-induced pneumonia. AG liposomes were prepared...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2017.06.005
更新日期：2017-08-07 00:00:00
abstract：:The use of non-linear mixed effects models to describe dissolution data has been evaluated. A theoretical part is included to introduce this approach to scientists who are not familiar with this type of statistics. The standard settings of the statistical software package (S-plus) are used as much as possible. Several...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/s0378-5173(02)00127-8
更新日期：2002-06-20 00:00:00
abstract：:Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to ...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2011.11.046
更新日期：2012-02-28 00:00:00
abstract：:The short half-life and bitter taste of carbinoxamine maleate2 (CAM) lead to poor compliance by pediatric patients who are being treated for allergic rhinitis. To address these issues, carbinoxamine-resin complexes3 (CRCs) were prepared by ion exchange and then coated with Kollicoat SR 30D. The resultant microencapsul...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2020.119779
更新日期：2020-10-15 00:00:00
abstract：:To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic F127-g-poly(acrylic acid) copolymers were studied as in situ gelling vehicle for ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels were investigated. The...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2007.09.005
更新日期：2008-02-28 00:00:00
abstract：:A calibration strategy for the continuous monitoring of solvent-mediated phase transition was developed using in situ Raman spectroscopy. Citric acid which exhibits enantiotropy during its anhydrous/monohydrate phase transition was selected as a model organic product. Using 25 samples in suspension, specific calibrati...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2005.10.009
更新日期：2006-01-13 00:00:00
abstract：:Pharmaceutical containers for parenterals have been predominantly manufactured using glass as a packaging material of choice, especially Type-I glass, since it has been regarded as a chemically inert and an effective container closure system (CCS). Nevertheless, there have been reports and recalls related to glass qua...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2019.118510
更新日期：2019-09-10 00:00:00
abstract：:Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI-MNPs)...
journal_title：International journal of pharmaceutics
pub_type： 杂志文章
doi：10.1016/j.ijpharm.2016.01.054
更新日期：2016-03-30 00:00:00
