Abstract：
:Physicochemical effects caused by intestinal fluids on drugs in the gastrointestinal (GI) tract can be a contributing factor in food induced changes in bioavailability. To identify physicochemical properties of gemfibrozil that may be altered by endogenous and dietary lipids, in vitro studies were conducted in model systems approximating the conditions of the upper GI tract. Factors examined include pH, solubility in bile salt micellar and mixed micellar systems with monoolein and lecithin, effect of fatty acids, dissolution, wetting, and partitioning in triglyceride dispersions. Gemfibrozil was solubilized by glycocholate solutions in a manner typical of other lipids and a three-fold increase in solubility was observed over physiologic concentrations. Addition of increasing amounts of swelling amphiphiles (monoolein, lecithin) to glycocholate solutions resulted in a linear increase in solubility. Fatty acid salts had no effect on gemfibrozil solubilization by micellar solutions. The dissolution rate of gemfibrozil increased slightly in the presence of glycocholate relative to buffer, however, addition of monoolein increased the dissolution rate three-fold. In triglyceride dispersions of mixtures of lipids, monoolein increased the fraction of drug in the micellar subphase, whereas fatty acid reduced it. The results indicate that in the conditions of the fed state gemfibrozil solubility and dissolution could be substantially increased relative to the conditions in the fasted state.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Luner PE,Babu SR,Radebaugh GWdoi
10.1023/a:1018967401000subject
Has Abstractpub_date
1994-12-01 00:00:00pages
1755-60issue
12eissn
0724-8741issn
1573-904Xjournal_volume
11pub_type
杂志文章abstract：PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000022410.89709.c3
更新日期：2004-04-01 00:00:00
abstract：PURPOSE:Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1024441702398
更新日期：2003-07-01 00:00:00
abstract：PURPOSE:To assess the blood-brain barrier (BBB) permeability of 12 clinically-used drugs in mdr1a(+/+) and mdr1a(-/-) mice, and investigate the influence of lipophilicity, nonspecific brain tissue binding, and P-gp-mediated efflux on the rate of brain uptake. METHODS:The BBB partition coefficient (PS) was determined u...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9876-4
更新日期：2009-07-01 00:00:00
abstract：PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitiz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2484-4
更新日期：2018-09-06 00:00:00
abstract：PURPOSE:This study aims to develop a characterization method for coating structure based on image analysis, which is particularly promising for the rational design of coated particles in the pharmaceutical industry. METHODS:The method applies the MATLAB image processing toolbox to images of coated particles taken with...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9805-y
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:One of the major hurdles facing nanomedicines is the antibody production against nanoparticles that subsequently results in their opsonization and clearance by macrophages. The objective of this research was to examine and identify the sequence of a low-immunogenic peptide based on recombinant elastin-like poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1683-5
更新日期：2015-09-01 00:00:00
abstract：:During protein lyophilization, it is common practice to complete the freezing step as fast as possible in order to avoid protein denaturation, as well as to obtain a final product of uniform quality. We report a contradictory observation made during lyophilization of recombinant tissue-type plasminogen activator (t-PA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016270103863
更新日期：1995-01-01 00:00:00
abstract：:Animal models are used commonly in various stages of drug discovery and development to aid in the prospective assessment of drug-drug interaction (DDI) potential and the understanding of the underlying mechanism for DDI of a drug candidate. In vivo assessments in an appropriate animal model can be very valuable, when ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-010-0157-z
更新日期：2010-09-01 00:00:00
abstract：PURPOSE:Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS:In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tob...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1361-z
更新日期：2014-10-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1010914624111
更新日期：2001-08-01 00:00:00
abstract：PURPOSE:Solid dispersions (SDs) represent the most common formulation technique used to increase the dissolution rate of a drug. In this work, the three most common methods used to prepare SDs, namely spray-drying, solvent-casting and freeze-drying, have been compared in order to investigate their effect on increasing ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2778-1
更新日期：2020-02-19 00:00:00
abstract：:Inkjet printing is an attractive material deposition and patterning technology that has received significant attention in the recent years. It has been exploited for novel applications including high throughput screening, pharmaceutical formulations, medical devices and implants. Moreover, inkjet printing has been imp...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-1931-3
更新日期：2016-08-01 00:00:00
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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：:The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018977021183
更新日期：1992-02-01 00:00:00
abstract：PURPOSE:Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. METHODS:Pharmacokinet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2458-6
更新日期：2018-07-30 00:00:00
abstract：PURPOSE:Induction of cell-mediated immune (CMI) responses is crucial for vaccine-mediated protection against difficult vaccine targets, e.g., Chlamydia trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune responses, but many marketed adjuvants stimulate predominantly humoral immune response...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2180-9
更新日期：2017-08-01 00:00:00
abstract：PURPOSE:Tissue partitioning is an important component of drug distribution and half-life. Protein binding and lipid partitioning together determine drug distribution. METHODS:Two structure-based models to predict partitioning into microsomal membranes are presented. An orientation-based model was developed using a mem...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2085-z
更新日期：2017-03-01 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
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018866611555
更新日期：1999-01-01 00:00:00
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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:The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even tho...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2300-6
更新日期：2018-02-21 00:00:00
abstract：PURPOSE:It was the aim of this study to synthesize and characterize a novel chitosan-glutathione (GSH) conjugate providing improved mucoadhesive and permeation-enhancing properties. METHODS:Mediated by carbodiimide and N-hydroxysuccinimide, glutathione was covalently attached to chitosan via the formation of an amide ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6248-6
更新日期：2005-09-01 00:00:00
abstract：:The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both local...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016250422596
更新日期：1995-02-01 00:00:00
abstract：PURPOSE:To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS:A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9852-z
更新日期：2009-06-01 00:00:00
abstract：:Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015973425708
更新日期：1988-08-01 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：PURPOSE:The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleoti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1965-6
更新日期：2016-09-01 00:00:00
abstract：PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016225707807
更新日期：1995-09-01 00:00:00
abstract：PURPOSE:Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. METHODS:To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9139-6
更新日期：2007-01-01 00:00:00
abstract：PURPOSE:To quantitatively compare in vitro dissolution data in biorelevant and compendial media, to investigate whether in vitro differences are reflected in the simulated plasma profile and to specify under which circumstances prediction of the plasma profile of orally administered lipophilic drugs can be achieved. M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011071401306
更新日期：2001-03-01 00:00:00
