Abstract：
PURPOSE:Models to predict membrane-water partition coefficients (Kp) as a function of drug structure, membrane composition, and solution properties would be useful. This study explores the partitioning of dexamethasone (Dex) and its ionizable 21-phosphate (Dex-P) in liposomes varying in acyl chain length, physical state, and pH. METHODS:DMPC:mPEG DMPE, DPPC:mPEG DPPE, and DSPC:mPEG DSPE (95:5 mol%) liposomes were prepared by thin film hydration. Kp values for Dex and Dex-P were determined from pH 1.5-8 by equilibrium dialysis and equilibrium solubility (Dex). RESULTS:Dex Kp values at 25°C were 705 ± 24, 106 ± 11, and 58 ± 9 in DMPC, DPPC, and DSPC, increasing to 478 ± 20 in DPPC liposomes at 45°C. Both neutral and anionic species contributed to the Kp of Dex-P versus solution pH (1.5-8). A linear correlation was found between the natural logarithm of Kp and the inverse of bilayer free surface area (1/afree) where afree is a parameter reflecting chain ordering that depends on bilayer composition and temperature. CONCLUSIONS:Models of the pH dependence of partitioning of ionizable compounds must include contributions of both neutral and ionized species. Bilayer free surface area may be an important variable to predict Kp of drug molecules versus lipid composition and temperature.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Modi S,Anderson BDdoi
10.1007/s11095-013-1143-zsubject
Has Abstractpub_date
2013-12-01 00:00:00pages
3154-69issue
12eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract：:The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018993610801
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1988-z
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:It is reported that the cerebrospinal fluid (CSF) to plasma unbound concentration ratio of fleroxacin at steady-state is approximately 0.5 in experimental animals. These results can be accounted for by assuming the presence of an active transport system for the efflux of this compound across the choroid plexus....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016081618149
更新日期：1996-04-01 00:00:00
abstract：PURPOSE:The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1021457911533
更新日期：2002-12-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)7m-beta-CD), and co-administration of a water-soluble polymer (HPMC) and cyclodextrins, on the oral bioavailability of glibenclamide in dogs. METHODS:Effects of cyclodextrins on the aqueous solubility of glibencl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011900527021
更新日期：1998-11-01 00:00:00
abstract：:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-007-9431-0
更新日期：2008-03-01 00:00:00
abstract：PURPOSE:In this study, we developed and evaluated a novel method to produce insulin-loaded hydrophilic microspheres allowing high encapsulation efficiency and the preservation of peptide stability during particle processing. The preparation method used the diffusion of water by an excess of solvent starting from a wate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000036919.94865.57
更新日期：2004-08-01 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：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:This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS:Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate g...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2464-8
更新日期：2018-08-09 00:00:00
abstract：:The dose dependency of carbamazepine pharmacokinetics was characterized in rats, a common test animal for antiepileptic drug efficacy. With a randomized Latin square schedule, 5, 10, and 20 mg/kg doses of carbamazepine were injected intravenously into six Sprague-Dawley rats followed by the administration of a 5 or 10...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015872901523
更新日期：1990-05-01 00:00:00
abstract：PURPOSE:VLPs displaying tumor targeting single-chain variable fragments (VLP-rscFvs) which targets tumor-associated glycoprotein-72 (TAG-72) marker protein have a potential for immunotherapy against colon carcinoma tumors. In this study, scFvs anchored on VLPs using glycosylphosphatidylinositol (GPI) were prepared to t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1316-4
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:To evaluate the transcellular mechanism of novel enhancers absorption enhancement of human growth hormone (hGH), by examining the involvement of a P-glycoprotein-like efflux system, changes in membrane fluidity, and membrane damage. METHODS:Caco-2 cell monolayers were grown on Snapwell filter supports and plac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014809916407
更新日期：1999-08-01 00:00:00
abstract：:The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sig...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880327911
更新日期：1992-07-01 00:00:00
abstract：:An on-line simultaneous assay for the enantiomers of verapamil (VA) and its three metabolites in plasma was developed with column-switching HPLC. This system consists of an ovomucoid protein chiral stationary phase coupled to an achiral reversed-phase column via a dilution tube and a trapping column. The reversed-phas...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015848806240
更新日期：1991-08-01 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:This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes. METHODS:After exposure of BHA and tBHQ to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9094-2
更新日期：2006-11-01 00:00:00
abstract：:Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatm...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018935420680
更新日期：1994-07-01 00:00:00
abstract：PURPOSE:To develop a streamlined strategy for pharmaceutical cocrystal preparation without knowledge of the stoichiometric ratio by preparing and characterizing the cocrystals of myricetin (MYR) with four cocrystal coformers (CCF). METHODS:An approach based on the phase solubility diagram (PSD) was used for MYR cocrys...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1443-y
更新日期：2015-01-01 00:00:00
abstract：:We describe an assay for acrolein in urine, employing derivatization with m-aminophenol in the presence of ferrous sulfate solution in sulfuric acid. The derivative (7-OH quinoline; DER) and the internal standard (quinine-bisulfate; IS) were separated on a 10-micron particle, 8 mm x 10-cm C18 cartridge in conjunction ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018964401677
更新日期：1993-11-01 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:Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012161630481
更新日期：1997-08-01 00:00:00
abstract：:Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using no...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880218535
更新日期：1991-07-01 00:00:00
abstract：:The effect of buprenorphine on bremazocine-induced diuresis was tested in the rat to determine the nature of buprenorphine's action at the ϰ opioid receptor. Both morphine-tolerant and naive rats were used to account for possible antidiuretic effects of buprenorphine at the µ site. Separate experiments established tha...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016340106299
更新日期：1985-07-01 00:00:00
abstract：PURPOSE:To investigate influence of ion induced mesophasic transformation on pharmaceutical performance of in situ gelling system consisting of glyceryl monooleate. METHODS:The prepared system showed mesophasic transformation during its conversion from sol to gel upon controlled hydration. The process of mesophasic tr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1033-4
更新日期：2013-07-01 00:00:00
abstract：PURPOSE:Understanding the mechanism of protein-excipient interaction and illuminating the influencing factors on protein stability are key steps in the rational design of protein formulations. The objective of this study was to assess effects of preferential interaction type of excipient and surface aromatic hydrophobi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2152-0
更新日期：2017-07-01 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：PURPOSE:This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic "nano-shields" and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactio...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1018-3
更新日期：2013-07-01 00:00:00
abstract：PURPOSE:The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the ther...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012114825513
更新日期：1997-06-01 00:00:00
abstract：PURPOSE:The growing amount of heterogeneous bioactivity data requires effective strategies to assess the promiscuity/selectivity of small-molecules and aid drug discovery. In the current study, we aim to evaluate the potential of assay profiles (APs, i.e., unique combinations of assay-related features describing how ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2523-1
更新日期：2018-10-18 00:00:00
