Abstract：
PURPOSE:To devise experimental and computational models to predict aqueous drug solubility. METHODS:A simple and reliable modification of the shake flask method to a small-scale format was devised, and the intrinsic solubilities of 17 structurally diverse drugs were determined. The experimental solubility data were used to investigate the accuracy of commonly used theoretical and semiexperimental models for prediction of aqueous drug solubility. Computational models for prediction of intrinsic solubility, based on lipophilicity and molecular surface areas, were developed. RESULTS:The intrinsic solubilities ranged from 0.7 ng/mL to 6.0 mg/ mL, covering a range of almost seven log10 units, and the values determined with the new small-scale shake flask method agreed well with published solubility data. Solubility data computed with established theoretical models agreed poorly with the experimentally determined solubilities, but the correlations improved when experimentally determined melting points were included in the models. A new, fast computational model based on lipophilicity and partitioned molecular surface areas, which predicted intrinsic drug solubility with a good accuracy (R2 of 0.91 and RMSEtr of 0.61) was devised. CONCLUSIONS:A small-scale shake flask method for determination of intrinsic drug solubility was developed, and a promising alternative computational model for the theoretical prediction of aqueous drug solubility was proposed.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Bergström CA,Norinder U,Luthman K,Artursson Pdoi
10.1023/a:1014224900524subject
Has Abstractpub_date
2002-02-01 00:00:00pages
182-8issue
2eissn
0724-8741issn
1573-904Xjournal_volume
19pub_type
杂志文章abstract：PURPOSE:The heparin-paclitaxel conjugates using amino acid as linker (HD2), with low anticoagulant activity, the similar anticancer activity as paclitaxel, offer great potential for further investigation. METHODS:Two types of heparin-paclitaxel conjugates (HD) have been developed, in which O-acetylated heparin as carr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9762-5
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS:Nanofibr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2428-z
更新日期：2018-05-22 00:00:00
abstract：:The technique of Affinity capillary electrophoresis (ACE) is a useful tool to characterize complexation and partition equilibria. A wide range of applications in pharmaceutics has been presented: the determination of pKA values, of association constants between drugs and cyclodextrins or amphiphilic compounds as well ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
abstract：BACKGROUND:Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability. METHODS:99mTc-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2548-5
更新日期：2018-11-29 00:00:00
abstract：PURPOSE:This work describes the synthesis of block co-polymeric micelles, methoxy-poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA) to encapsulate Curcumin (CUR), thereby improving the dispersibility and chemical stability of curcumin, prolonging its cellular uptake and enhancing its bioavailability. METHODS:CUR-mPEG...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1830-z
更新日期：2016-04-01 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:We have evaluated a new process, involving solution-enhanced dispersion by supercritical fluids (SEDS), for the production of polymeric microparticles. METHODS:The biodegradable polymers, Poly (DL-lactide-co-glycolide): copolymer composition 50:50 (DL-PLG), Poly (L-lactide) (L-PLA), Poly (DL-lactide) (DL-PLA) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018868423309
更新日期：1999-05-01 00:00:00
abstract：PURPOSE:Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9330-4
更新日期：2008-02-01 00:00:00
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...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1001-z
更新日期：2013-06-01 00:00:00
abstract：:Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015902308676
更新日期：1990-12-01 00:00:00
abstract：:Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015815614959
更新日期：1991-04-01 00:00:00
abstract：PURPOSE:To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. METHODS:The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-d...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1060-1
更新日期：2013-08-01 00:00:00
abstract：PURPOSE:There is evidence that cholesterol affects the ATPase and transport functions of P-glycoprotein (P-gp). To study the influence of cholesterol on P-gp in a well defined lipid environment, we reconstituted P-gp in egg phosphatidylcholine (PhC) and PhC/cholesterol proteoliposomes with negligible residual amounts o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9326-0
更新日期：2007-11-01 00:00:00
abstract：PURPOSE:To evaluate the effect of re-directing the uptake mechanism of polyplexes containing oligodeoxynucleotide (ODN) decoys to nuclear factor kappa B (NF-kappaB) from absorptive-mediated to receptor-mediated endocytosis. MATERIALS AND METHODS:Complexes of ODNs and a co-polymer of biotin-polyethylenglycol and polyet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9389-y
更新日期：2008-03-01 00:00:00
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 stat...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1143-z
更新日期：2013-12-01 00:00:00
abstract：:The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016251023427
更新日期：1995-01-01 00:00:00
abstract：:Photodegradation of solutions of metronidazole in the presence and absence of sodium urate was studied. Photodegradation appeared to follow zero-order kinetics and was found to be dependent on the pH, buffer species, sodium urate concentration, and light source. Complex formation between metronidazole and sodium urate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015851719579
更新日期：1989-01-01 00:00:00
abstract：PURPOSE:The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs) together are regarded as an organic cation transport system critical to the disposition and response of many organic cationic drugs. Patient response to the analgesic morphine, a characterized substrate for human OCT1, is highly v...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2526-y
更新日期：2018-10-25 00:00:00
abstract：PURPOSE:The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS:The anti-acne agent, adapalene, was encapsulated in acid-responsive polyme...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1398-z
更新日期：2014-11-01 00:00:00
abstract：PURPOSE:Following extracellular drug clearance, we analyzed the rate of doxorubicin efflux from the nucleus of three human leukemic cells (K562, Molt4 and CCRF-CEM) and related it to their differential sensitivity to this drug, after a short drug pulse. RESULTS:For many pulse-chase regimes, K562 cell viability was lea...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9369-2
更新日期：2007-11-01 00:00:00
abstract：:We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+aH+ + ko + kHO-aHO- and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015809408908
更新日期：1991-11-01 00:00:00
abstract：PURPOSE:The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. METHODS:A hydrophilic model molecule, inulin, was encapsulated within positively charged and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-4591-2
更新日期：2005-06-01 00:00:00
abstract：PURPOSE:To investigate the mechanisms involved in transport of sulfasalazine in Caco-2 cells. METHODS:Permeability coefficients of sulfasalazine and its analogs across Caco-2 cell monolayers were measured as a function of direction of transport, energy and concentration dependence, and in the presence of inhibitors of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026450326712
更新日期：2000-10-01 00:00:00
abstract：PURPOSE:Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011987423502
更新日期：1998-05-01 00:00:00
abstract：PURPOSE:To evaluate the effects of several buffers and excipients on the stability of glucagon during freeze-drying and storage as dried powder formulations. METHODS:The chemical and physical stability of glucagon in freeze-dried solid formulations was evaluated by a variety of techniques including mass spectrometry (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0820-7
更新日期：2012-12-01 00:00:00
abstract：PURPOSE:Exenatide, a potent insulinotropic agent, can be used for the treatment of non-insulin-dependent diabetes mellitus. However, the need for frequent injections seriously limits its therapeutic utility. The aim of present report was to develop an orally available exenatide formulation using goblet cell-targeting n...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1513-1
更新日期：2015-03-01 00:00:00
abstract：PURPOSE:The aim of this work was to investigate the influence of the oily nucleus composition on physico-chemical properties and anesthetic activity of poly (lactide-co-glycolide) nanocapsules with benzocaine. METHODS:Nanocapsules containing benzocaine were prepared with three different oily nucleus composition and ch...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0425-6
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:Cell penetrating peptides (CPPs) were widely used as motifs for drug delivery to tumor. In former study, an RGD reverse sequence dGR was used to develop active-targeting liposome R8dGR-Lip, which showed well penetrating ability and treatment efficiency on glioma model. However, recurrence after tumor resection ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2399-0
更新日期：2018-04-26 00:00:00
abstract：PURPOSE:To investigate the underlying cause for the observed differences in self-associating and viscoelastic behavior between two monoclonal antibodies, MAb1, and MAb2. METHODS:Several mutants were designed by swapping charged residues in MAb1 with those present in MAb2 at their respective positions and vice versa. R...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0410-0
更新日期：2011-07-01 00:00:00
abstract：PURPOSE:Percutaneous absorption assays of molecules for pharmaceutical and cosmetology purposes are important to determine the bioavailability of new compounds, once topically applied. The current method of choice is to measure the rate of diffusion through excised human skin using a diffusion cell. This method however...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1654-x
更新日期：2015-08-01 00:00:00
