Abstract：
PURPOSE:Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for organic compounds from the undercooled melt state. METHODS:Steady shear rate viscosities of numerous compounds were measured using standard rheometry as a function of temperature through the undercooled melt regime. Data for each compound were fit to the Vogel-Tamman-Fulcher (VTF) equation; kinetic fragility via strength parameter (D) was determined. RESULTS:Compounds with high crystallization tendencies exhibited lower melt viscosities than compounds with low crystallization tendencies. A correlation was observed between rate of change in viscosity with temperature and crystallization tendency, with slowly crystallizing compounds exhibiting larger increases in viscosity as temperature decreased below T(m). Calculated strength parameters indicated all compounds were kinetically fragile liquids; thus, kinetic fragility may not accurately assess glass-forming ability from undercooled melt state. CONCLUSIONS:A link was observed between the viscosity of a compound through the undercooled melt regime and its resultant crystallization tendency, indicating viscosity is a critical parameter to fully understand crystallization tendency of organic compounds.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Baird JA,Santiago-Quinonez D,Rinaldi C,Taylor LSdoi
10.1007/s11095-011-0540-4subject
Has Abstractpub_date
2012-01-01 00:00:00pages
271-84issue
1eissn
0724-8741issn
1573-904Xjournal_volume
29pub_type
杂志文章abstract：PURPOSE:Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery. METHODS:A sensitiv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1371-x
更新日期：2014-10-01 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：:A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018929531410
更新日期：1993-04-01 00:00:00
abstract：:The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018984121415
更新日期：1993-03-01 00:00:00
abstract：PURPOSE:To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method. METHODS:Fluorescein-labeled PEG nanocarriers of different molecular weights and shapes (linear, two-arm, four-arm, and eight-arm) were intraductally administ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0763-z
更新日期：2012-09-01 00:00:00
abstract：:5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the br...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015803922401
更新日期：1992-09-01 00:00:00
abstract：PURPOSE:This study compared gene expression profiles in mouse lungs after administration of the cationic polymers polyethyleneimine (PEI) or chitosan alone or formulated with a luciferase reporter plasmid (PEI-pLuc, chitosan-pLuc). METHODS:The polymers and formulations were administered intratracheally to Balb/c mice ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9563-7
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:A thermodynamic analysis of the binding to rat cortex adenosine A1 receptor of N6-substituted (full agonists) and N6-substituted-deoxyribose (partial agonists) adenosine derivatives was performed. The intrinsic activity of the compounds was evaluated by measurements of the inhibition of forskolin stimulated 3',...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018987816891
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4-10 fusion protein (IL4-10 FP) on in vitro and in vivo bioactivity and evaluated the effect of differential sialylation on pharmacokinetic param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2744-y
更新日期：2019-12-26 00:00:00
abstract：:Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. H...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018940122382
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:Near-infrared reflectance spectroscopy (NIRS) was used to evaluate and quantify the effect of compression force on the NIR spectra of tablets. METHODS:Flat, white tablets with no orientation (scoring, etc.) were manufactured on a Stokes Rotary Tablet Press. NIRS was used to predict tablet hardness on the follo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012071904673
更新日期：1997-01-01 00:00:00
abstract：PURPOSE:This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS:Plasma samples were collected at 1.5, 4, and 10 h after first oral ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2765-6
更新日期：2020-01-28 00:00:00
abstract：PURPOSE:HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2249-5
更新日期：2017-12-01 00:00:00
abstract：:Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmac...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-008-9646-8
更新日期：2009-01-01 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:Formulate phospho-sulindac (P-S, OXT-328) in a Pluronic hydrogel to be used as a topical anti-inflammatory agent and study its efficacy, safety and pharmacokinetics in an arthritis model. METHODS:LEW/crlBR rats with Freund's adjuvant-induced arthritis were treated with P-S formulated in Pluronic hydrogel (PSH)...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0953-8
更新日期：2013-06-01 00:00:00
abstract：PURPOSE:The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS:The erodible plugs were either prepared by direct compression followed by placing the tablets in...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011940718534
更新日期：1998-03-01 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
abstract：:Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016380104424
更新日期：1984-05-01 00:00:00
abstract：PURPOSE:To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. METHODS:To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0542-2
更新日期：2012-01-01 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：:Cholinesterases are ubiquitous carboxylesterase type B enzymes capable of hydrolyzing the neurotransmitter acetylcholine which are transiently expressed in multiple germline, embryonic, and tumor cells. The acute poisoning effects of various organophosphorous compounds are generally attributed to their irreversible co...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015867021628
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND METHODS...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1593-y
更新日期：2015-06-01 00:00:00
abstract：:In order to study the influence of hydrogen bonding in the amide backbone of a peptide on permeability across a cell membrane, a series of tetrapeptide analogues was prepared from D-phenylalanine. The amide nitrogens in the parent oligomer were sequentially methylated to give a series containing from one to four methy...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015867608405
更新日期：1992-03-01 00:00:00
abstract：PURPOSE:We have shown that the three human prostate xenograft tumors, i.e. the androgen-dependent CWR22 tumor, and the androgen-resistant CWR22R and CWR91 tumors, are comparable to patient tumors in their expression of prostate specific antigen, multidrug resistance p-glycoprotein, p53 and Bcl-2 and in their sensitivit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011921031564
更新日期：1998-11-01 00:00:00
abstract：PURPOSE:A theoretical study was performed to generate a pharmacophore model for chemically diverse structures that specifically interact with the diltiazem binding site of L-type calcium channels. METHODS:Via molecular mechanics and quantum chemical methods solvation energies, logP values, conformational and electroni...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015037800903
更新日期：1999-10-01 00:00:00
abstract：PURPOSE:The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. METHODS:Three baboons received CMS by IV infusion and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1716-0
更新日期：2015-10-01 00:00:00
abstract：PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020354809581
更新日期：2002-09-01 00:00:00
abstract：PURPOSE:Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2444-z
更新日期：2018-06-25 00:00:00
abstract：PURPOSE:A series of studies was conducted to evaluate the preclinical pharmacokinetics of SB-239063 (trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-[(2-methoxy)pyrimidin-4-yl] imidazole), a potent and selective p38 MAP kinase inhibitor. METHODS:SB-239063 was administered both i.v. and p.o. in the rat, dog, cynomol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013002414678
更新日期：2001-09-01 00:00:00
