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 materials were utilized to create spray-dried dispersions (SDDs) of drug and polymer, and these were tested for drug form and homogeneity. Dispersions were tested in vitro for their ability to achieve and maintain drug supersaturation, for a variety of drug structures. RESULTS:Of the 41 materials tested, HPMCAS was the most effective at maintaining drug supersaturation. Drug/HPMCAS SDDs were consistently more effective at achieving and maintaining drug supersaturation in vitro than were SDDs prepared with other polymers. Drug/HPMCAS SDDs were effective in vitro for eight low solubility drugs of widely varying structure. Drug/HPMCAS SDDs were more effective at achieving and maintaining supersaturation than were rotoevaporated Drug/HPMCAS dispersions or physical mixtures of Drug and HPMCAS. The degree of achievable drug supersaturation increased with increasing polymer content in the SDD. The drug in Drug /HPMCAS SDDs was amorphous, and the dispersions were demonstrated to have a single glass transition and were thus homogeneous. CONCLUSION:HPMCAS has been identified as a uniquely effective polymer for use in SDDs of low solubility drugs, with broad applicability across a variety of drug structures and properties.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Curatolo W,Nightingale JA,Herbig SMdoi
10.1007/s11095-009-9852-zsubject
Has Abstractpub_date
2009-06-01 00:00:00pages
1419-31issue
6eissn
0724-8741issn
1573-904Xjournal_volume
26pub_type
杂志文章abstract：:RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has th...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-011-0608-1
更新日期：2011-12-01 00:00:00
abstract：:Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multipl...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-017-2333-x
更新日期：2018-02-15 00:00:00
abstract：PURPOSE:The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs. METHODS:Preparation of the bicarbonate-containing dissolution medium was monitored by use...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026147620304
更新日期：2003-10-01 00:00:00
abstract：PURPOSE:In the present work, we developed water-in-oil (w/o) nanoemulsions for the intravesical administration of cisplatin. METHODS:The nanoemulsions were made up of soybean oil as the oil phase and Span 80, Tween 80, or Brij 98 as the emulsifier system. alpha-Terpineol and oleic acid were incorporated as permeation ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9947-6
更新日期：2009-10-01 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: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:At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs wit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2189-0
更新日期：2017-09-01 00:00:00
abstract：PURPOSE:The cause of antibody positive pure red cell aplasia associated with the subcutaneous administration of EPREX to patients with chronic kidney failure has been determined to be due to the leaching of weakly adjuvant compounds from the uncoated rubber stoppers that were formerly used in prefilled syringes. Other ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5356-7
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7147-6
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:This study was designed to investigate the stability of recombinant FVIII (rFVIII) in solution at different pHs and to probe the cause(s) of rFVIII inactivation under accelerated storage conditions. METHODS:Aqueous stability samples of full-length rFVIII at different pHs were incubated at 40 degrees C for seve...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023271405005
更新日期：2003-04-01 00:00:00
abstract：PURPOSE:The present study evaluates immobilized artificial membrane (IAM) chromatography for predicting drug permeability across the blood-brain barrier (BBB) and outlines the potential and limitations of IAMs as a predictive tool by comparison with conventional methods based on octanol/water partitioning and octadecyl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011904311149
更新日期：1998-08-01 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:A patient was denoted to be generic brittle (GB) if they had a negative opinion about generics (e.g. prior history of a switch problem) or took the innovator brand of their most problematic anti-epileptic drug (AED) when generic was available. The aim of this hypothesis-generating study was to assess possible g...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2781-6
更新日期：2020-02-26 00:00:00
abstract：:Chemoembolization using microspheres of 100- to 200-microns is a useful way to treat primary and secondary hepatic tumors. In a search for a better embolic material, we described in detail the preparation and characterization of a poly(benzyl l-glutamate) (PBLG) microspheres containing cisplatin (CDDP). We determined ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018979703726
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0459-9
更新日期：2011-09-01 00:00:00
abstract：PURPOSE:Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018910200420
更新日期：1999-11-01 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:The purpose of this study was to clarify the localization and function of the ATP-binding cassette transporter G2 (ABCG2; BCRP/MXR/ABCP) in retinal capillary endothelial cells, which form the inner blood-retinal barrier, as an efflux transport system. METHODS:The expression was determined by reverse transcript...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0067-2
更新日期：2006-06-01 00:00:00
abstract：:The plasma concentration-time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015810019076
更新日期：1991-03-01 00:00:00
abstract：PURPOSE:E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 beta and TNF-alpha, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, SLex). In order to investiga...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018849029727
更新日期：1999-02-01 00:00:00
abstract：PURPOSE:To assess the uridine diphosphate (UDP)-glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of niflumic acid in human liver. METHODS:The glucuronidation activity of niflumic acid was determined in liver microsomes and recombinant UGT isozymes by incubation of niflumic acid with UDP-glucuroni...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0250-5
更新日期：2006-07-01 00:00:00
abstract：:Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s11095-018-2488-0
更新日期：2018-09-05 00:00:00
abstract：:Knowledge of comparative solubility profiles of a base and its hydrochloride salt is important in selecting one form over the other for dosage form design. The studies with two model bases, namely, tiaramide and papaverine, showed that, except during phase transition from a base to a salt or vice versa, the pH-solubil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016382426347
更新日期：1985-03-01 00:00:00
abstract：PURPOSE:Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that trave...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1531-z
更新日期：2015-04-01 00:00:00
abstract：PURPOSE:To develop a semi-physiological-based model describing simultaneously the time course of immature and mature B-lymphocytes after topotecan (TPT) administration to tumor-bearing rats. METHODS:Twenty-four tumor-bearing BDIX male rats received a single 6 mg/kg intra-peritoneal dose of TPT or saline. Mature and im...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0025-x
更新日期：2010-03-01 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：:Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influenc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0951-x
更新日期：2013-03-01 00:00:00
abstract：PURPOSE:4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1912-6
更新日期：2016-07-01 00:00:00
abstract：:Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018973530443
更新日期：1993-06-01 00:00:00
abstract：PURPOSE:To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading densi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9923-1
更新日期：2009-09-01 00:00:00
