Abstract:
:In this study, the influence of the preparation technique (ball milling, spray drying, and film casting) of a supersaturated amorphous dispersion on the quality of solubility determinations of indomethacin in polyvinylpyrrolidone was investigated by means of statistical analysis. After annealing of the amorphous dispersions above the crystallization temperature for 2 h, the solubility curve was derived from the glass transition temperature of the demixed material using the Gordon-Taylor relationship and fitting with the Flory-Huggins model. The study showed that the predicted solubility from the ball-milled mixtures was not consistent with those from spray drying and film casting, indicating fundamental differences between the preparation techniques. Through formal statistical analysis, the best combination of fit to the Flory-Huggins model and reproducibility of the measurements was analyzed. Ball milling provided the best reproducibility of the three preparation techniques; however, an analysis of residuals revealed a systematic error. In contrast, film casting demonstrated a good fit to the model but poor reproducibility of the measurements. Therefore, this study recommends that techniques such as spray drying or potentially film casting (if experimental reproducibility can be improved) should be used to prepare the amorphous dispersions when performing solubility measurements of this kind.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Knopp MM,Olesen NE,Holm P,Löbmann K,Holm R,Langguth P,Rades Tdoi
10.1002/jps.24207subject
Has Abstractpub_date
2015-01-01 00:00:00pages
44-51issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30246-Xjournal_volume
104pub_type
杂志文章abstract::Time and resource constraints necessitate increasingly early decision making to accelerate or stop preclinical drug discovery programs. Early discovery drug candidates may be potent inhibitors of new targets, but all too often exhibit poor pharmaceutical and pharmacokinetic properties that limit the in vivo exposure. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22092
更新日期:2010-07-01 00:00:00
abstract::Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Althou...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21534
更新日期:2009-04-01 00:00:00
abstract::The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characte...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600790116
更新日期:1990-01-01 00:00:00
abstract::Microparticles are of considerable interest for drug delivery, vaccination and diagnostic imaging. In order to obtain microparticles with long circulation times, or to provide the prerequisite for tissue specific targeting through decoration with suitable ligands, their surfaces need to be modified such that they beco...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.21350
更新日期:2008-11-01 00:00:00
abstract::The organic anion-transporting polypeptide (OATP) 2B1 which is ubiquitously expressed in the human body is assumed to play an important role in the cellular uptake of many drugs. Although the expression and function of this solute carrier transporter is well characterized in the human liver and other tissues, little i...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.04.001
更新日期:2017-09-01 00:00:00
abstract::A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970451q
更新日期:1998-08-01 00:00:00
abstract::A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor wi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22117
更新日期:2010-09-01 00:00:00
abstract::The conditions of sorption of penicillins and cephalosporins on nonionic macroporous copolymers of styrenedivinylbenzene were evaluated. By increasing the methanol concentration in the eluent, the sorption decreased. Salts exerted little influence on sorption. However, pH exerted a remarkable effect on sorption, and t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700906
更新日期:1981-09-01 00:00:00
abstract::Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.03.006
更新日期:2019-08-01 00:00:00
abstract::Oxidation of 7,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline with potassium permanganate in acetone afforded 7,8-dimethoxy-3,4-dihydroisoquinoline as the primary product. Hence, oxidation of the appropriate secondary nonphenolic 7,8-dioxygenated tetrahydroisoquinoline alkaloid is thus a facile method for the generation o...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600731137
更新日期:1984-11-01 00:00:00
abstract::It is understood that a potential issue for drugs with poor aqueous solubility is low oral absorption. If oral exposure issues arise when working with a low solubility drug candidate, the common action is to rely on enabling formulations to solve the issue. However, this approach becomes troublesome in the pre-clinica...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.04.003
更新日期:2016-06-01 00:00:00
abstract::The stability of highly purified supercoiled plasmid DNA formulated in simple phosphate or Tris-buffered saline solutions has been characterized to establish the overall degradation processes that occur during storage in aqueous solution. Plasmid DNA stability was monitored during accelerated stability studies (at 50 ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/(SICI)1520-6017(200001)89:1<76::AID-JPS8>3
更新日期:2000-01-01 00:00:00
abstract::The present study aimed to develop optimized quercetin (QT)-loaded self-nanoemulsifying drug delivery system (SNEDDS) that offers protective effect against liver damage. Solubility study of QT in different oils, surfactants, and cosurfactants was performed. Ternary phase mixtures of the selected components were constr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23834
更新日期:2014-02-01 00:00:00
abstract::Diazepam (1), a hypnotic and anxiolytic drug in worldwide use, formed an intermediate product in a mixture of ethanol and sodium hydroxide ([NaOH] > or = 1 M). The intermediate product slowly decomposed to form 2-(methylamino)-5-chlorobenzophenone imine (2) and 2-(methylamino)-5-chlorobenzophenone (3). The amount of 2...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9504245
更新日期:1996-07-01 00:00:00
abstract::Previous studies from this laboratory suggested that a solution model (Flory-Huggins equation) modified by a free volume model (Vrentas equation) could satisfactorily describe water absorption into an amorphous solid composed of a sugar or a polymer. This paper has extended the studies of single solutes to binary mixt...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.1090
更新日期:2001-09-01 00:00:00
abstract::Injectable microcapsules containing 75% (w/w) cyclazocine, a narcotic antagonist, were prepared with dl-poly(lactic acid) as the coating material. Capsule fractions falling between 105 and 295 mum released about 90% of their cyclazocine in 8 days of rotating-bottle extraction at 37 degrees in pH 7.4 phosphate buffer. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650612
更新日期:1976-06-01 00:00:00
abstract::In this study, the adsorption of an IgG1 antibody to siliconized vials was investigated with focus on the formulation parameters pH, ionic strength, and nonionic surfactants. Electrophoretic mobility measurements were performed to investigate the charge characteristics of protein and siliconized glass particles at dif...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24239
更新日期:2015-01-01 00:00:00
abstract::Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This pl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.03.005
更新日期:2017-07-01 00:00:00
abstract::The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were pr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21609
更新日期:2009-09-01 00:00:00
abstract::Dabrafenib is a small-molecule inhibitor of BRAF kinase activity that is currently being developed for the treatment of BRAF V600 mutation-positive melanoma. This clinical, open-label, two-cohort (n = 14 per cohort), randomized study was designed to evaluate the effect of drug substance particle size, and food on the ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,随机对照试验
doi:10.1002/jps.23519
更新日期:2013-09-01 00:00:00
abstract::Porcine gelatins have been widely used as stabilizers of macromolecular based pharmaceuticals but the mechanism by which they stabilize has not been precisely established. Their variability and immunogenicity, however, make them less than ideal excipients. In this work, we take advantage of the availability of recombi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20980
更新日期:2007-12-01 00:00:00
abstract::A high-pressure liquid chromatographic method for the sensitive, rapid, and specific determination of sulfapyridine and its N-acetyl derivative in plasma and saliva was developed. A cyano-bonded, reversed-phase, high efficiency column was used. The system detected these sulfonamides in serum to 0.25 mg/liter and withi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670916
更新日期:1978-09-01 00:00:00
abstract::RNA interference has emerged as a potentially powerful tool in the treatment of genetic and acquired diseases by delivering short interfering RNA (siRNA) or microRNA (miRNA) to target genes, resulting in their silencing. However, many physicochemical and biological barriers have to be overcome to obtain efficient in v...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.23300
更新日期:2012-11-01 00:00:00
abstract::Human papillomavirus (HPV) virus-like-particles (VLPs) produced by recombinant expression systems are promising vaccine candidates for prevention of cervical cancers as well as genital warts. At high protein concentrations, HPV VLPs, comprised of the viral capsid protein L1 and expressed and purified from yeast, are p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20377
更新日期:2005-07-01 00:00:00
abstract::The kinetic barrier against the transport of methyl and ethyl nicotinates across the water-isopropyl myristate interface has been studied as a function of temperature using a rotating diffusion cell. The temperature dependence of the interfacial transfer kinetics has enabled calculation of the thermodynamic parameters...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600720212
更新日期:1983-02-01 00:00:00
abstract::A new method for determining a quaternary mixture of vitamins B6, B1, and B12 and uridine 5'-triphosphate (UPT) using second-derivative spectrophotometry is described. Calibration graphs were linear up to 30 micrograms/mL of vitamin B6 at 307 nm (r = 0.9999) and vitamin B1 at 282.7 nm (r = 0.9997) and up to 35 microgr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600840109
更新日期:1995-01-01 00:00:00
abstract::A highly sensitive and specific electron-capture GLC assay capable of detecting picogram quantities of metoclopramide, a procaine derivative, in biological fluids was developed. This assay consisted of extracting metoclopramide from an alkalinized aqueous layer into benzene. A portion of the organic phase was derivati...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670813
更新日期:1978-08-01 00:00:00
abstract::The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid be...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830327
更新日期:1994-03-01 00:00:00
abstract::Conjunctiva occupies most of the ocular surface area, and conjunctival permeability affects ocular and systemic drug absorption of topical ocular medications. Therefore, the aim of this study was to obtain a computational in silico model for structure-based prediction of conjunctival drug permeability. This was done b...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.04.061
更新日期:2017-09-01 00:00:00
abstract::Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the sa...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600781012
更新日期:1989-10-01 00:00:00