Abstract:
:Variability in the time to crystallization is a major technical and economic hurdle in using amorphous solids in dosage forms. It is hypothesized that amorphous solids "age", and that the older they are, the more relaxed they are and the higher the probability of crystallization. At present, there is no method that allows the "effective age" of an amorphous raw material to be assessed relative to its unrelaxed initial condition. A method has been developed that may satisfy this unmet need and provide a first step in subsequent investigation of the crystallization "event". This method consists of using master curves to enable the determination of the effective age ("aging") of an amorphous compound given normal excursions in storage conditions. The present study shows that master curves can be prepared for different storage conditions and subsequently be used to predict the relaxation or aging behavior of amorphous compounds with expected variations in storage conditions. Given the constraint that the system remain within the area enclosed by the equilibrium supercooled liquid line and the glass on the enthalpy-temperature diagram, experimental results using indomethacin and salicin as model compounds show that master curves can be used to predict aging behavior under nonisothermal conditions, with temperature excursions as large as 10 degrees C. The nonisothermal relaxation behavior can be modeled by combining the Kohlrausch-Williams-Watts (KWW) stretched exponential function, the relaxation function, and a shift factor. In addition, a model was developed that extends the range of applicability to time/temperature regions in which partial crystallization occurs.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Hilden LR,Morris KRdoi
10.1002/jps.10404subject
Has Abstractpub_date
2003-07-01 00:00:00pages
1464-72issue
7eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31269-2journal_volume
92pub_type
杂志文章abstract::This study describes the synthesis of a new generation of immunotoxins made by a noncovalent interaction between a monoclonal antibody derivatized with a dichlorotriazinic dye and the ribosomal inhibitor protein gelonin. The scheme of preparation has several advantages with respect to the traditional methods, which us...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830218
更新日期:1994-02-01 00:00:00
abstract::Plasma binding of chlordiazepoxide, diazepam, loraxepam, and oxazepam was determined by equilibrium dialysis in 20 male, healthy volunteers, 25-86 years old. A wide range of binding was observed, with the free fraction varying twofold for lorazepam, fourfold for chlordiazepoxide and diazepam, and over 20-fold for oxa...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600681034
更新日期:1979-10-01 00:00:00
abstract::Aerosolized medicine is one of the fastest growing areas in the pharmaceutical industry. Dry powder aerosols of pharmaceutical compounds are particularly attractive for the prevention and treatment of respiratory diseases but are also emerging as a treatment option for systemic diseases. Engineering particles in dry p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23168
更新日期:2012-09-01 00:00:00
abstract::Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Ph...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21026
更新日期:2008-02-01 00:00:00
abstract::By using data from a sample of 1767 community pharmacies, a total cost function was estimated by a polynomial regression of total cost on output. The Cobb-Douglas production function was estimated by a multiple linear regression of natural logarithmic transformations of output on natural logarithmic transformation of ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650208
更新日期:1976-02-01 00:00:00
abstract::An important part of pharmacokinetic research is fitting models to observed data and estimating the parameters in the model. In general, parameter estimation in pharmacokinetics is a subset of the general problem of nonlinear regression or parameter estimation in nonlinear regression models. The same criteria, algorit...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760716
更新日期:1987-07-01 00:00:00
abstract::Nonviral, plasmid-based therapeutics are a new class of pharmaceutical agents that offer the potential to cure many diseases that are currently considered untreatable. While nonviral vectors have shown promise in clinical trials, their physical instability in liquid formulations represents a major barrier to the devel...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/(SICI)1520-6017(200003)89:3<289::AID-JPS1>
更新日期:2000-03-01 00:00:00
abstract::Mebendazole (MBZ) is a common benzimidazole anthelmintic that exists in three different polymorphic forms, A, B, and C. Polymorph C is the pharmaceutically preferred form due to its adequated aqueous solubility. No single crystal structure determinations depicting the nature of the crystal packing and molecular confor...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21593
更新日期:2009-07-01 00:00:00
abstract::A radioimmunoassay procedure was developed for the antihistamine terfenadine (alpha[4-(1,2-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol). The keto analog of terfenadine was converted to its O-carboxymethyloxime derivative, which was conjugated to bovine thyroglobulin by a mixed anhydride techniq...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600691218
更新日期:1980-12-01 00:00:00
abstract::Two human bioavailability studies were conducted to assess the in vivo performances of recently marketed 200-, 300-, and 400-mg ibuprofen capsules relative to the innovator's 300- and 400-mg tablets when administered as single oral 300- or 400-mg doses. An ibuprofen oral solution was also administered in each trial. W...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710920
更新日期:1982-09-01 00:00:00
abstract::The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24137
更新日期:2014-11-01 00:00:00
abstract::The viscosity and surface tension of systems containing small amounts of salicylic acid in aqueous solutions of cetrimide were determined. An abrupt increase in viscosity was observed, and the molar ratio of salicylic acid to certrimide at which this viscosity increase occurred was 1:2. The surface tension of these sy...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600661236
更新日期:1977-12-01 00:00:00
abstract::The growing interest of pharmaceutical companies toward the crystal morphology prediction of active pharmaceutical ingredients is a consequence of the dramatic effect of the crystal habit on the tableting behavior of drugs. In order to help the optimization of the industrial process, molecular mechanics calculations t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23334
更新日期:2013-01-01 00:00:00
abstract::Product temperature (Tb) and drying time constitute critical material attributes and process parameters in the lyophilization process and especially during the primary drying stage. In the study, we performed a temperature measurement by the sublimation rate (TMbySR) to monitor the Tb value and determine the end point...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.02.015
更新日期:2019-07-01 00:00:00
abstract::The solubilization of five model hydrophobic drugs by a series of micelle-forming, water-soluble methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymers (MePEG-b-PCL) with varying methoxy poly(ethylene glycol) (MePEG) and polycaprolactone (PCL) block lengths was investigated. Variation of the feed weig...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21037
更新日期:2008-03-01 00:00:00
abstract::The tissue penetration and distribution of antibiotics is of great importance, since most of the infections occur in the tissue. At the infection site, the free, unbound fraction of the antibiotic is responsible for the antiinfective effect. These free extracellular concentrations can be measured by microdialysis. It ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js950304x
更新日期:1996-04-01 00:00:00
abstract::This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous proc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24252
更新日期:2015-03-01 00:00:00
abstract::Solubilization of nonpolar drugs constitutes one of the most important tasks in parenteral formulations design. This study investigates and assesses the solubility enhancement of Fluasterone by various techniques including cosolvency, micellization, and complexation. Of the solubilizing agents used, the modified beta-...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9901413
更新日期:1999-10-01 00:00:00
abstract::The in vitro release of physostigmine salicylate (PS) from a submicron emulsion and an aqueous solution was studied using the dialysis bag method. These formulations were then perfused to various locations along the rat small intestine (proximal, mid, and distal jejunum), and two lengths (10 and 55 cm). The disappeara...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800706
更新日期:1991-07-01 00:00:00
abstract::In drug release systems using hydrogels as carriers, the presence of the polymer network will reduce the drug release rate, which can extend the release period. For a controlled-release process of drug, usually the ideal situation is to get a zero-order drug release rate. In this paper, the mathematical model of hydro...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23497
更新日期:2013-05-01 00:00:00
abstract::The binding of Cu2+ and Ni2+ to bovine, dog, and human serum albumin has been studied by the 35Cl NMR probe technique. The number of primary copper sites were estimated to be 1.3 for human serum albumin, 3.1 for bovine serum albumin, and 6.6 for dog serum albumin. A similar number of primary nickel sites was determine...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740116
更新日期:1985-01-01 00:00:00
abstract::Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and F...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1016/j.xphs.2015.11.005
更新日期:2016-02-01 00:00:00
abstract::Because the ionized species is more polar than its un-ionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js980433o
更新日期:1999-05-01 00:00:00
abstract::To reduce the inherent variability in serum uric acid levels of animals allowed ad libitum exposure to food containing potassium oxonate and uric acid, male Sprague-Dawley rats were trained to eat their daily food allotment in a 1.25-hr period each morning. After training the rats were fed a food mixture containing 5%...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600680538
更新日期:1979-05-01 00:00:00
abstract::A new mucoadhesive tablet, which releases natural active agents for pain reduction and rapid healing of canker sores, has been prepared and characterized. Adhesive tablets were prepared by compression molding of mixed powders of crosslinked polyacrylic acid and hydroxypropyl cellulose, absorbed with citrus oil and mag...
journal_title:Journal of pharmaceutical sciences
pub_type: 临床试验,杂志文章
doi:10.1002/jps.20193
更新日期:2004-12-01 00:00:00
abstract::An analysis of the disintegration-dissolution sequence of drug release from a tablet leads to a mathematical expression relating disintegration to the dissolution profile of the tablet and the dissolution rate of the primary drug particles in the tablet. The equation describing the disintegration of an acetaminophen t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670122
更新日期:1978-01-01 00:00:00
abstract::Nasal administration as a means of delivering therapeutic agents preferentially to the brain has gained significant recent interest. While some substrates appear to be delivered directly to the brain via this route, the mechanisms governing overall brain uptake and exposure remain unclear. Some substrates utilize the ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.20318
更新日期:2005-06-01 00:00:00
abstract::The synthesis of diazoketone analogs of amino acids and associated problems were investigated with N-phthaloyl-DL-alanine serving as a model. The carboxyl was activated by conversion to the acid chloride or, under mild conditions, to the mixed anhydride obtained with ethyl chloroformate or dicyclohexylcarbodiimide; th...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670518
更新日期:1978-05-01 00:00:00
abstract::In this study, we investigated the potential roles of nanoparticles (<100 nm) and submicron (100-1000 nm) particles in the formation of microparticles (>1000 nm) in protein formulations under some pharmaceutically relevant stress conditions. Exposure of intravenous immunoglobulin solutions to the interface-associated ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.03.016
更新日期:2018-07-01 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