Abstract：
:Elucidation of the most stable form of an active pharmaceutical ingredient (API) is a critical step in the development process. Polymorph screening for an API with a complex polymorphic profile can present a significant challenge. The presented case illustrates an extensively polymorphic compound with an additional propensity for forming stable solvates. In all, 5 anhydrous forms and 66 solvated forms have been discovered. After early polymorph screening using common techniques yielded mostly solvates and failed to uncover several key anhydrous forms, it became necessary to devise new approaches based on an advanced understanding of crystal structure and conformational relationships between forms. With the aid of this analysis, two screening approaches were devised which targeted high-temperature desolvation as a means to increase conformational populations and enhance overall probability of anhydrous form production. Application of these targeted approaches, comprising over 100 experiments, produced only the known anhydrous forms, without appearance of any new forms. The development of these screens was a critical and alternative approach to circumvent solvation issues associated with more conventional screening methods. The results provided confidence that the current development form was the most stable polymorph, with a low likelihood for the existence of a more-stable anhydrous form.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Campeta AM,Chekal BP,Abramov YA,Meenan PA,Henson MJ,Shi B,Singer RA,Horspool KRdoi
10.1002/jps.22230subject
Has Abstractpub_date
2010-09-01 00:00:00pages
3874-86issue
9eissn
0022-3549issn
1520-6017pii
S0022-3549(15)32491-6journal_volume
99pub_type
杂志文章abstract：:Apparent micellar molecular weights were determined with the antibiotic fusidate sodium by ultracentrifugation in varying counterion concentrations (Na+). The effects of buffer salts, pH, sodium chloride concentration, and drug concentration were studied. The results strongly support the concept of the formation of pr...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600640536
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abstract：:The delivery of drugs via the mucous membranes lining the oral cavity (i.e., sublingual and buccal), with consideration of both systemic delivery and local therapy, is reviewed in this paper. The structure and composition of the mucosae at different sites in the oral cavity, factors affecting mucosal permeability, pen...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.2600810102
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doi：10.1002/jps.2600831214
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600710710
更新日期：1982-07-01 00:00:00
abstract：:The solubility equation of Yalkowsky was used to estimate the aqueous solubility of 33 barbiturates in the temperature range of 5 to 45 degrees C. The equation was extended by adding a term which accounts for the effect of pH on the solubility of the drug. The extended equation is successful in estimating the aqueous ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760120
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pub_type： 杂志文章,评审
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600670344
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abstract：:The spherically agglomerated crystals of aminophylline (theophylline-ethylenediamine complex) can be compounded directly into pharmaceutical formulations without further processing, e.g., granulation. Such crystals were prepared by mixing theophylline and ethylenediamine in a partially miscible solvent system, i.e., o...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731021
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abstract：:The dissolution kinetics of theophylline monohydrate and anhydrous theophylline were investigated with a rotating-disk apparatus in buffer solutions at 298 K under sink conditions. The observed dissolution rate of theophylline monohydrate under various conditions agreed well with predictions based on the Extended Simu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600750515
更新日期：1986-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.09.020
更新日期：2016-12-01 00:00:00
abstract：:The purpose of this work was to study the permeability of two relatively lipophilic sulfenamide prodrugs of linezolid (clogP 0.85), N-(phenylthio)linezolid (1, clogP 2.77) and N-[(2-ethoxycarbonyl)ethylthio]linezolid (2, clogP 1.43), across Caco-2 cell monolayers. Both prodrugs were found to convert to linezolid in th...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23084
更新日期：2012-09-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980026c
更新日期：1998-10-01 00:00:00
abstract：:In an attempt to explain the mechanism of protein stabilization conferred by detergents, we investigated the effect of Tween 80 on aggregation of bovine serum albumin (BSA) using circular dichroism (CD) and native gel electrophoresis. CD thermal scans showed that BSA denatures at about 54 degrees C in 20 mM Tris, pH 7...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/(SICI)1520-6017(200005)89:5<646::AID-JPS10
更新日期：2000-05-01 00:00:00
abstract：:The P-glycoprotein (Pgp), a drug efflux pump, is expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics. In inflammatory bowel disease, a dysregulation in the production of tumor necrosis factor (TNF)alpha and interferon (IFN)gamma, and an alteration of Pgp expression and activity...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20072
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.22409
更新日期：2011-05-01 00:00:00
abstract：:Two polymorphs of the 1:1 fumarate salt of 1,4-diazabicyclo[3.2.2]nonane-4-carboxylic acid 4-bromophenyl ester, developed for the treatment of cognitive symptoms of schizophrenia and Alzheimer disease, have been characterized. The 2 crystal structures have been solved, and their phase relationships have been establish...
journal_title：Journal of pharmaceutical sciences
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更新日期：2011-12-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671132
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更新日期：2009-10-01 00:00:00
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更新日期：2021-02-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640909
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abstract：:Application of low-frequency ultrasound has been shown to enhance transdermal transport of drugs (low-frequency sonophoresis). In this paper, we show that the efficacy of low-frequency ultrasound in enhancing transdermal transport can be further increased by its combination with sodium lauryl sulfate (SLS), a well-kno...
journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670839
更新日期：1978-08-01 00:00:00
abstract：:The application of low-frequency ultrasound enhances drug transport through the skin, a phenomenon referred to as low-frequency sonophoresis. This enhancement is mediated through cavitation, the formation and collapse of gaseous bubbles. We hypothesized that the efficacy of low-frequency sonophoresis can be significan...
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更新日期：2002-03-01 00:00:00
abstract：:The plasma protein binding of drugs has been shown to have significant effects on the quantitative relationship between clinical pharmacokinetics and pharmacodynamics. In many clinical situations, measurement of the total drug concentration does not provide the needed information concerning the unbound fraction of dru...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20558
更新日期：2006-08-01 00:00:00
abstract：:Incorporation of starch USP or a modified cornstarch within the granules of several drug formulations was investigated. In general, the formulation containing the modified starch exhibited improved processing characteristics as well as improved tablet properties. A comparison of a granulated and a direct compression f...
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doi：10.1002/jps.2600640231
更新日期：1975-02-01 00:00:00
