Abstract：
PURPOSE:To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. METHODS:Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissolution kinetics of spray-dried dispersions were studied under sink and non-sink conditions. BMS-A supersaturation was studied in the presence of pre-dissolved PVP-VA and HPMC-AS. Potency and crystallinity of undissolved solid dispersions were determined by HPLC and DSC. Polymer dissolution kinetics were obtained by mass balance calculation. Bioavailability of solid dispersions was assessed in dogs. RESULTS:In solid state, both polymers are miscible with BMS-A, while PVP-VA solublizes the drug better. BMS-A dissolves similarly from both solid dispersions in vitro regardless of dissolution method, while the HPMC-AS dispersion performed much better in vivo. At the same concentration, HPMC-AS is more effective in prolonging BMS-A supersaturation; this effect was negated by the slow dissolution rate of HPMC-AS. Further study revealed that fast PVP-VA dissolution resulted in elevated drug loading in undissolved dispersions and facilitated drug recrystallization before complete release. In contrast, the hydrophobicity and slower HPMC-AS dissolution prevented BMS-A recrystallization within the HPMC-AS matrix for >24 h. CONCLUSIONS:The lower bioavailability of PVP-VA dispersion was attributed to BMS-A recrystallization within the undissolved dispersion, due to hydrophilicity and fast PVP-VA dissolution rate. Polymer selection for solid dispersion development has significant impact on in vivo performance besides physical stability.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Qian F,Wang J,Hartley R,Tao J,Haddadin R,Mathias N,Hussain Mdoi
10.1007/s11095-012-0695-7subject
Has Abstractpub_date
2012-10-01 00:00:00pages
2765-76issue
10eissn
0724-8741issn
1573-904Xjournal_volume
29pub_type
杂志文章abstract：PURPOSE:The in-situ particle size of delavirdine mesylate in dry mix and tablets was determined. METHODS:Optical microscopy and fluorescence microscopy combined with image analysis were used for qualitative and quantitative measurements. RESULTS:Using optical microscopy, it was demonstrated qualitatively that fragmen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018875130152
更新日期：1999-04-01 00:00:00
abstract：PURPOSE:The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. METHODS:In vivo activity was investigated using six volunteers by determining the reduction in colony form...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
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abstract：PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial ...
journal_title：Pharmaceutical research
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doi：10.1007/s11095-006-9568-2
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T c...
journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-012-0691-y
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-010-0127-5
更新日期：2010-07-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1023/a:1012127829032
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journal_title：Pharmaceutical research
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更新日期：1997-03-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1085-5
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journal_title：Pharmaceutical research
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pub_type： 杂志文章
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更新日期：1988-01-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
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更新日期：2014-07-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2013-05-01 00:00:00
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pub_type： 杂志文章
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