東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Physicochemical characterization of ...

Dutta, Asish K.

Linked to FindBook

Google Book

Amazon

博客來

Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state./
Author:	Dutta, Asish K.
Description:	599 p.
Notes:	Adviser: Christy M. Wyandt.
Contained By:	Dissertation Abstracts International67-12B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3246006

Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state.
Dutta, Asish K.

Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state. - 599 p.

Adviser: Christy M. Wyandt.

Thesis (Ph.D.)--The University of Mississippi, 2006.

The purpose of this research was to determine the solution-state physicochemical characteristics of NPC 1161 C, a novel anti-malarial 8-aminoquinoline derivative, and to study its complexation characteristics in solution state with hydroxylpropyl-beta-cyclodextrin (HPBCD) and sulfobutylether-beta-cyclodextrin (SBEBCD). To facilitate the physicochemical characterization of the drug, a stability-indicating reversed-phase HPLC method was developed and validated according to ICH guidelines. The impurities present in the drug were identified using FT-ICR-MS. The drug was found to decompose with acid, dry heat, oxidation and reduction; however, it was stable in the presence of base. The major solution-state physicochemical parameters of the drug determined include pKa, octanol-water partition coefficient, aqueous and pH solubility, cosolvency, and pH stability. Preliminary solid-state studies of the drug included thermal analysis using differential scanning calorimetry and thermogravimetric analysis and hygroscopicity studies. Thermal analysis revealed that in the solid-state, the drug is present as semi-crystalline powder, which transforms into the amorphous state upon melting. The drug was also found to sublimate at higher temperatures. The complexation characteristics of the drug with HPBCD and SBEBCD determined included solubility analysis, thermodynamic properties of complexation using isothermal titration calorimetry (ITC), and structural characterization of the inclusion complexes using NMR-spectroscopy and molecular modeling techniques. Solubility analysis revealed a significant increase in solubility with either cyclodextrin in aqueous media of various pH. A 1:1 stoichiometry of binding was observed in all the cases. The binding affinity of the various ionic species of the drug with SBEBCD was found to be higher than that with HPBCD, and was also found to differ on binding with the same cyclodextrin; BH+ species was found to have significantly larger binding constants than the BH22+ species with both HPBCD and SBEBCD. The driving forces for binding, as obtained from ITC, were found to be primarily hydrophobic, and van der Waals interactions with HPBCD and predominantly electrostatic interactions with SBEBCD. NMR spectroscopy, molecular docking and molecular dynamics studies revealed that different binding affinities for the various species of the drug were primarily due to different binding modes of those species with the cyclodextrins.Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state.
LDR:03420nam 2200265 a 45 001 964115
005 20110901
008 110901s2006 eng d
035 $a (UMI)AAI3246006
035 $a AAI3246006
040 $a UMI $c UMI
100 1 $a Dutta, Asish K. $3 1287183
245 1 0 $a Physicochemical characterization of NPC 1161C, an 8-aminoquinoline anti-malarial drug, and its inclusion complexes with cyclodextrins in solution state.
300 $a 599 p.
500 $a Adviser: Christy M. Wyandt.
500 $a Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7029.
502 $a Thesis (Ph.D.)--The University of Mississippi, 2006.
520 $a The purpose of this research was to determine the solution-state physicochemical characteristics of NPC 1161 C, a novel anti-malarial 8-aminoquinoline derivative, and to study its complexation characteristics in solution state with hydroxylpropyl-beta-cyclodextrin (HPBCD) and sulfobutylether-beta-cyclodextrin (SBEBCD). To facilitate the physicochemical characterization of the drug, a stability-indicating reversed-phase HPLC method was developed and validated according to ICH guidelines. The impurities present in the drug were identified using FT-ICR-MS. The drug was found to decompose with acid, dry heat, oxidation and reduction; however, it was stable in the presence of base. The major solution-state physicochemical parameters of the drug determined include pKa, octanol-water partition coefficient, aqueous and pH solubility, cosolvency, and pH stability. Preliminary solid-state studies of the drug included thermal analysis using differential scanning calorimetry and thermogravimetric analysis and hygroscopicity studies. Thermal analysis revealed that in the solid-state, the drug is present as semi-crystalline powder, which transforms into the amorphous state upon melting. The drug was also found to sublimate at higher temperatures. The complexation characteristics of the drug with HPBCD and SBEBCD determined included solubility analysis, thermodynamic properties of complexation using isothermal titration calorimetry (ITC), and structural characterization of the inclusion complexes using NMR-spectroscopy and molecular modeling techniques. Solubility analysis revealed a significant increase in solubility with either cyclodextrin in aqueous media of various pH. A 1:1 stoichiometry of binding was observed in all the cases. The binding affinity of the various ionic species of the drug with SBEBCD was found to be higher than that with HPBCD, and was also found to differ on binding with the same cyclodextrin; BH+ species was found to have significantly larger binding constants than the BH22+ species with both HPBCD and SBEBCD. The driving forces for binding, as obtained from ITC, were found to be primarily hydrophobic, and van der Waals interactions with HPBCD and predominantly electrostatic interactions with SBEBCD. NMR spectroscopy, molecular docking and molecular dynamics studies revealed that different binding affinities for the various species of the drug were primarily due to different binding modes of those species with the cyclodextrins.
590 $a School code: 0131.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0419
690 $a 0572
710 2 0 $a The University of Mississippi. $3 1019522
773 0 $t Dissertation Abstracts International $g 67-12B.
790 $a 0131
790 1 0 $a Wyandt, Christy M., $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3246006