dc.contributor.author | O'BRIEN, JOHN EUGENE | |
dc.contributor.author | HEALY, ANNE MARIE | |
dc.contributor.author | TAJBER, LIDIA | |
dc.contributor.author | CORRIGAN, OWEN | |
dc.contributor.author | MC CABE, THOMAS | |
dc.contributor.author | PALUCH, KRZYSZTOF | |
dc.date.accessioned | 2011-02-14T17:13:13Z | |
dc.date.available | 2011-02-14T17:13:13Z | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011 | en |
dc.identifier.citation | Paluch, K.J., Tajber, L., McCabe, T., O'Brien, J.E., Corrigan, O.I. and Healy, A.M., Preparation and characterisation of novel chlorothiazide potassium solid-state salt forms: intermolecular self assembly suprastructures, European Journal of Pharmaceutical Sciences, 42, 3, 2011, 220-229 | en |
dc.identifier.other | Y | |
dc.identifier.uri | http://hdl.handle.net/2262/50547 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Chlorothiazide (CTZ) is a poorly soluble diuretic agent. The aim of the present work was to produce and characterise a potassium salt form of chlorothiazide which has the potential advantages of improved aqueous solubility and potassium supplementation. A number of novel potassium salt forms of CTZ (CTZK) were prepared: CTZK monohydrate (form I), CTZK dihydrate (form II), anhydrous CTZK (form III), CTZK monohydrate hemiethanolate (form IV) and a desolvate of CTZK monohydrate hemiethanolate (form V). These salt forms were characterised by thermal analysis, PXRD, NMR, elemental analysis, FTIR, Karl Fisher titrimetry, ICP-MS and GC-MS. The ethanol-free CTZK forms were also characterised by dynamic vapour sorption analysis (DVS). CTZK form I was stable (in the DVS) over the range 0% to 60% RH. The dihydrate form of the salt was stable (in the DVS) over a broader range of relative humidities, 10 to 90%RH at 25?C. CTZK form II was less hygroscopic at high humidities (70-90% RH) than the previously reported CTZNa dihydrate. Single crystal X-ray analysis indicated that chlorothiazide potassium, crystallised from water or water/acetone mixture, formed a dihydrated polymeric-like intermolecular self-assembly (ISA) suprastructure. The ISA coordination was determined to be: (CTZ)3?K?(H2O)2(CTZ)2?(H2O)2?K?(CTZ)3 (monoclinic, space group: C2/c, single crystal cell parameters: a = 18.328(4) ?, b = 7.3662(16) ?, c = 19.993(5) ?, ?= 90?, ?= 99.729(3)?, ? = 90?). When CTZK was crystallised from ethanol, a monohydrate hemiethanolate ISA was formed, described as (CTZ)3?K?CTZ?(H2O)2?CTZ?K?(CTZ)2 (triclinic, space group: P-1, single crystal cell parameters: a = 7.078(3) ?, b = 9.842(5) ?, c = 21.994(11) ?, ? = 87.522(13)?, ?= 84.064(14)?, ?= 78.822(12)?). The aqueous solubility of CTZK dihydrate, was determined to be 78.71 ? 1.82 mg/ml, approximately 400-fold higher than chlorothiazide, indicating a biopharmaceutical advantage associated with the potassium salt form. | en |
dc.description.sponsorship | The authors wish to acknowledge funding for this research from the Irish Research Council for Science
and Engineering Technology (IRCSET) and the Solid State Pharmaceutical Cluster (SSPC), supported
by Science Foundation Ireland under grant number [07/SRC/B1158].
Authors would like to thank Professor Brian McMurry for scientific consultation of single crystal data
and Mr. Adam Coburn University College Dublin, Department of Chemistry, for elemental analysis. | en |
dc.format.extent | 220-229 | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.relation.ispartofseries | European Journal of Pharmaceutical Sciences; | |
dc.relation.ispartofseries | 42; | |
dc.relation.ispartofseries | 3; | |
dc.rights | Y | en |
dc.subject | Pharmacology and pharmacy | en |
dc.subject | Chlorothiazide potassium | en |
dc.title | Preparation and characterisation of novel chlorothiazide potassium solid-state salt forms: intermolecular self assembly suprastructures | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Irish Research Council for Science Engineering and Technology | en |
dc.contributor.sponsor | Science Foundation Ireland | |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/paluchk | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/jeobrien | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/healyam | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ltajber | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ocorrign | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/tmccabe | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/paluchk | |
dc.identifier.rssinternalid | 69826 | |
dc.identifier.rssuri | http://dx.doi.org/10.1016/j.ejps.2010.11.012 | en |