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dc.contributor.authorHahm, Huijeong Ashley
dc.date.accessioned2012-03-30T20:27:53Z
dc.date.available2012-03-30T20:27:53Z
dc.date.issued2002
dc.identifier.urihttp://hdl.handle.net/10713/1147
dc.descriptionUniversity of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 2002en_US
dc.description.abstractOptimizing the use of the super disintegrants (SD) requires a better understanding of their mechanism of action than currently exists. Because their functionality is fundamentally related to the ability to draw liquid into tablet matrices, it was hypothesized that higher initial moisture contents from sorbed water would decrease their ability to effect rapid disintegration. In testing this hypothesis, a device that automatically measures disintegration time was designed and constructed, sensitive tests to evaluate disintegrant efficiencies were developed, and the mechanisms of action of SDs were studied by relating several physical changes caused by sorbed moisture to their ability to disintegrate tablets. AcDiSolRTM PolyplasdoneRTM XL, and PrimojelRTM, representative of different classes of SDs, were studied. The effect of sorbed water on plasticity, tablet tensile strength, x-ray powder diffraction pattern, and morphology were evaluated. A slowly disintegrating partially soluble tablet matrix was designed based on artificial neural network and statistical experimental design models and employed with the USP disintegration apparatus. With increasing moisture content, all SDs were plasticized and their tablets exhibited lower tensile strength. No change in morphology was apparent for AcDiSolRTM stored at relative humidities up to 75.3% at room temperature, but PrimojelRTM particles agglomerated. Upon compression with sand, AcDiSolRTM and PrimojelRTM particles did not appear to have deformed, but PolyplasdoneRTM XL particles agglomerated. Except for AcDiSolRTM, SDs stored at higher humidity caused slower disintegration of anhydrous lactose tablets. Disintegration times were slower when SDs with higher water content were incorporated in the designed slowly-disintegrating tablet matrix. The automatic disintegration test apparatus was found suitable for evaluating the disintegration of rapidly disintegrating tablets and enabled the determination of whether tablet disintegration was predominantly controlled by diffusion or interfacial separation. This device also enabled the systematic design and evaluation of tablet matrices for fast disintegration in the mouth suitable for oral administration of drugs to patients unable to swallow tablets. SDs exhibited different physical and functional sensitivities to sorbed moisture. In general, AcDiSolRTM was found to be the least sensitive and the most effective disintegrant. The mechanism of tablet disintegration was dependent both on the SD and the nature of the tablet matrix.en_US
dc.language.isoen_USen_US
dc.subjectChemistry, Pharmaceuticalen_US
dc.titleEffect of sorbed water on the efficiency of super disintegrants: Physical and mechanistic considerationsen_US
dc.typedissertationen_US
dc.contributor.advisorAugsburger, Larry L.
dc.identifier.ispublishedYes
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