Dissolution and precipitation of dipyridamole: Effect ofpH and bile salt concentration.
dc.contributor.author | Mithani, Sabena Dawoodali | |
dc.contributor.advisor | Rodriguez-Hornedo, Nair | |
dc.date.accessioned | 2016-08-30T17:39:00Z | |
dc.date.available | 2016-08-30T17:39:00Z | |
dc.date.issued | 1998 | |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9825307 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/131054 | |
dc.description.abstract | The effects of pH and sodium taurocholate (STC) concentrations, at values encountered in the gastrointestinal tract in the fasted and fed states, on the solubility, kinetics and mechanism of dissolution, and precipitation of dipyridamole (a typical example of a poorly soluble weak base) have been investigated. The solubilization capacity of STC for ionized dipyridamole molecules is greater than for the nonionized molecules. Disk dissolution experiments indicate that the dissolution is diffusion-controlled, The disk and paddle intrinsic dissolution rates of dipyridamole increase with decrease in pH and increase in STC concentration. However, the dissolution rate (DR) enhancement does not parallel the solubility enhancement. At 15 mM STC, decrease in dipyridamole diffusivity decreases the disk DR. Improved wetting increases the DR of dipyridamole powder in the presence of STC. In the absence of STC, limited wetting of DPM agglomerates results in a lower DR enhancement with decrease in pH. The DR was also determined by monitoring the crystal size distribution and solution concentration of dipyridamole during dissolution. The effect of agitation intensity suggests that particles less than 15 $\mu$m in diameter exhibit surface-controlled dissolution, whereas larger particles undergo diffusion-controlled dissolution. At 15 mM STC, the dependence of DR on undersaturation is very weak at pH 6.5, whereas at pH 5.5 this dependence changes from linear to parabolic with decrease in undersaturation. The surface characteristics of dipyridamole crystals during dissolution are related to the hydrogen bond networks along the different crystal faces. Metastability zone widths and induction times for precipitation have been determined as in vitro indicators for the potential of precipitation of dipyridamole in vivo. A four-tank mixing-tank model was used to predict dipyridamole concentrations in the small intestine. There is a potential for precipitation of dipyridamole at pH and taurocholate concentrations representative of the fasted state but not the fed state. 5 mM STC inhibits whereas 15 mM STC promotes dipyridamole precipitation. Changes in the crystal morphology are observed in the presence of taurocholate. The kinetics and morphology of growth are explained on the basis of intermolecular interactions at the crystal faces. | |
dc.format.extent | 266 p. | |
dc.language | English | |
dc.language.iso | EN | |
dc.subject | Bile | |
dc.subject | Concentration | |
dc.subject | Concentrationsalt | |
dc.subject | Dipyridamole | |
dc.subject | Dissolution | |
dc.subject | Effect | |
dc.subject | Ph | |
dc.subject | Precipitation | |
dc.subject | Salt | |
dc.title | Dissolution and precipitation of dipyridamole: Effect ofpH and bile salt concentration. | |
dc.type | Thesis | |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Health and Environmental Sciences | |
dc.description.thesisdegreediscipline | Pharmaceutical sciences | |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/131054/2/9825307.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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