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dc.contributor.authorWoodhull, Margaret Brewster
dc.date.accessioned2012-04-20T20:01:17Z
dc.date.available2012-04-20T20:01:17Z
dc.date.issued1995
dc.identifier.urihttp://hdl.handle.net/10713/1472
dc.descriptionUniversity of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 1995en_US
dc.description.abstractThe intermolecular relationship governing the conformational change of the polyanhydride poly(carboxyphenoxypropane-sebacic acid){dollar}\sb{lcub}20:80{rcub}{dollar}, (poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar}) in both solution and solid state was investigated and related to the drug delivery of specifically chosen drugs from a poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} matrix. The occurrence of conformational change, the underlying factors which induce change, and the ultimate impact of conformational change on poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} degradation and drug release were investigated in order to develop a fundamental basis by which formulations and processes could be developed to produce reliable and effective polyanhydride dosage forms. Solution studies carried out in methylene chloride, chloroform, tetrahydrofuran, and dioxane revealed that both the conformation and degradation of poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} were solvent-dependent. Infrared studies in the carbonyl stretching region (1830-1730 cm{dollar}\sp{lcub}-1{rcub}{dollar}) indicated that a stronger polymer-solvent interaction occurred in the chlorinated solvent solutions due to hydrogen-bonding with the carbonyl oxygens. The solutions exhibiting stronger polymer-solvent interactions produced a more expanded conformation determined by intrinsic viscosity studies. Degradation of the polyanhydride linkage was conducted using methanol (2.5%w/v) as the degradative reactant and quantified by an absorbance decrease in the anhydride asymmetric stretch (1815 cm{dollar}\sp{lcub}-1{rcub}{dollar}). The rate of poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} degradation was faster in chloroform and methylene chloride than that in tetrahydrofuran and dioxane. The effect of solvent on degradation was due either to electron-withdrawing or conformational differences between the solvent types. The conformational behavior of poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} in the solid state was evaluated by differential scanning calorimetry (DSC) and infrared analysis of the carbonyl stretching region. At temperatures above 30{dollar}\sp\circ{dollar}C and below the melting point, the polymer was shown to undergo time-dependent conformational changes resulting in increased heats of fusion and melting points. The change in thermal behavior was attributed to hydrogen-bonding detected by an increased infrared shift in the carbonyl stretch associated with the carboxylic acid end group of a poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} film treated at 40, 50, and 60{dollar}\sp\circ{dollar}C.;The effect of drug type and temperature on drug release from a poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} matrix was evaluated by flow cell analysis. Salicylic acid and salicylamide were chosen as model drugs due to their similarity in chemical structure with the exception that salicylic acid had a greater potential for hydrogen bonding due to a carboxylic acid side group. Both drugs exhibited a decrease in drug release with increased dwell temperatures of 40, 50 and 60{dollar}\sp\circ{dollar}C. The release profiles of salicylamide were less affected than salicylic acid, possibly due to hydrogen-bonding differences within the matrix. The salicylic acid release profile was profoundly decreased after storage at 37{dollar}\sp\circ{dollar}C for 12 and 24 hours indicating that drug release may be retarded or prevented due to conformational changes at physiological temperatures. The understanding of the role of temperature and hydrogen-bonding in polyanhydride conformation is recommended as a critical component to the development of a stable poly(CPP-SA){dollar}\sb{lcub}20:80{rcub}{dollar} dosage form.en_US
dc.language.isoen_USen_US
dc.subjectChemistry, Pharmaceuticalen_US
dc.subjectChemistry, Polymeren_US
dc.subjectHealth Sciences, Pharmacyen_US
dc.titleInvestigation of the conformational change in a polyanhydride system and its effect on drug deliveryen_US
dc.typedissertationen_US
dc.contributor.advisorHollenbeck, R. Gary
dc.identifier.ispublishedYes
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