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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

THE RELATIONSHIPS AMONG FLORY-HUGGINS SPECIFIC INTERACTION PARAMETERS, MAXIMUM AMORPHOUS CAPACITY, SOLID-STATE INTERACTIONS, EQUILIBRIUM SOLUBILITY, AND DISSOLUTION OF SPRAY DRIED AMORPHOUS DRUG DISPERSIONS

Freed, Peter, 0000-0002-9565-8168 January 2021 (has links)
The aim of this study is to evaluate the specific interactions, solid-state, and solution-state interactions between drug and polymers in amorphous spray dried dispersions and evaluate the subsequent impact on drug dissolution in non-sink media. This is intended to be used as a screening tool for dosage-form development. Formulations with specific theoretical and observed interactions between drug and polymer may exhibit improved dissolution rate, increased absorption rate, increased capacity for drug loading and improved physical stability. Four BCS II class drugs were evaluated: ibuprofen, ketoprofen, nifedipine, and itraconazole. Binary and ternary spray dried dispersions were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between each drug and polymer were determined using theoretical group contribution calculations and DSC data. Solid-state interactions were evaluated using modulated DSC and FTIR, and solution-state interactions were evaluated using 1H-NMR. The maximum amorphous content for each formulation was calculated from the enthalpy of melting point peaks using DSC. Flory-Huggins Specific Interaction Parameters were calculated and show that a negative specific parameter was associated with increased solid-state interactions and improved capacity to contain drug in the amorphous state. Correlations between Flory-Huggins specific interaction parameter, amorphous drug loading, and equilibrium solubility were established. Ternary spray-dried dispersions containing drug, conventional polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary spray-dried dispersions. Solid and solution-state interactions observed in binary systems may be incorporated into ternary systems with arabinogalactan to both maintain amorphous drug capacity and improve dissolution rate compared to the binary. Supersaturation of amorphous binary and ternary dispersions was attained as compared to the crystalline drug. Mechanical properties of polymers as related to dissolution rate were investigated, and ternary systems containing to rapidly swelling and dissolving arabinogalactan had more pronounced erosion properties as compared to binary drug : HPMC dispersions. The resultant ternary systems are an improvement over binary drug polymer systems. / Pharmaceutical Sciences

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