자료유형  

 학위논문

Control Number  

0016935126

International Standard Book Number  

9798380489591

Dewey Decimal Classification Number  

541

Main Entry-Personal Name  

Deac, Alexandru.

Publication, Distribution, etc. (Imprint  

[S.l.] : Purdue University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(324 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

General Note  

Advisor: Taylor, Lynne S.;Zhang, Geoff G.Z.

Dissertation Note  

Thesis (Ph.D.)--Purdue University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약The dissolved concentration of an active pharmaceutical ingredient in biological fluids is of significant importance for establishing a therapeutic effect in patients. However, the current pharmaceutical landscape is abundant in poorly soluble drugs that require solubility enhancing techniques to enable their administration. A promising technique, with increasing commercial success, is to molecularly mix drug and polymer to create an amorphous solid dispersion (ASD). While these mixtures provide enhanced drug solubility and dissolution in aqueous solutions, the mechanistic processes by which they release drug into solution are not well understood. Some unexplained behaviors include rapid drug release even at the maximum supersaturated concentration and spontaneous formation of drug-rich nanoparticles. These are beneficial for rapidly achieving and maintaining a highly supersaturated drug concentration during absorption, if crystallization is inhibited. However, the phenomena occur at typically low drug loading and are abruptly lost above a certain threshold termed the 'limit of congruency' (LoC), which has been reported to vary based on the drug-polymer system. In this research, the mechanisms underpinning ASD release at low and high drug loading were studied, and the factors affecting LoC were mechanistically explored by performing dissolution experiments and utilizing imaging, separation, thermal analysis, and spectroscopy methods to characterize the materials in the presence and absence of water. The results show that ASDs developed a gel layer on the surface when exposed to aqueous solution. This water-rich environment was thermodynamically unstable and phase separated into hydrophilic and hydrophobic phases. The morphology of the hydrophobic phase was directly related to the ASD release behavior, where ASDs below the LoC exhibited a dispersed and stable hydrophobic phase morphology, and ASDs above the LoC displayed a continuous or aggregated morphology. In cases where thermodynamic factors were rate limiting, LoC was inferred from features on the ternary phase diagram. Moreover, drug-polymer interactions and polymer molecular weight were demonstrated to affect the morphology of the hydrophobic phase and ultimately the LoC. The conclusions from this work provide the basis of a theoretical framework for rationally designing ASDs and optimizing their release.

Subject Added Entry-Topical Term  

Aqueous solutions.

Subject Added Entry-Topical Term  

Polymers.

Subject Added Entry-Topical Term  

Humidity.

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Thermodynamics.

Subject Added Entry-Topical Term  

Viscosity.

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Spectrum analysis.

Subject Added Entry-Topical Term  

Nanoparticles.

Subject Added Entry-Topical Term  

Pharmaceuticals.

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Solvents.

Subject Added Entry-Topical Term  

Microscopy.

Subject Added Entry-Topical Term  

Drugs.

Subject Added Entry-Topical Term  

Particle size.

Subject Added Entry-Topical Term  

Molecular weight.

Subject Added Entry-Topical Term  

Hydration.

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Interfaces.

Subject Added Entry-Topical Term  

Analytical chemistry.

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Chemistry.

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Nanotechnology.

Subject Added Entry-Topical Term  

Optics.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Polymer chemistry.

Added Entry-Corporate Name  

Purdue University.

Host Item Entry  

Dissertations Abstracts International. 85-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643654