Amorphous solid dispersions of polysaccharide-drug nanoparticles were produced by a rapid precipitation process known as flash nanoprecipitation and the formulation process and properties of nanoparticles were investigated. In this thesis, several novel cellulose derivatives and a pullulan derivative were studied. Among these polymers, carboxymethyl cellulose acetate butyrate (CMCAB)-drug nanoparticles were investigated in detail. Previous work has shown that the presence of different chemical groups in CMCAB could aid in complexation with hydrophobic drugs with low solubility, forming an amorphous matrix which can increase the effective solubility and, hence, bioavailability of the drug in physiological conditions. An antibacterial drug and two less soluble anti-viral drugs were selected as model drugs for this study. A separate study was conducted with several other cellulose derivatives like cellulose acetate propionate adipates with two different degree of substitution 0.33 and 0.85 (CAP-Adp 0.33 and CAP-Adp 0.85), cellulose acetate sebacate (CA-320S Se) and butyl pullulan-6-carboxylate (BPC) polymers. The effect of polymer interaction with drug molecule on release of antiviral drugs was studied with these latter polymers.
The purpose of this research was two-fold. First, the methodology for producing drug-polymer nanoparticles with well-defined particle size distributions was developed. Second, the factors affecting drug loading and release properties of these nanoparticles were investigated. The nanoparticles were processed using two methods of solvent removal and drying to investigate their effects on drug loading and particle size: (a) various combinations of rotary vacuum evaporation (rotavap) and acid-induced flocculation were used and (b), dialysis followed by freeze drying. Dynamic light scattering showed particle sizes were between 150-400 nm with polydispersity index values as low as 0.12. The antibiotic drug loading efficiencies ranged from 14-40%, whereas drug loading efficiency as high as 85 % was attained with the antiviral drug. The dissolution studies showed an increase in the solution concentration and release of the amorphous drug nanoparticles. The high glass transition temperature helped to stabilize the drug in an amorphous form, thus increasing the effective solution concentration of the drug in an aqueous medium. / Ph. D.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/23692 |
| Date | 08 August 2013 |
| Creators | Mazumder, Sonal |
| Contributors | Learning Sciences and Technologies, Davis, Richey M., Sriranganathan, Nammalwar, Edgar, Kevin J., Joseph, Eugene Gregory, Riffle, Judy S. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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