Date of Thesis
The solubility of a solid dosage pharmaceutical is crucial to its bioavailability and success as a medication. The amorphous phase of a molecule, formed through processing techniques with or without polymer excipients, can have higher solubility in the body. Multiple methods exist to create a single phase amorphous system. Mechanical processing methods, such as milling, present a possible alternative to the industrial standards of spray drying and hot melt extrusion. This study investigates a novel mechanical processing method called solid-state shear pulverization (SSSP) with model crystalline ingredients lactose, sucrose, and adipic acid. The effect of the type of small organic molecule, the addition of polymer excipient, and the role of shear stress applied to the sample are studied using this method. All samples processed using SSSP maintain partial crystalline character. However, certain samples such as pure sucrose and lactose also exhibit amorphous character when processed. When co-processed, interactions between excipient and crystalline ingredient affects the amount of amorphous material formed. Increased reductions in crystallinity are observed when sucrose is blended with PVP, an amorphous polymer excipient, compared to when sucrose is processed alone. The shear imparted by the screws can also change material properties during processing, as is exhibited by the adipic acid and PVP mixture. This sample has unique behavior and further investigation of its material properties is recommended to explore the interactions between excipients and crystalline molecules.
solid-state shear pulverization (SSSP), adipic acid, sucrose, lactose, polyvinylpyrrolidone (PVP), amorphous
Honors Thesis (Bucknell Access Only)
Bachelor of Science in Chemical Engineering
Warfel, Katherine Frances, "Mechanical Activation of Small Crystalline Organic Molecules Using Solid-State Shear Pulverization" (2017). Honors Theses. 402.