Dissertation/Thesis Abstract

Stabilization of the Amorphous Form of Poorly Soluble Drugs Using Ethyl Cellulose in Solid Dispersions
by Abhyankar, Hrishita, M.S., University of the Sciences in Philadelphia, 2017, 55; 10692990
Abstract (Summary)

The aims of this research was to evaluate the partial crystallinity of two BCS class II drugs (Ketoconazole and Chlorpropamide) when prepared as solid-dispersions with three viscosity grades of Ethyl -Cellulose (EC7, EC45, or EC100 cP). Two processes were explored for preparing the dispersions; namely, spray drying, and, co-precipitation induced by non-solvent addition. The partial crystallinity of the formulations was evaluated using Differential Scanning Calorimetry, with crystal enthalpy values of 103.4 J/G for Ketoconazole and 98.8 J/G for Chlorpropamide (from literature). Both formulation processes yielded free-flowing white powders with a size range of 3 to 49 μm. Control formulations with no EC content showed crystal enthalpies ranging from 83-97%, suggesting practically no amorphous stabilization in the absence of Ethyl Cellulose. The co-precipitation process was ineffective in preparing amorphous formulations for Ketoconazole, as crystal enthalpies ranged from 82-100%. For Chlorpropamide, however, the efficiency of the co-precipitation process improved with the viscosity grade of the Ethyl Cellulose, with EC7, EC45, and EC100 showing % crystalline enthalpies of 98, 76, and 51% respectively. The progressive decrease in crystal enthalpies suggested a corresponding increase in the amorphous forms of these drugs. Spray-dried formulations prepared with EC7 showed practically no crystalline enthalpies for both Ketoconazole and Chlorpropamide, suggesting that these drugs were almost entirely trapped in their amorphous state, and would expect to show higher solubility upon dissolution. Overall, this research shows that spray-drying with low viscosity grade Ethyl Cellulose such as EC7 is an optimal approach for the preparation of amorphous solid-dispersions of BCS Class II drugs.

Indexing (document details)
Advisor: Jonnalagadda, Sriramakamal
Commitee: Gupta, Pardeep, Schaefer, Frederick T., Wigent, Rodney J.
School: University of the Sciences in Philadelphia
Department: Pharmaceutical Sciences
School Location: United States -- Pennsylvania
Source: MAI 57/02M(E), Masters Abstracts International
Source Type: DISSERTATION
Subjects: Pharmaceutical sciences
Keywords: Amorphous, Cellulose, Dispersions, Drugs, Ethyl, Solid, Soluble, Stabilization
Publication Number: 10692990
ISBN: 9780355414745
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