Document Type


Date of Award

Fall 1-31-2011

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)


Chemical, Biological and Pharmaceutical Engineering

First Advisor

Marino Xanthos

Second Advisor

Costas G. Gogos

Third Advisor

Boris Khusid

Fourth Advisor

Laurent Simon

Fifth Advisor

Ecevit Atalay Bilgili

Sixth Advisor

Kun S. Hyun

Seventh Advisor

Michael Chien-Yueh Huang

Eighth Advisor

Peng Wang


This dissertation contains the results of three related novel investigations in the field of structure-property-processing relationships of pharmaceutical polymer-based products. They are: a) modification of a pharmaceutical anionic nanoclay with two different Active Pharmaceutical Ingredients (APIs) to produce nanohybrid API carriers intended to be used alone or in acrylic polymer matrices, b) comparison of binary systems containing the above APIs in the selected acrylic polymers in terms of their miscibilities with the polymer, but in the absence of nanoclay, and c) comparison of the polymer/API binary systems with ternary polymer/API/Clay systems.

For the first study, the calcination method which can be directly applied to carbonated hydrotalcite was used and successfully achieved API intercalations. During reconsitution of the clay, the crystalline APIs in the clay interlayer was apparently transformed in an amorphous state, and as a result it showed increased apparent solubility in the simulated body fluids.

The second study dealt with API-polymer miscible or immiscible systems prepared by different mixing methods. The selected APIs have low solubility at the low pH of the aqueous medium and different solubility parameters by comparison with the polymer. The Eudragit® E100/ DIK-Na+ mixture produced by batch melt mixing showed an API solid dispersion whereas the Eudragit® E100/ IND system produced an API solid solution. These different morphologies were anticipated by calculating API and polymer solubility parameters and were confirmed by several analytical methods. The miscible API-polymer system showed better apparent solubility in the aqueous media. In order to confirm the effect on apparent solubility of the different API physical states differing in particle size or crystallinity, solvent casting and twin screw extruder mixing were also compared with batch mixing. The amorphous API in the polymer matrix showed improved apparent solubility as compared to its crystalline state. This confirmed that the state of API in the polymer matrix is the most important factor to increase its apparent aqueous solubility.

The third segment of this research focused on the API release from the ternary system (API/clay/polymer) produced by hot melt mixing. A novel approach in order to have a sustained API release by utilizing the nanoclays was attempted. Since the API present in the clay interspacing may experience one more step in its release by diffusion as compared to the binary system, the API from the ternary system showed a slower and more controlled release than the one from the binary system. Controlled API release from such a ternary system produced by hot melt mixing, to the best of our knowledge, has not been reported in the literature.

The mechanisms of APIs release in solution from the aforementioned systems were identified by using the Korsmeyer-Peppas (Power law) and Peppas-Sahlin models.



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