Date of Award
1-1-2018
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
Department
Pharmaceutics and Drug Delivery
First Advisor
Michael A. Repka
Second Advisor
Chalet Tan
Third Advisor
S. Narasimha Murthy
Relational Format
dissertation/thesis
Abstract
Although salt formation is the most ubiquitous and effective method of increasing the solubility and dissolution rates of acidic and basic drugs, it consumes large quantities of organic solvents and is a batch process. Herein, we show that the dissolution rate of indomethacin (a poorly water-soluble drug) can be increased by using hot melt extrusion of a 1:1 (mol/mol) indomethacin:tromethamine mixture to form a highly crystalline salt, the physicochemical properties of which are investigated in detail. Specifically, pH–solubility studies demonstrated that this salt exhibited a maximal solubility of 19.34 mg/mL (>1000 times that of pure indomethacin) at pH 8.19. A solvent evaporation technique was also used for salt formation. Spectroscopic analyses (infrared, nuclear magnetic resonance) of both methods; demonstrated, in situ salt formation with proton transfer. Powder X-ray diffraction and differential scanning calorimetry confirmed the crystalline nature of salts formed in both methods. Even though a number of amorphous salts of acidic drugs have been reported, the formation of a crystalline salt of an acidic drug by hot melt extrusion is completely unprecedented, which makes this study an important benchmark for the pharmaceutical production industry.
Recommended Citation
Bookwala, Mustafa, "Crystalline Salt Formation of an Acidic Drug Indomethacin Using Hot Melt Extrusion Technology" (2018). Electronic Theses and Dissertations. 1340.
https://egrove.olemiss.edu/etd/1340
Concentration/Emphasis
Emphasis: Pharmaceutics