Crystalline Salt Formation of an Acidic Drug Indomethacin Using Hot Melt Extrusion Technology

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.

Name thesis:degree_name

M.S. in Pharmaceutical Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Pharmaceutics and Drug Delivery

Year dc:date.available

2018

Author dc:creator

• Bookwala, Mustafa

Contributors dc:contributor

• Michael A. Repka
• Chalet Tan
• S. Narasimha Murthy

• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://egrove.olemiss.edu/etd/1340

OAI identifier oai:identifier

oai:egrove.olemiss.edu:etd-2339