Neusilin Impregnation Improves Amorphization and Dissolution of Poorly Soluble Drugs

Achievement date: 
2015
Outcome/accomplishment: 

Researchers at the Center for Structured Organic Particulate Systems (C-SOPS), a National Science Foundation (NSF) Engineering Research Center (ERC) based at Rutgers University in partnership with New Jersey Institute of Technology, Purdue University, and the University of Puerto Rico-Mayaguez, have proven that neusilin—a readily available, commercial class of porous excipients—offers a viable solution for stabilizing amorphous drug forms. The C-SOPS ERC scientists have successfully shown that neusilin can enable adsorption in or on mesoporous materials to offer a means of improving water-solubility of some drugs.

Impact/benefits: 

One of the most important challenges to novel drug development is the fact that poorly soluble drugs commonly have low and variable oral absorption rates. The high internal energy of the amorphous drug state relative to the crystalline state causes increases in solubility and dissolution rates and can enhance bioavailability of drug treatments.The experimental work at the CSOPS-ERC establishes a working proof of concept for converting crystalline drugs to highly stable amorphous forms, thereby enabling improved dissolution of poorly water-soluble drugs.

Explanation/Background: 

Amorphous drug forms offer a potential solution to circumvent the issue of solubility and dissolution-limited bioavailability of some pharmaceuticals. There are several methods developed for preparing amorphous active pharmaceutical ingredients (APIs) such as: melt quenching, ball milling, hot melt extrusion, spray drying, and others. Each method has advantages and limitations. The amorphous state also holds the risk of converting back to the energetically more favorable crystalline state during processing or storage.

 

Although a variety of very specialized and proprietary chemically different mesoporous materials have been found in the literature, very limited information has been available on the use of neusilin for enhancing bioavailability of poorly water-soluble drugs by amorphization. X-ray powder diffraction analysis revealed that the neusilin-impregnated drug, fenofibrate itraconazole (FNB/ITZ), was amorphous. There was no crystalline peak observed in the impregnated drug. There was no crystalline peak observed after 4 weeks of storage at 40 °C, 75% RH. The resulting amorphous states of each of the two drugs appear to be physically stable during storage. Amorphous FNB/ITZ exhibited a higher dissolution rate than the as-received crystalline drug (USP II, 50 rpm, 7.2 mg/ml SDS, 48 mg drug).