Rational excipient selection for co-amorphous formulations

ABSTRACT

Introduction: For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability issues of many small molecule drugs. Since the amorphous form is a high energy and unstable state of solid matter, any material in that form requires stabilization.

Areas covered: This review examines the technologies being exploited to stabilize the amorphous state in co-amorphous formulations. The review emphasizes the importance of the appropriate selection criteria of stabilizing excipient and focuses on the mechanisms of stabilization.

Expert opinion: An extensive literature review has revealed that the current research seeking to achieve stabilization of an amorphous form tends to be conducted on a case-by-case basis. This kind of approach is very inefficient since it can rarely be transferred to other cases. The greatest weakness in the selection of stabilizing excipient for co-amorphous formulations is that modern computational tools have rarely been utilized as a predictive tool in the selection of the excipient. It is evident that more research needs to be done to study larger datasets with modern in silico tools, chemometrics and advanced statistical tools to achieve a more predictive, and systematic approach for the screening of stabilizing excipients to be incorporated into co-amorphous formulations.

KEYWORDS:

• Co-amorphous
• interactions
• miscibility
• molecular modeling
• solubility parameter
• interaction parameter
• stability

Article highlights

• The article provides a comprehensive overview on the current status of development of co-amorphous formulations

• The emphasis is placed on finding optimal ways for the selection of the small molecule combinations

• The article demonstrates the apparent lack of systematic selection methods, capable for managing large datasets, for the co-amorphous combinations

• Examples of the possible future directions regarding more systematic (in silico) approaches are given in the form of case studies

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.