Rational excipient selection for co-amorphous formulations.
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.
a School of Pharmacy , University of Eastern Finland , Kuopio , Finland.
Ossi
O
Korhonen
a School of Pharmacy , University of Eastern Finland , Kuopio , Finland.
Katja
K
Pajula
a School of Pharmacy , University of Eastern Finland , Kuopio , Finland.
Riikka
R
Laitinen
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D012995:Solubility
D005079:Excipients
Co-amorphous; interaction parameter; interactions; miscibility; molecular modeling; solubility parameter; stability