Related Experiment Video
Updated: Mar 28, 2026

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
A Strategy for Co-former Selection to Design Stable Co-amorphous Formations Based on Physicochemical Properties of
Hiroshi Ueda1,2, Noriyuki Muranushi3, Satoshi Sakuma3
1Physicochemical and Preformulation, Applied Chemistry and Analysis, Research Laboratory for Development, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka, 561-0825, Japan. hiroshi.ueda@shionogi.co.jp.
Purpose:
This study aimed to investigate the physicochemical factors contributing to stable co-amorphous formations and to design a co-former selection strategy.
Methods:
Non-steroidal inflammatory drugs were used as main components and/or co-formers. Physical mixtures of the materials were melted. Co-amorphization was characterized by the inhibition effect of the co-former on crystallization of the main component from the undercooled melt. The contribution of physicochemical factors to the co-amorphous formation was analyzed by multivariate analysis. Co-amorphous samples prepared by melting were subjected to thermal and spectroscopic analyses and the isothermal crystallization test.
Results:
Naproxen (NAP) was employed as the main component having a rapid crystallization tendency. Some materials used as the co-former inhibited the crystallization of amorphous NAP; decreasing melting temperatures of the components was an indicator of co-amorphization. The contribution of some physicochemical features (e.g., crystallization tendency, glass transition temperature (Tg)/melting temperature and molecular flexibility) of the co-formers to a co-amorphous formation was suggested by multivariate analysis. Deviation of the glass transition temperature from the theoretical value and changes in the infrared spectra of the co-amorphous samples were correlated with intermolecular interaction. The crystallization behaviors of the co-amorphous samples depended on their Tg.
Conclusions:
The results showed a relationship between stable co-amorphous formation and the physicochemical features of the components, which should inform efficient co-former selection to design stable co-amorphous formations.
Related Concept Videos
Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Formulation and Manufacturing Process: Physical Attributes of Generic Tablets and Capsules
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Biopharmaceutical Factors Influencing Drug Product Design: Overview

