The Role of the Geometric Configuration of Diethylaminoethanol Derivative in the Pharmaceutical Development of a Dosage Form Based on It

Abstract

Introduction. A comprehensive study of the active pharmaceutical ingredient (API) molecule is one of the defining criteria for pharmaceutical development according to the Quality by Design (QbD) concept and the ICH Q8 framework. The spatial arrangement of atoms in the molecule often has a significant impact on the physicochemical and technological properties of API, and hence on the method of producing dosage form based on it.Aim. To study some properties of substances, geometrical isomers of the molecule, which is a derivative of diethylaminoethanol (DEAE), as well as to compare the selected technologies for the preparation of dosage form.Materials and methods. The objects of the study were two substances, spatial isomers of the molecule, a derivative of DEAE, possessing neuroprotective, antiastenic and antioxidant effects. The study of properties of API and the obtained tablets was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV edition, the Pharmacopoeia of the Eurasian Economic Union, as well as the European Pharmacopoeia 9.0 edition. In this research were used substances that have not expired at the time of the study, as well as authorized for medical use.Results and discussion. The geometrical configuration of the DEAE derivative influences the properties of the API, which has an impact on the stages of pharmaceutical development, especially on the development of the technology and formulation of dosage form. The use of cis-DEAE significantly simplifies the technological process and improves the quality of the resulting drug, and as a consequence, better stability and longer shelf life of dosage form may be achieved.Conclusion. In the course of the study, some properties of cis-DEAE API were studied and compared with similar properties of trans-DEAE. A comparison of tablet preparation technologies based on the two mentioned configurations of the DEAE derivative molecule has been carried out. It was found that the isomers have different technological properties and also differ significantly in moisture adsorption capacity. This property determines the approach to tablet preparation. The technology of tablets based on cis-DEAE appears to be simpler, and dosage form based on it is more stable.

Keywords

• geometric configuration
• isomerism
• hygroscopicity
• solid dispersed systems
• wet granulation
• direct compression