Physico-chemical properties of two anhydrous azathioprine forms and their interaction with typical pharmaceutical excipients: highlighting new findings in drug formulation development

Abstract

The physico-chemical properties of two anhydrous AZA forms and their interaction with typical pharmaceutical excipients were assessed by applying various methods (such as PXRD, HPLC, TG/DSC, IR, Raman, PL or UV-Vis) in order to highlight new directions for drug formulation. The stability assessment of AZA anhydrous forms I and II was performed in order to determine the risk of degradation of the active ingredient by accidental exposure to nonstandard conditions in the industrial environment, under different storage, transport or processing conditions. The benefits of form II include increased resistance to chemical degradation over a wide range of pH, but further control of storage and processing conditions is necessary to avoid polymorphic transformation into form I. The solubility assessment on the AZA solid forms in different environments that simulate the conditions of the gastrointestinal tract has the advantage of a significantly increased solubility of form II compared with the commercial form I due to the modification of the crystalline structure. In the case of capsules compared to AZA form I or II as powder, an improvement in their solubility was observed, promoted by the presence of one or more excipients in the formulation mixture.

Keywords:

• Azathioprine
• anhydrous forms
• stability
• solubility
• excipients compatibility
• capsule

Acknowledgments

The authors would like to thank Chem. Dumitru Samohvalov, research scientist at Sara Pharm Solutions, for his technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded in the frame of project co-funded by the European Regional Development Fund under the Competitiveness Operational Program 2014–2020 entitled “Physico-chemical analysis, nanostructured materials and devices for applications in the pharmaceutical field and medical in Romania”, the financing contract no. 58/05.09.2016 signed of National Institute of Materials Physics with National Authority for Scientific Research and Innovation as an Intermediate Body, on behalf of the Ministry of European Funds as Managing Authority for Operational Program Competitiveness (POC), the sub-contract of the D type, no. 4529/29.11.2017, signed of National Institute of Materials Physics with S.C. Sara Pharm Solutions S.R.L.