February 8th, 2022

We are proud to announce that our latest manuscript “Physico-chemical properties of two anhydrous azathioprine forms and their interaction with typical pharmaceutical excipients: highlighting new findings in drug formulation development” was accepted by Drug Development and Industrial Pharmacy. Preformulation studies, as a first and proactive step in rational drug formulation development, play an important role in anticipating formulation issues and identifying realistic paths in dosage form technology. In order to develop a stable, effective and safe dosage form, its investigations are designed to establish the physico-chemical, physico-mechanical properties of drug substances, excipients and packaging materials. As different types of polymorphs exhibit different physicochemical properties in terms of solubility, stability or therapeutic activity, the purpose of this paper is to present an evaluation of the physicochemical properties of two anhydrous AZA forms and their interaction with typical pharmaceutical excipients. Potential interactions between excipients and AZA can lead to alteration in physico-chemical stability of dosage form. Compared with the already known oral AZA tablet form (known as Imuran or Azasan), an alternative that sustained a prolonged gastric residence was studied, as such new capsule formulations were proposed and manufactured. Such modifications in the delivery system are needed to overcome the disadvantages associated with oral tablet form and to provide drugs of higher selectivity for medical treatment. In comparison with available Imuran or Azasan tablet composition, using lactose or lactose monohydrate as a major excipient, in the current work the stability of AZA forms I and II in the presence of another common excipient non-hygroscopic, chemically stable, with good flow properties and high compressibility is evaluated. Moreover, for those patients with lactose intolerance, another stable composition can be an exciting finding in AZA formulation development. On the other hand, considering the sensitivity of AZA Form II to humidity, different excipients combination and mixture compositions are tested in order to identify the suitable and stable drug formulation for both anhydrous AZA forms. The stability of AZA Form II in the presence of D-Mannitol is shown through experimental data consisting of the application of several techniques (such as, PXRD, TG/DSC, FT-IR, FT-Raman). The detailed results of the study can be read here: https://doi.org/10.1080/03639045.2022.2032131 and we hope you will find it interesting.


This work was supported by the Romanian grant POC 2014-2020, Priority axis 1 – A1.2.3-G, 4529/2017 (AMD-FARMA-MED-RO) carried out in collaboration with National Institute of Materials Physics.