Thermal Analysis as a Useful Tool in Drug-Excipient Compatibilty Studies: The Impact in Pharmaceuticals Products

Abstract

This mini-review discusses the importance of thermal analysis as a predictive tool for pharmaceutical stability in the design of drug-excipient compatibility studies. In this regard, aspects regarding the need for preformulation studies recommended by the FDA were discussed, revealing thermo analytical techniques such as TGA / DTG and DSC as rapid analyses, with little sample consumption and reliable responses. The main idea of this expert opinion is to show the need for drug-excipient compatibility studies and their impacts on the efficacy, toxicity and stability of pharmaceutical products that can be readily identified through the tools cited herein. Thus, drug-excipients compatibility studies are encouraged as predictors of the stability of the final pharmaceutical product.

Drug–Drug Compatibility Evaluation of Sulfasalazine and Folic Acid for Fixed-Dose Combination Development Using Various Analytical Tools

“…The TG/DTA measurements of SASP and FA were done on a 1:1 binary mixture to increase the intensity of the possible reactions and for a better visualization of the incompatibility [ 19 ]. The TG/DTA curves of SASP, FA and the SASP/FA blend are shown in Figure 3 .…”

“…The incompatibility of two drugs can result in the change of their physical characteristics, which can be observed as a shift in the characteristic peak temperature (±5 °C) or if the peak notably changes its shape, disappears or a new peak occurs [ 12 , 19 , 21 , 22 ]. In the provided measurements, a shift of the peak temperature was observed for SASP (9.6 °C); on the other hand, the FA characteristic melting peak did not shift notably (1.6 °C), which implies that the two drugs might be compatible.…”

Ispitivanje fizikalno-kemijske kompatibilnosti lijekova primjenom analitičkih tehnika: pregled istraživanja razvoja fiksne kombinacije 5-aminosalicilata i folne kiseline

“…Međutim, da bi se pojačao intenzitet mogućih reakcija te ostvarila bolja vizualizacija promjena, zbog niske osjetljivosti navedenih instrumenata, poželjno je pripremati smjese u omjeru 1 : 1. 43,45 Potencijalne interakcije u takvim sustavima mogu se pratiti kao pomaci specifičnih pikova, poput endotermnih pikova tališta, kao i promjene u entalpijama u dobivenim termogramima smjesa u odnosu na termograme čistih sastavnica. 38,[46][47][48] Iako nedostaju službeni kriteriji koji definiraju nekompatibilnost sastavnica, najčešće se prati pomak karakterističnog pika tališta, pri čemu se pomak veći od 5,0 °C smatra značajnom promjenom koja ukazuje na potencijalnu interakciju sastavnica.…”

Stay calm and focus on the learning outcomes: Tools for taking biophysical chemistry online

“…In this lab, students detect incompatibilities between a drug and an excipient through thermal analysis techniques. [1][2][3][4] After a short introduction to the relevant techniques, groups of 3 to 4 members are given previously collected data. They are asked to analyze the data for drug stability, thermal behavior of the binary mixtures (drug-excipient), and compare the drug-excipient data with the one from the drug and excipients alone.…”

“…For online delivery, this goal is rewritten as: “ Analyze data obtained from various repositories to calculate physical properties of materials and communicate results in clear scientific writing .” For example, the “ Drug‐excipient interactions ” experiment was redesigned for distance learning following goal #6. In this lab, students detect incompatibilities between a drug and an excipient through thermal analysis techniques 1–4 . After a short introduction to the relevant techniques, groups of 3 to 4 members are given previously collected data.…”