Abstract
The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials—ASTM E698, Friedman and Flynn–Wall–Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.
Highlights
Candesartan is a selective, potent, and competitive antagonist of AT1 receptor (Angiotensin II receptor type 1) that is part of angiotensin II (Ang II) receptor blocker’s (ARBs) family of drugs [1,2].Candesartan is a selective, potent, and competitive antagonist of AT1 receptor (Angiotensin II receptor type 1) that is part of angiotensin II (Ang II) receptor blocker’s (ARBs) family of drugs [1,2]
Tita et al reported on the thermal behavior of candesartan, active substance and in pharmaceutical compounds in a dynamic nitrogen atmosphere in non-isothermal conditions, but they did so without mentioning any data regarding the strength of investigated pharmaceutical formulations and without clearly indicating if candesartan or candesartan cilexetil were studied as pure active pharmaceutical ingredient (API); the paper mentions the cilexetil prodrug, but, though the chemical structure of the drug corresponds to candesartan, it does not correspond to the cilexetil derivative [37]
We investigat7edoft1h7e solid-state stability of perindopril erbumine as a pure API and of perindopril erbumine in a pharmaceutical formulation, and we showed that the used excipients osfhaousoldlidbpehuasrmedacienutniecawllfyo-rdmeuvlealtoiponed, agneinne-driecpstohlikdinpehtiacrmstuacdeyuctaicnalrefovremaluiflatthioenesxcbiepciaeuntssedtheteeyrmcoinnteritbhuetiendcrteoaasne oinrctrheeadseedcrtehaesremoaflsstatabbiliiltiyty oof fCpCeraifntedroiptsriilnecrobrupmorianteio[n58in]. a tablet
Summary
Candesartan is a selective, potent, and competitive antagonist of AT1 receptor (Angiotensin II receptor type 1) that is part of angiotensin II (Ang II) receptor blocker’s (ARBs) family of drugs [1,2]. Tita et al reported on the thermal behavior of candesartan, active substance and in pharmaceutical compounds in a dynamic nitrogen atmosphere in non-isothermal conditions, but they did so without mentioning any data regarding the strength of investigated pharmaceutical formulations and without clearly indicating if candesartan or candesartan cilexetil were studied as pure APIs; the paper mentions the cilexetil prodrug, but, though the chemical structure of the drug corresponds to candesartan, it does not correspond to the cilexetil derivative [37]
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