Reducing the Sublimation Tendency of Ligustrazine through Salt Formation

Abstract

Two new salts of ligustrazine (tetramethylpyrazine, TMP) with the sweeteners saccharine (SAC) and acesulfame (ACS) have been synthesized through the anion exchange reaction. Single crystals of the new forms were prepared, and their structures were determined. The stability of the new salts against heat and humidity was tested and compared to the commercial hydrochloride and phosphate salts. The sublimation kinetics at various temperatures was analyzed using the Arrhenius equation. The results indicated that TMP-ACS exhibits significantly reduced sublimation tendency and hygroscopicity, which make it a more suitable salt for developing a tablet with acceptable shelf stability than the salts currently used in commercial products.

Drug–Drug Cocrystallization Simultaneously Improves Pharmaceutical Properties of Genistein and Ligustrazine

“…The sublimation tendency of TMP could be reduced by forming sweet salts with saccharine and acesulfame. 44 The weight loss of GEN-TMP was 0.19% under identical conditions. Therefore, the cocrystallization between GEN and TMP substantially stabilizes TMP against sublimation.…”

“…However, GEN-TMP cocrystal showed a unique PXRD pattern which was distinct from those of GEN and TMP. New peaks emerged at 2θ values of 6.4°, 21.8°, and 31.1° indicating the presence of a new crystalline phase. , The absence of characteristic peaks of both GEN and TMP suggests the complete consumption of both reactants. The PXRD pattern simulated from the single-crystal structure of GEN-TMP matched well with the experimental pattern (Figure ).…”

“…Both commercial forms of TMP, a hydrochloride salt and a phosphate salt, readily sublime under ambient condition. , In this study, almost half of TMP (49.03%) was lost after 24 h at 25 °C, confirming the earlier reports (Figure ). The sublimation tendency of TMP could be reduced by forming sweet salts with saccharine and acesulfame . The weight loss of GEN-TMP was 0.19% under identical conditions.…”

“…GEN exhibited characteristic crystalline peaks at 2θ values of 7.5°, 14.6°, 15.9°, and 23.2°, whereas TMP exhibited characteristic new crystalline phase. 43,44 The absence of characteristic peaks of both GEN and TMP suggests the complete consumption of both reactants. The PXRD pattern simulated from the singlecrystal structure of GEN-TMP matched well with the experimental pattern (Figure 2).…”

Profoundly improved photostability of dimetronidazole by cocrystallization

“…15,16 The changes in molecular packing after cocrystallization affect the physicochemical properties of an API. For examples, cocrystallization has been used to change drug solubility, [17][18][19][20] bioavailability, 15,21,22 permeability, 23,24 physical and chemical stability, [25][26][27] and taste. 23,28 We note that not all changes are pharmaceutically favourable.…”