Ligustrazine (or Tetramethylpyrazine, TMP) is an active pharmaceutical ingredient that faces the challenges of bitter taste and low oral bioavailability by the commercial phosphate salt (TMP-Pho). We tackled these challenges by forming salts with two sweeteners, acesulfame (Acs) and saccharine (Sac). Both salts effectively masked the bitter taste of TMP. Compared to TMP-Pho, TMP-Sac shows 43% lower solubility and 11% lower permeability while TMP-Acs shows higher (two-fold) solubility but 24% lower permeability. Both TMP-Acs and TMP-Sac exhibited approximately 40% higher bioavailability through reducing the rate of TMP absorption. Thus, salt formation with both sweeteners simultaneously addressed the challenges brought about by the bitter taste and lower bioavailability of TMP.
Bibliographical noteFunding Information:
This work was supported by grants from National Natural Science Foundation of China (No. 31872508 ), Natural Science Foundation of Hebei (No. C2017204085 ), and Key Research grants of Hebei ( 19227505D ).
© 2020 Elsevier B.V.
PubMed: MeSH publication types
- Comparative Study
- Journal Article