반응 #1840932

ord-c84bc55e6f3a4b618da68af6a954cd31

반응 방정식

N[C@@H](Cc1cc(I)c(Oc2ccc(O)c(I)c2)c(I)c1)C(=O)O
liothyronine
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
N[C@@H](Cc1cc(I)c(Oc2cc(I)c(O)c(I)c2)c(I)c1)C(=O)[O-].O.[Na+]
levothyroxine sodium
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
N[C@@H](Cc1cc(I)c(Oc2cc(I)c(O)c(I)c2)c(I)c1)C(=O)[O-].O.[Na+]
levothyroxine sodium
N[C@@H](Cc1cc(I)c(Oc2cc(I)c(O)c(I)c2)c(I)c1)C(=O)O
levothyroxine

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타at 40° C.
  2. 2
    기타at 25° C.

실험 절차

FIG. 2 depicts graphs of liothyronine (T3) impurity over time at 40° C. for compositions containing 100 μg (“mcg”), 200 μg or 500 μg levothyroxine sodium (L), and either 3 mg or 10 mg mannitol (M). FIG. 3 depicts graphs of T3 impurity over time at 25° C. for compositions containing 100 μg, 200 μg or 500 μg levothyroxine sodium, and either 3 mg or 10 mg mannitol. The graphs in FIGS. 2 and 3 for the compositions containing 3 mg mannitol (open symbols) correspond to the results listed in Table 2. The graphs in FIGS. 2 and 3 for the compositions containing 10 mg mannitol (closed symbols) correspond to results of an analysis of the stability of levothyroxine in solid compositions containing 100 μg, 200 μg or 500 μg levothyroxine sodium and 10 mg mannitol. These solid compositions were formed by combining water, the levothyroxine sodium, the mannitol, and 500 μg dibasic sodium phosphate to form liquid mixtures, and then adding sodium hydroxide to provide a pH of about 11.8. Water for injection (USP) was added to each liquid mixture as needed to provide total volumes of 1 mL. The liquid mixtures were lyophilized to provide solid compositions, which were then stored in vials at temperatures of 25° C. or 40° C. The stability of the levothyroxine in the solid compositions over time at different temperatures was determined by measuring the amount of T3, as described above. The results of these measurements for the compositions containing 10 mg mannitol are listed in Table 3, below.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09168239B2uspto-grants-2015_10