The effect of formulation and processing variables on the stability of levothyroxine sodium tablets /
Patel, Himanshu
The effect of formulation and processing variables on the stability of levothyroxine sodium tablets / Himanshu Patel ؛committee chair adel sakr. - 144 pages : illustrations ; 30 cm.
Includes abstract
Thesis (Ph.D.)--University of Cincinnati, 2003
Includes bibliographical references
Abstract: These series of experiments were devised to
study the effects of various formulation and processing
variables on the stability of levothyroxine. The studies
were performed with levothyroxine drug substance (powder
or solution), excipient slurries with levothyroxine at
50ʻC and tablet-incorporated levothyroxine under ICH
accelerated stability conditions. Additionally, stability
of tablets manufactured by wet granulation and / or direct
compression at different compression pressures was
evaluated under ICH accelerated stability conditions. It
was found that the active, levothyroxine, was stable when
stored for six months at 40ʻC/75% Relative Humidity (RH)
in open or closed containers; also, it was non-hygroscopic
under normal operating conditions (>30%RH). In diluent
slurries when stored at 50ʻC for one month, levothyroxine
was more stable at pH 11 than at pH 3. Levothyroxine
tablets manufactured with dibasic calcium phosphate or
mannitol and stored under accelerated stability conditions
met USP assay requirements at three months, but not at six
months. Tablets manufactured with lactose anhydrous,
starch, and microcrystalline cellulose failed to meet USP
requirements at three months. After six months at
accelerated stability conditions, tablets manufactured
with basic pH modifiers had less than 5% loss in potency,
and thus, they met USP assay requirements. Therefore, it
was concluded that excipients used in the manufacture of
levothyroxine tablets affected levothyroxine stability.
The use of desiccant for while storing levothyroxine
tablets, didn't appear to affect their stability at ICH
accelerated stability conditions. Furthermore, the use of
basic pH modifiers is a technique for improving tablet-
incorporated levothyroxine stability. After 3 months
storage at ICH accelerated stability conditions the
tablets manufactured by wet granulation or direct
compression did not show significant difference in
stability. Thus, the type of manufacturing method does not
influence the stability of levothyroxine tablets,
manufactured with / without sodium carbonate and using
dibasic calcium phosphate as diluent. Interestingly, it
was found that the initial assay value of levothyroxine
tablets (compressed at 2000 and 6000 lbs) was lower than
that of the uncompressed granules/powder. Thus tablet
compression appears to affect the stability of
levothyroxine. It was concluded that formulation and
processing variables affect the stability of levothyroxine
tablets
levothyroxine sodium--medicine
615.1 / P.H.E
The effect of formulation and processing variables on the stability of levothyroxine sodium tablets / Himanshu Patel ؛committee chair adel sakr. - 144 pages : illustrations ; 30 cm.
Includes abstract
Thesis (Ph.D.)--University of Cincinnati, 2003
Includes bibliographical references
Abstract: These series of experiments were devised to
study the effects of various formulation and processing
variables on the stability of levothyroxine. The studies
were performed with levothyroxine drug substance (powder
or solution), excipient slurries with levothyroxine at
50ʻC and tablet-incorporated levothyroxine under ICH
accelerated stability conditions. Additionally, stability
of tablets manufactured by wet granulation and / or direct
compression at different compression pressures was
evaluated under ICH accelerated stability conditions. It
was found that the active, levothyroxine, was stable when
stored for six months at 40ʻC/75% Relative Humidity (RH)
in open or closed containers; also, it was non-hygroscopic
under normal operating conditions (>30%RH). In diluent
slurries when stored at 50ʻC for one month, levothyroxine
was more stable at pH 11 than at pH 3. Levothyroxine
tablets manufactured with dibasic calcium phosphate or
mannitol and stored under accelerated stability conditions
met USP assay requirements at three months, but not at six
months. Tablets manufactured with lactose anhydrous,
starch, and microcrystalline cellulose failed to meet USP
requirements at three months. After six months at
accelerated stability conditions, tablets manufactured
with basic pH modifiers had less than 5% loss in potency,
and thus, they met USP assay requirements. Therefore, it
was concluded that excipients used in the manufacture of
levothyroxine tablets affected levothyroxine stability.
The use of desiccant for while storing levothyroxine
tablets, didn't appear to affect their stability at ICH
accelerated stability conditions. Furthermore, the use of
basic pH modifiers is a technique for improving tablet-
incorporated levothyroxine stability. After 3 months
storage at ICH accelerated stability conditions the
tablets manufactured by wet granulation or direct
compression did not show significant difference in
stability. Thus, the type of manufacturing method does not
influence the stability of levothyroxine tablets,
manufactured with / without sodium carbonate and using
dibasic calcium phosphate as diluent. Interestingly, it
was found that the initial assay value of levothyroxine
tablets (compressed at 2000 and 6000 lbs) was lower than
that of the uncompressed granules/powder. Thus tablet
compression appears to affect the stability of
levothyroxine. It was concluded that formulation and
processing variables affect the stability of levothyroxine
tablets
levothyroxine sodium--medicine
615.1 / P.H.E